Gynecology Lectures PDF

Oraganization and summarization of gynaecology lectures The followings are all gynaecology lectures taken in stage 5 1. Primary amenorrhea 2. Secondary amenorrhea 3. Dysmenorrhea & PMS 4. PCOS 5. Assisted reproduction (IVF) 6. Contraception 7. Abnormal uterine bleeding 8. Endometriosis...

Oraganization and summarization of gynaecology lectures The followings are all gynaecology lectures taken in stage 5 1. Primary amenorrhea 2. Secondary amenorrhea 3. Dysmenorrhea & PMS 4. PCOS 5. Assisted reproduction (IVF) 6. Contraception 7. Abnormal uterine bleeding 8. Endometriosis & Adenomyosis 9. Fibroids 10. Cervical disorders 11. Endometrial cancer These topics are explained in details same 12. Vulval & Vaginal diseases as lecture, with some additional notes 13. Benign ovarian diseases 14. Ovarian cancer It start from primary amenorrhea and 15. Genital tract infection 16. Subfertility end with genital prolapse (in order) 17. Male infertility 18. Menopause 19. Urinary incontinence 20. Genital prolapse 21. Hyperandrogenism 22. Anomalies These four topics not explained 23. Disorders of sexual development in this file 24. Gynaecological surgeries Prepared by Rayan Anwar Thanks for Halder Jamal  Primary amenorrhea Amenorrhea could be physiological or pathological Physiological as pre puberty, menopause, pregnancy and lactation Pathological (primary and secondary) Primary amenorrhea: no menses by 14 without SSC or 16 with SSC. #1 is constitutional, #2 is turner, #3 is MRKHS. Outflow obstruction leads to retrograde menses and endometriosis. If SSC present: Imperforate hymen (hematocolpos/metra, cyclical pain, bluish bulging hymen + abdominal mass, difficult urination or defecation) Transverse vaginal septum (3 levels, same as above but normal hymen, pink bulge) Vaginal + cervix agenesis (hematometra, cyclical pain but not bulge and no abdominal mass bcs there is no vagina) Absent vagina and non-functioning uterus: normal female genitalia but blind-ending vaginal dimple, this is known as Mayer-Rokitansky- Kuster-Hauser (MRKH) syndrome, uterine development absent, 40% have renal anomalies e.g absent kidney, and skeletal abnormalities CAIS Resistant ovary syndrome (elevated level of gonadotrophin in the presence of normal ovarian tissue, absence or malfunction of FSH receptors in the ovarian follicles) Constitutional delay (immature GnRH pulse, don't need treatment, can confirm by a trial of COCP that leads to withdrawal bleeding) If no SSC (Hypogonadism): Normal stature: Hypogonadotropic: 1. Congenital (isolated GnRH↓ or Kallmann if there is anosmia) 2. Acquired (weight loss/anorexia, exercise, hyperprolactinemia), these are more likely to cause secondary amenorrhea. Hypergonadotropic: 1. Gonadal (xx or xy) agenesis 2. Gonadal dysgenesis (turner mosaic or other x deletions/mosaics) 3. Ovarian failure (CTX, RTX) 4. Galactosemia Short stature Hypogonadotropic: 1. Hydrocephalus (from infection) 2. Head (basal skull) trauma 3. Tumors (Craniopharyngioma) 4. Empty sella syndrome (congenital absence of pituitary) Hypergonadotropic: Turner or other x deletions/mosaics Diagnosis History Developmental milestones (age of growth spurt ,age of thelarche, adrenarche) Congenital infection, Trauma, Tumor Cyclic symptoms of menstruation Weight changes. Excessive exercise History of anosmia General examination (Height, weight, SSC) Pelvic examination Investigation Hormonal investigations should include LH, FSH, prolactin ,oestradiol and testosterone levels Ultrasound (determine presence, state and size of ovaries and any follicular activity, uterine size) Rarely laparoscopy to assess pelvic organs. Treatment depends on underlying cause e.g Complete agenesis of vagina by Vaginal reconstruction prior to or soon after marriage. Chromosomal Abnormality Turner or other types of gonadal dysgenesis, short term use of combination of estrogen and progestogen. Gonads of XY gonadal dysgenesis should be removed for its increased development of seminoma or dysgerminoma. In androgen insensitivity syndrome, ectopic gonads are removed after SSC are well-developed, because they may turn to malignancy  Secondary amenorrhea Secondary amenorrhea: cessation of menstruation for more than six months in a normal female of reproductive age that is not due to pregnancy, lactation or menopause. Secondary amenorrhea: no menses for 3 months if regular or 6 months if irregular cycles. Causes Hypothalamic (hypogonadotrophic hypogonadism): functional amenorrhea (COCP advised), weight loss, exercise, chronic illness, psychological distress, idiopathic. Regular menstrual cycle will not occur if BMI is 5 days Younger than normal age at menarche, (Early menarche) Cigarette smoking Causes of secondary dysmenorrhea Uterine fibroid, endometriosis, adenomyosis, PID, chronic pelvic congestion, IUD, asherman syndrome, cervical stenosis Aetiology 1. Primary dysmenorrhoea is associated with uterine hypercontractility characterized by excessive amplitude and frequency of contractions and a high ‘resting’ tone between contractions. 2. During contractions endometrial blood flow is reduced and there seems to be a good correlation between minimal blood flow and maximal colicky pain. 3. Prostaglandin and leukotriene levels elevated. Clinical presentation Primary dysmenorrhoea appears 6–12 months after menarche when ovulatory cycles begin to become established. early cycles after menarche are usually anovular and tend to be painless Lower abdominal cramp, supra-pubic pain which starts at the onset of menstral flow and lasts 8-72 hours, backache and may be associated with diarrhoea and vomiting. Diagnosis (it is diagnosis of exclusion) If symptoms are typical of primary dysmenorrhoea, treat before considering any examination and investigation especially in adolescents, while if symptoms are atypical do investigation If there is suspicion of secondary dysmenorrhoea TVUS, MRI or laparoscopy should be considered. If symptoms of primary not alleviated with drug secondary causes need to be considered Management Mainstays of treatment are NSAIDs and COCP, the latter especially when fertility control is required Reassurance and explanation NSAIDs: mefenamic acid, naproxen, ibuprofen and aspirin are all effective COCP: act by inhibiting ovulation, decreasing endometrial production of PG, leukotriene by inducing endometrial atrophy, therefore reducing amount of endometrial tissue to produce these mediators. LNG-IUS may be effective for those who have contraindication to NSAIDs or COCP, alternatives include depot progestogens Nonpharmacologic pain management as acupuncture or transcutaneous electrical stimulation (TENS), psychotherapy, hypnosis, and heat patches. Surgical procedures such as presacral neurectomy and uterosacral ligament section Treatment of secondary: treat underlying cause Ibuprofen is preferred analgesic because of its efficacy and safety profiles  PMS PMS: cyclical somatic, psychological and emotional symptoms that occur in the luteal (premenstrual) phase of cycle resolve by the time menses. In 3-9 % occur. Symptoms Depression, irritability, anxiety, tension, aggression, inability to cope and feeling out of control are typical psychological symptoms Bloatedness, mastalgia and headache are classical physical symptoms. Cause Genetic Environmental Psychological & hormonal factors → unusual sensitivity to progesterone due to serotonin deficiency. Conditions which mimic PMS Perimenopause Thyroid disorder Migraine Chronic fatigue syndrome IBS Menstrual disorders Psychiatric disorder (depression, bipolar illness, panic and personality disorder, anxiety) Diagnosis There are no tests to diagnose it Confirmation of luteal phase timing with relief of symptoms by the end of menstruation is diagnostic Treatment 1. Non-medical: exercise, cognitive behavioural therapy, yoga, acupuncture.... 2. Medical: calcium, vitamin E, magnesium, dietary change, vitamin B6, evening primrose oil. SSRI (fluoxetine in luteal phase), cycle suppression (estrogen + mirena, damazol, GnRH ) 3. Surgical: Bilateral oophorectomy with hysterectomy Conclusion Suppression of ovarian cycle eliminates PMS effectively, this can be achieved by GnRH analogues with add back tibolone (type of hormone replacement therapy). Oestrogen also suppresses ovulation and eliminates PMS without menopausal side effects. Intrauterine progestagen (as levonorgestrel IUS) avoid re-stimulation of premenstrual syndrome at the same time that it protects the endometrium.  PCOS PCOS is a syndrome of ovarian dysfunction with 2/3 criteria needed for diagnosis: Hyperandrogenesim (clinical or biochemical), cycle irregularities, PCO on US. It is the most common endocrine disorder in reproductive age Aetiology and pathophysiology Is largely unknown, but seems to involve a complex interaction between environmental (e.g. diet, exercise) and multiple genetic factors. mode of inheritance is autosomal dominant pattern. Factors involved in the pathogenesis of PCOS Dysfunction of ovarian function (↑ ovarian androgens) Dysfunction in hypothalamic function resulting in increased LH → ↑ androgen production by the theca cells Insulin resistance Clinical features Key features include menstrual cycle disturbance, hyperandrogenism and obesity Asymptomatic Oligomenorrhoea/amenorrhoea (related to chronic anovulation) Hirsutism (due to increased level of androgen) Subfertility (anovulatory) Obesity Recurrent miscarriages Acanthosis nigrican Diagnosis History (excess facial hair, acne, increase body weight, previous menstrual irregularity, history of previous miscarriage, FHx of hirsutism and menstrual dysfunction) Examination (weight, hirsutism, acne) Investigation - U/S (at least one ovary with ≥ 12 follicles of 2-9 mm, or ovarian volume > 10 mL if not on OCP) - Serum endocrinology Increase insulin, androgen (testosterone and androstenedione), LH, prolactin, oestradiol, AMH Decrease in sex hormone binding globulin→↑ free androgen index Normal FSH Impaired OGTT, insulin resistance - Laparoscopy: Bilateral polycystic ovaries are characteristic of PCOS - Lipid profile Amenorrhoeic women with PCOS are not oestrogen deficient and are not at risk of osteoporosis. Management (depend on patient complaint) 1- Obesity: diet, exercise, sibutramine, orlistat, (bariatric surgery if BMI >40 or >35 + comorbidities), LAGB. 2- Menses: low dose COCP (first line), alternative is progesterone as provera and mirena, weight loss. provera (for 12 days each 1-3 months or continuous 5-10 mg) 3- Infertility: weight reduction, and induction of ovulation by: anti estrogen (clomiphene), parenteral gonadotropins, laparoscopic ovarian diathermy, wedge resection of the ovary 4- Metformin helps everything except weight (850 bid or 500 tid) baseline investigations should include oral GTT, CBC, urea, electrolytes, and LFT Side effects: gastrointestinal (anorexia, nausea, flatulence and diarrhoea), may be reduced by taking it just before food and gradually increasing the dose. 5- Hirsutism Topical: shaving, electrolysis, waxing, bleaching, laser, photothermolysis, eflornithine. Hormonal: OCP, dianette (ethinylE2 + cyproterone acetate), spironolactone, drosperinone (derivative), previously ketoconazole, finasteride, flutamide (not used bcs of side effects). Drug therapies may take 6–9 months or longer before any improvement of hirsutism is perceived. Ovarian hyper stimulation syndrome OHSS Women with PCOS are at increased risk of developing OHSS. it occur if too many follicles (>10 mm) are stimulated Mechanism is thought to be secondary to activation of ovarian renin-angiotensin pathway and excessive secretion of vascular epidermal growth factor (VEGF). Nausea, vomiting, distension, discomfort, SOB, ascites, effusion, hemoconcentration, VTE. (All worsen by hCG if get pregnant ) Treatment by fluid and heparin. Long term sequelae (complication) Diabetes mellitus Dyslipidaemia Hypertension, cardiovascular disease Endometrial and Breast cancer due to high estrogen Sibutramine is centrally acting agent, serotonin and norepinephrine uptake inhibitor Orlistat is peripherally acting agent, lipase inhibitor Laparoscopic adjustable gastric banding (LAGB) suitable for women with fertility problems, since the band tightness can be varied to accommodate the increased demands of pregnancy when it occurs. Clomiphene (50-100 mg at day 2-6 of bleeding with US to ensure ovulation and singleton, if dose increased >100 rarely confers any benefit and can cause thickening of the cervical mucus, which can impede passage of sperm through the cervix, cumulative dose ↑pregnancy for 10-12 cycles), Parenteral gonadotropins (for patients with anovulatory infertility who are resistant to antioestrogens, start with low dose with US to monitor follicles development) Lap diathermy (no risk of twin or OHSS, no need to monitor by U/S) Wedge resection (cause adhesions so not used nowadays)  Assisted reproduction IVF steps: 1. Controlled Ovarian Stimulation (GnRH ⊕/⊖, FSH, hCG). Close monitoring with TVUS (number/size of follicles & endometrial thickness) and blood estradiol level. We need at least 4, ideally 15 follicles of 18 mm. (To mature many follicles (normally only one mature)) 2. Oocyte Retrieval: under TVUS. Egg removal from mature follicles 3. Oocyte Fertilization: (insemination or ICSI) 4. Embryo Culture: under strict conditions, check fertilization at day 1. 5. Embryo Transfer: at day 5 from fertilisation which is a blastocyst and best time to implant in the uterus, it will undergo lysis at day 7 if you don’t transfer. 6. Luteal phase support IVF is now used for almost all cases of subfertility including tubal disease, endometriosis, failed IUI or where donor eggs are needed Oocyte retrieval (ovum pick up): It’s like a minor surgery, called follicular aspiration. Under TVUS, a needle will be inserted with a guide wire through vaginal wall in to the ovary (should use condom for US and no detergent so that egg will be healthy. Should know anatomy to avoid vein injuries. Aspirate each follicle, and check under microscope if ovum is retrieved or need to wash follicle and aspirate again. With this procedure also the semen from the husband should be prepared. – Should give the husband a sterile cupped container – Should be abstinence from ejaculation for 5 days – Should not use any detergent or lubricant for ejaculation Fertilization: Either by insemination (100000 sperms put in a container with oocyte and waiting for spontaneous fertilization) or ICSI (in which we cat the tail of motile sperm and inject it via a needle to the oocyte, this is to prevent tail movement from damaging ovum DNA. You need to inject it at 90 degree angle to polar body. we can only do ICSI if there is a polar body which means that the ovum has finished meiosis 1) Drugs used in IVF protocols: OCPs:to synchronize the follicles, so that many will grow simultaneously. (To make regular cycles) GnRH⊕/⊖: to down-regulate pituitary so that the ovary would be under our control and not rupture spontaneously (prevents LH surge). Antagonist has a shorter course and less risk of OHSS because it would work immediate unlike agonist which need sometime before it actually inhibit pituitary thus needing a longer course. GnRH agonist as goserelin, buserelin Gonadotropins (FSH): daily injection for 8-10 days. GnRH antagonist as abarelix, degarelix ○ Recombinant FSH (Follistim 200 IU, Gonal-F 75 IU) ○ HMG: extracted FSH from urine of menopausal women (Menopur 75 IU) HCG trigger (ovidrel, novarel 10 000 IU): for final maturation of follicle and timing of oocyte retrieval after about 36-37 hours. You may use GnRH⊕ as trigger if you have used GnRH⊖ to prevent LH surge and estradiol level is high. Estrogen: this is the only one given if you would like to transfer preserved embryos because you don’t need ovarian stimulation here, you just need to prepare endometrium by estrogen and then support luteal phase by progesterone after transference of embryo. Progesterone: for luteal phase support because corpus luteum is inhibited by GnRH⊕/⊖ Ovarian hyperstimulation syndrome (OHSS): a potentially fatal complication of excess stimulation of ovaries by gonadotropins either in IVF or part of ovulation induction for IUI or PCOS treatment that leads to activation of ovarian RAAS & VEGF. Presents with → N&V, abdominal distension and discomfort, breathlessness, ascites, pleural & pericardial effusions, hemoconcentration, VTE, ARDS. (All of them would worsen if pregnancy occurs due to hCG further stimulating the ovaries). Risk of OHSS has been reduced due to: – Low dose stimulation (of FSH) – Using GnRH antagonists instead of agonists – Frequent follow up by US and estradiol levels – Cryopreservation of embryos for future uses which doesn’t require another IVF cycle. 20 1 11 GnRH agonist used for Gonadotrophin is used in first day HCG used and after 7-9 days before Cycle start of cycle till day 11 or 12 follicular size increase e.g 36-37 hours, ovum (long acting) in day 3 (10 mm) pickup is done in day 12 (17 mm) Intrauterine insemination (IUI) is performed by introducing a small sample of prepared sperm into the uterine cavity with fine uterine catheter. most common reasons for IUI are: 1- Low sperm count or decreased spermmobility. 2- Unexplained infertility 3- Hostile cervical condition, including cervical mucos problems 4- Ejaculation dysfunction IUI is not recommended for the following patients: Women who have severe disease of the fallopian tubes Women with history of pelvic infection  Contraception (Family planning) Classification 1. Combined hormonal contraception: COCP, Patches, Vaginal ring. 2. Progestogen-only preparations: POP, Injectables (Depo-provera), Subdermal implants (Implanon). 3. Hormonal emergency contraception: Levonorgestrels, Ulipristal. 4. Intrauterine device: Copper IUD, Hormonal IUD (Mirena). 5. Barrier methods: Condoms, Female barriers, Coitus interruptus, Natural family planning. 6. Sterilization: Female sterilization (tubal ligation), Vasectomy. 1- Combined hormonal contraception (COCP, Patches, Vaginal ring) 1- COCP: It contains a combination of two hormones: synthetic oestrogen and a progestogen. Oestrogens: Most preparations contain oestrogen ethinyl estradiol in daily dose Progestogens: (Second generation pills contain norethindrone and levonorgestrel, third generation pills include desogestrel, gestodene and norgestimate, pills containing newer progestogens, drospirenone and dienogest) Mechanism of action Centrally: inhibition of ovulation. both oestrogen and progestogen suppress release of FSH, LH which prevents follicular development within the ovary and therefore unovulation. Peripheral: making the endometrium atrophic and hostile to implantation and altering cervical mucus to prevent sperm ascending into the uterine cavity. Regimen Most brands contain 21 pills; one pill to be taken daily, followed by 7-day pill-free interval (the traditional 21/7 model). There are some evrey day preparations that include seven placebo pills that are taken instead of having a pill-free interval. Newer brands, , offer a wider combination of active pills and pill-free days with combinations such as 24/4, 84/7 and 365 (where a pill is taken daily without any breaks). Absolute contraindications Breastfeeding 15 cigarettes/day and age >35 Multiple risk factors for cardiovascular disease Hypertension: ≥160 / 100 mmHg Hypertension with vascular disease Current or history of DVT / pulmonary embolism Major surgery with prolonged immobilization Current or history of ischaemic heart disease, stroke Complicated valvular heart disease Migraine with aura, Migraine without aura and age >35 (continuation) Current breast cancer Diabetes for >20 years or with severe vascular disease, nephropathy, retinopathy or neuropathy Active viral hepatitis, severe cirrhosis Benign or malignant liver tumours Side effects (minor, major) ✔ Minor CNS: depression, headache, loss of libido. GIT: nausea and vomiting, bloated , weight gain, gallstones, cholestatic jaundice. Breast: mastalgia, breast enlargement. Reproductive: disturbance of menstrual cycle & increased vaginal discharge Others: chloasma, leg cramps, greasy skin, fluid retention ✔ Major Venous thromboembolism: third generation being twice to sustain VTE than second generation. Arterial disease is less common than VTE but more serious, risk of myocardial infarction, thrombotic stroke in young. cigarette smoking and high blood pressure will increase the risk. Breast cancer Positive health benefits light, pain-free, regular bleeds and therefore COC can be used to treat heavy or painful periods. It can also improve premenstrual syndrome (PMS) Reduce the risk of functional ovarian cysts, endometriosis, PID, ectopic pregnancy COC offers long-term protection against both ovarian and endometrial cancers. It can also be used as a treatment for acne Decrease iron deficiency anemia Decrease incidence of benign breast disease Enzyme inducer drugs Anticonvulsant (Carbamazepine, Eslicarbazepine, Oxcarbazepine, Phenobarbital, Phenytoin) Antibiotic (Rifampicin, Rifabutin) Antifungal (Griseofulvin) Protease inhibitors (Amprenavir, Atazanavir) Antiretroviral (Saquinavir, Ritonavir) Drug interaction This can occur with liver enzyme inducing agents such as some antiepileptic drugs, sulphonamide, rifampicin (reduce efficacy) Some antibiotics alter intestinal absorption of COC and reduce efficiency. Effectiveness of some drugs (aspirin, oral anticoagulants, oral hypoglycemics, lamotrigine) are decreased and that for some other drugs (beta blockers, corticosteroids, diazepam, aminophylline) are increased by COCP 2. Patches: releases norelgestromin 150 microgram and ethinylestradiol 20 microgram per 24 hours. Patches are applied weekly for 3 weeks, after which there is a patch-free week, same risks and benefits as COC, more expensive, may have better compliance 3. Vaginal ring: releases a daily dose of ethinyl estradiol 15 μg and etonorgestrel 120 μg.The ring is worn for 21 days and removed for 7 days, during which time withdrawal bleed occurs, same risks and benefits as COC, more expensive If she forget pills, what should she do? 2- Progestogen only contraception 1. Progestogen only pill (or mini-pill) Injectable is the only hormonal method that may delay 2. Sub dermal implant (Implanon) return of fertility after discontinuation, it may take up to 1 3. Injectable (Depo-Provera, Noristerat) year after last injection for ovulation to return 4. Hormone-releasing intrauterine system (Mirena) Mechanism of action They have local effect on cervical mucus (making it hostile to ascending sperm) and on the endometrium (making it thin and atrophic), thereby preventing implantation and sperm transport. The higher dose progestogen only methods will also act centrally and inhibit ovulation, making them highly effective. Side effects Erratic or absent menstrual bleeding Simple, functional ovarian cysts Breast tenderness Acne. It is taken every day without a break and If the POP fails, there is a slightly higher risk of ectopic pregnancy. Indication Breastfeeding Old age Cardiovascular risk factors e.g high blood pressure, smoking or diabetes. 1- Injectable progestogens — Depot medroxy progesterone acetate (DepoProvera/DMPA);each injection lasts for 12 weeks with a 2-week grace period thereafter. — Norethisterone enanthate (Noristerat): lasts for 8 weeks and is not widely used. ✔ Benefit Most women who use it develop very light or absent menstruation. It will improve PMS and can be used to treat menstrual problems such as painful or heavy periods It is very useful for women who have difficulty remembering to take a pill regularly. ✔ Risk It causes low oestrogen level (associated with loss of bone mineral density), Women with pre-existing risk factor for osteoporosis should be advised not to use Depo-Provera in long term. ✔ Side effects Weight gain of around 2–3 kg in the first year of use Delay in return of fertility (may take around six months or longer to conceive compared to a woman who stops COC) Persistently irregular periods; most women become amenorrhoeic 2- Implanon Inserted subdermally under local anesthetic into the upper arm It is the progestogen etonogestrel which is metabolized to the third-generation desogestrel It lasts for three years and thereafter can be easily removed and a further implant inserted if requested. ✔ Benefit: Useful for those who have difficulty remembering to take pill, who want long-term contraception. ✔ Risk: rapid return of fertility when it is removed, irregular bleeding (major reason for early discontinuation) 3- Hormone releasing intrauterine system (Mirena) Mirena has a capsule containing levonorgestrel around its stem which releases a daily dose of 20 μg of hormone. It is associated with dramatic reduction in menstrual blood loss and is licensed for contraception, the treatment of heavy menstrual bleeding and as part of a hormone replacement therapy (HRT) regimen. ✔ Contraindication Current STI or PID, including post-abortion and following childbirth Malignant trophoblastic disease Undiagnosed vaginal bleeding (before assessment) Endometrial and cervical cancer (until assessed and treated) Known malformation of the uterus or distortion of the cavity e.g fibroids Copper allergy (could use mirena) ✔ Special considerations Increase risk of pelvic infection in the first few weeks after insertion (no long-term risk) No risk of PID, and not protect against STD Users have lower risk of pelvic infection bcs of protective effect of hormone on the upper genital tract. Antibiotics are not given routinely during insertion but should be considered if woman is thought to be at higher risk or if there are limited facilities for STI screening IUD prevents all types of pregnancy, including ectopic pregnancy. However if a pregnancy ✔ Complications occur, risk of it being ectopic is around 3–5 per cent ( 80 ml, prolonged > 7 days or both. Intermenstrual bleeding: scant bleeding at ovulation for 1 or 2 days. *PALM-COEIN FIGO Classification Causes of AUB: ✔ Organic condition 1- Genital tract Problem (Local Causes) regular (cyclic): causes {Fibroid, Endometriosis, Adenomyosis, PID} irregular (acyclic): causes {polyps, cancer} 2- Trauma & Psychological causes 3- Systemic disorders & blood Dyscrasias , Hepatic & Thyroid & Hypertension 4- Pregnancy status as RPOC , ectopic pregnancy & H. Mole 5- Iatrogenic as Exogenous estrogen (eg. oral contraceptive) ,progestins contraception, injectable steroid , Aspirin, Heparin, Warfarine , Tamoxifen, Intrauterine device. ✔ Dysfunctional uterine bleeding (non- organic) If the bleeding is not due to the above causes. Risk factors of DUB: Age (more common in teens and perimenopausal women), weight, smoking, PCOS Causes of DUB 1- Anovulatory (commonest one about 85%): No corpus luteum so no progesterone → ↑estradiol which cause endometrial overgrowth and thickening, then necrosis and irregular bleeding. (In adolescence and perimenopausal) 2- Ovulatory (Presents as menorrhagia): defect in local endometrial hemostasis, prostaglandin imbalance and alterations in fibrinolysis. More prostaglandin E2 and less prostaglandin, PGF2α lead to increased fibrinolytic activity Prostaglandin F2α cause (vasoconstriction+ muscle contraction) prostaglandin E2 cause (vasodilatation+ contraction) PGI2 causes (vasodilatation+ relaxation) 3- Cystic glandular hyperplasia = Simple endometrial hyperplasia: estrogen production raises to high level but there is no inhibition of pituitary gland, so FSH secretion and high E level continue, There is amenorrhea during this time but prolongation of action of estrogen In the absence of progesterone lead to endometrial hyperplasia. Bleeding is heavy, prolong, irregular, happen due to decrease in E, and growth of endometrial blood supply. Luteal phase is fixed =14 days -No. of Pads/day Follicular phase is changing -Amount of blood in each pad e. g if cycle is 28 days ovulation occur at day 14 -Presence of clot -if cycle is 32 days ovulation occur at day 18 -Interfere with daily activity or not -if cycle is 22 days ovulation occur at day 8 Approach History (>7 days, period less than every 21 days, heavy, irregular, history of amenorrhea for 1 to 2 months then develop heavy ,prolong and irregular bleeding, history of PCOS, and smoking) Examination (general, pelvic, abdominal) Investigations Laboratory evaluation (CBC, iron, coagulation screen, β-hCG, high vaginal and endocervical swabs if there is discharge and high risk of PID, prolactine level, thyroid function test, liver function test) Diagnostic procedure (Pelvic US, cervical cytology (pap smear + HVS), endometrial biopsy using pipelle which is flexible syringe suction curette, hysteroscopy and (D&C) Treatment: according to the cause of bleeding 1- Massive intractable bleeding: admission to hospital, IV conjucated estrogens, after bleeding stop use estrogen orally daily for 25 days and add medroxyprogestron acetate for the last 10 days of treatment allow 5-7 days for withdrawal bleeding, Or administer mirena which release levonorgestrel through IUD. 2- Moderate Menometrorrhagia : Estrogen-progestron combination: (conjugated estrogen orally each day for 25 days with medroxyprogestrone orally for last 10 days of the estrogen treatment, or oral contraceptive for 21 days with a 7 days withdrawal) Cyclic progestin: (medroxyprogestron orally each day for 10-15 days each month usually for 3 months trial, or mirena with levonorgestrel-releasing IUD. 3- For older patient who do not response to medical therapy and who donot anticipate later pregnancy endometrial ablasion hystrectomy Uterine ablasion Hysterectomy Types Types 1.Balloon thermal ablation 1.Supracervical Hysterectomy (also called “Subtotal 2.Cryoablation or freezing Hysterectomy” or “Partial Hysterectomy 3.Electrosurgery 2.Total Hysterectomy (“Traditional Hysterectomy”) 4.Hydrothermal ablation 3.Radical Hysterectomy 5.Microwave 6.Radiofrequency Complication 1.Bleeding Complication 2.Damage to nearby organs 1- Fluid over load 3.Infection either of wound or urinary tract 2- Uterine perforation 4.Wound dehiscence 3- Thermal damage to adjusent organ 5.Incisional hernia 6.Vault prolaps Contraindications 1-Desires future fertility 2-endometrial cancer/hyperplasia 3-active genital or UTI 4-anatomical or pathological endometrial weakness Prognosis Response to treatment for DUB is highly individualised, outcome depends on medical condition and age. Many women, especially adolescents, are successfully treated with hormones (usually oral contraceptives). Hysterectomy removes the source of problem but this operation has many complications. Prevention Dysfunctional uterine bleeding is not preventable disorder Management General Rest is advised during bleeding phase, anemia should be corrected by diet, drugs, or blood transfusion. Medical: Respond well to conservative treatment during adolescence and early reproductive period. - Nonhormonal Prostaglandin synthetase inhibitors: NSAIDs as mefenamic acid (second line of medical treatment) Antifibrinolytic agents (tranexamic acid) as a second line therapy - Hormone Progestins: The common preparations used are norethisterone acetate and medroxyprogesterone acetate  Endometriosis & Adenomyosis Endometriosis: Endometrial tissue outside endometrial cavity, it is benign (not cancerous). More common in tall, thin, low BMI, white women, women who delay their pregnancy or is infertile. Mostly occur during reproductive years (25-35) and regress with menopause or pregnancy. Cause Unknown, but there are some theories and possibilities: Backup of menstrual flow to fallopian tube, abdominal cavity during menstruation (retrograde menstruation). Genetic and immune components Surgical transfer (seen in surgical scars e.g episiotomy or C/S scar) Hematogenous, lymphatic (for rare cases that develop in lung, brain and distant from the pelvis) Coelomic metaplasia Ovary, uterus, fallopian tube Anterior and posterior cul-de-sac Posterior broad ligament, uterosacral ligament, Round ligament Sigmoid colon, appendix Location, clinical features Major symptom of endometriosis is severe recurring pelvic pain Ovary (endometrioma = chocolate cysts, can become complicated) Fallopian tube (adhesions, ectopic, infertility) Uterine ligaments (chronic pelvic pain, low back pain, dyspareunia, cervical motion tenderness). Peritoneum, Bowel wall (abdominal pain & adhesions, GIT symptoms). Bladder wall (dysuria…) Pouch of Douglas = posterior cul de sac (dyschezia) Uterus (Adenomyosis) Distant: lung, vertebra, skin (episiotomy, C/S scar site). Symptoms are cyclical (around time of menses, maybe associated with heavy, prolonged or frequent menses) Infertility is either tubal factor or due to toxic factors released by lesions. or is a cause of endometriosis in the first place. Site of pain related to site of endometriosis Dysmenorrhea, (progressive pain), lower back pain linked to the pelvis Chronic pelvic pain (lower back pain, or abdominal pain) Dyspareunia, dysuria, urgency, frequency, and dyschezia (painful defecation) Nausea, vomiting, and/or diarrhea just prior or during the period Frequent menses flow or short menstrual cycle Heavy and/or long menstrual periods. Some women may also suffer mood swings and fatigue. Women who are diagnosed with endometriosis may have gastrointestinal symptoms that may mimic IBS Abdominal examination: could be normal, mass in the lower abdomen (enlarged chocolate cyst or Diagnosis tubo-ovarian mass due to endometriotic adhesions) History Pelvic examination: could be normal, expected findings are (pelvic tenderness, nodules in pouch of Douglas, nodular feel of uterosacral ligaments, fixed retroverted uterus, adnexal mass) Examination Speculum examination may reveal bluish spots in the posterior fornix. Investigation Rectal or rectovaginal examination is often helpful to confirm the findings. CBC CA 125 could be elevated but not specific, helpful to assess therapeutic response, follow-up, and recurrence. TVUS (chocolate cyst ), MRI (cysts & adhesions) Laparoscope diagnostic (with biopsy) & therapeutic (removal) Definitive diagnosis = laparoscope + biopsy (Endometriosis) Definitive diagnosis = Hysterectomy + biopsy (Adenomyosis) Treatment No cure with any modality Aim to relieve pain, prevent progression, relieve infertility (may need fertility drugs or IVF). Medical (suppress pain & cycle): Analgesics (NSAIDs, narcotics) Progestins, COCP (counteracts estrogen and inhibits the growth of the endometrium) Androgens (danazol, gestrinone) → inhibit growth of endometriosis, it’s use limited bcs may cause hirsutism Aromatase inhibitor (block formation of estrogen) GnRH agonist (lupron depot): Consistent stimulation of GnRH receptors results in down regulation, inducing profound hypoestrogenism by decreasing FSH, LH level. they induce unpleasant menopausal symptoms, and may lead to osteoporosis Surgical Laparoscopy (conservative, ablation or removal of endometrial tissue, maintain anatomy) if she doesn’t completed her family Laparotomy (Radical hysterectomy → reserved for women with chronic pelvic pain and treatment resistant) Presacral neurectomy (more effective if pain is midline, with risk of chronic constipation due to injury to the parasympathetic nerve) Follow up by US If asymptomatic → expectant management If desires pregnancies → analgesics only If desires future pregnancy → any method except radical surgery which is used in resistant cases who are old or completed family Complications of endometriosis Endocrinopathy (this may be responsible for infertility) Rupture, Infection of chocolate cyst Obstructive features: Intestinal obstruction, Ureteral obstruction → hydroureter → hydronephrosis → acute pyeloniphiritis Malignancy risk of ovarian cancer in women with endometriosis four fold Adenomyosis: Presence of endometrium within the myometrium. focal or diffuse (enlarged globular uterus) Associated lesions: leiomyoma, fibroid, endometriosis, endometrial polyp, hyperplasia & cancer. More in old (40-50 years), multiparous, pregnancy (diagnosed by MRI). no relation to time of first pregnancy or C/S. Symptoms Asymptomatic in 35% of cases Menorrhagia (related to dysfunctional contraction, PG changes, anovulation & associated lesions) Dysmenorrhea/pelvic pain (related to extent), metrorrhagia, dyspareunia. Treatment Medical NSAIDs (Mefenamic acid) & Tranexamic acids. Continuous low dose COCP with withdrawal bleeds every 4-6 months. GnRH ⊕, Danazol (especially loaded to IUD), Mirena for menorrhagia, Mifepristone. Surgical Laparoscopic myometrial electrocoagulation Endomyometrial ablation or resection (if no desire for pregnancy) Conservative surgery Uterine artery embolisation Hysterectomy (for women more than 40 years of age who have completed their families) Definitive surgery  Fibroid Fibroid “myomas or leiomyomas”: is a benign tumor of uterine smooth muscles, made up of round whorls of smooth muscles and connective tissue, hormone dependent (estrogen & progesterone). ↑ risk: reproductive age (30s, 40s), black, nullipara, FHx , obesity, smoking. ↓ risk: menopause, weight loss, healthy diet, long term OCPs & depoprovera. Types Intramural (commonest) Subserosal (can be large or pedunculated) Submucosal (can be pedunculated & hang through cervix) Cervical (damages surrounding when removed) Interligamentous (difficult to remove) Parasitic (attach to another organ) Symptoms depends on size: Asymptomatic in 50% Menstrual disturbance (menorrhagia, IMB, PCB might lead to IDA, dysmenorrhea) Dyspareunia Bladder symptoms as frequency, dysuria, urgency, retention Bowel symptoms (from pressure “retention, constipation & haemorrhoids”) Effects in pregnancy: Pre-conception: mostly harmless, but some can block the entrance to fallopian tubes (infertility & ectopic), or submucosal can lead to recurrent miscarriages. Pregnancy: fibroids grow during pregnancy because of higher levels of oestrogen. another effect of pregnancy on fibroids called 'red degeneration.' This is when a center of fibroid cut off from blood supply so it under go necrosis → pain, contractions ± PPROM & PTL → Treated conservatively by analgesic, fluids & tocolytics, can cause IUGR and malpresentation also. Labor: can block the passage and need C/S Post partum: PPH, puerperal pyrexia and infection Possible changes or complications Necrosis Torsion from twisting if pedunculated Hyaline degenration (in menopause) Calcification. Malignant transformation (sarcoma) in about 0.1 % Infection Diagnosis History Examination (general, abdominal, pelvic and bimanual) Investigation (US, hysteroscopy, laparoscopy) US (gold standard), if not clear → hysteroscopy or laparoscopy for diagnosis and you can take biopsy also Differential diagnosis Any abdominal & pelvic mass in reproductive years Pregnant uterus Ovarian tumor Sarcoma of uterus Treatment Depend on severity, symptoms, position, size, age, fertility, If near menopause → wait to regress spontaneously. Medical (not for cure, only symptomatic relief) conservative treatment if (small, near menopause, in pregnancy), But you should follow up by ultrasound Treat IDA by oral iron Tranexamic acid better than NSAIDs for menorrhagea COCP (50%↓menorrhagea) Depoprovera (long term use protect from fibroid) Mirena better than copper IUD Danazol & gesteronon (reduce size & blood loss from fibroid) Mifepristone (it is antiprogesteron, decrease size of fibroids & less effect on bone density) GnRH ⊕ [↓oestrogen levels so cause shrinkage. when taken for six months, can reduce the size of fibroids by up to 50%, also stop menstrual bleeding and pelvic pain], (last option of medical therapy, also used prior to myomectomy or hysterectomy to ↓ bleeding) GnRH agonist need back up with tibolone, or low dose estrogen, or conjugated estrogen with cyclical norethesteron or continuous norethesteron for 2 years) Surgical (for cure) Curable choice (surgery, menopause in all case except in malignancy bcs fibroid carry risk of malignancy) MRI guided laser Myomectomy (laparoscopy, hyteroscopy if submucosal 65 years: No screening provided normal testing over past 10 years. No high grade dysplasia (CIN 2/3) in past 20 years. Exceptions: Women with HIV seropositivity, immunosuppression, exposure to DES in utero: these need annual screening. Women following total hysterectomy for benign conditions: No follow up, in subtotal hysterectomy need screening Sensitivity ~50%, Specificity ~ 92% with 10-15 % chance of false positive or false negative results. Screening for CIN reduces mortality from cancer cervix. Those with positive screening test should be referred to colposcopy for diagnosis and treatment. Procedure is done in lithotomy position with cusco speculum in place: Wooden (Eyre’s) spatula: Exfoliated cells are collected by scraping the cervix. Use concave, Rotate 360 degrees, Not too much force (bleeding, pain), Not too little force (inadequate sample) Spread on glass slides, As thin as possible, Properly labeled, Fixation of samples immediately with alcohol. Cytobrush: Insert ~ 2 cm (until brush is fully inside cervical canal) Rotate only 180 degrees (otherwise will cause bleeding) Broom Insert to external os Rotate 5 times in a clockwise direction Colposcopy Colposcopy is a binocular operating microscope with low magnification power (between 4 & 25 times). It has been used to examine the cervix in detail to identify CIN and preclinical invasive cancer It is only considered satisfactory if healthy columnar epithelium is identified. done in lithotomy position with cusco speculum. Colposcopy gives a clinical diagnosis. Punch biopsy from the abnormal area gives a histopathological diagnosis (colposcopic- directed biopsy). 3 steps of colposcopy 1. Inspection of cervix and its vasculature: Green filter may help studying vasculature which highlights the blood vessels as black lines. Abnormal vasculature (punctuation and mosaicism) which are feature of CIN. Abnormal branching vessel (Bezarre shape vessels) suggestive of micro-invasive carcinoma. 2. Acetic acid test: application of 3% acetic acid: Stains normal area pinkish. Stains abnormal area white (large amount of protein). degree of staining correlates with severity of lesion. 3. Schiller test: application of Lugol’s iodine: Stains the normal cervix brown (abundant collagen). Stains abnormal area are yellow Prevention of HPV Infection HPV vaccine Behavioural interventions Adenocarcinoma in situ Delaying sex until cervical epithelium in TZ mature Less common than squamous intraepithelial neoplsia Limiting number of sexual partners, and number of children Has same risk factors Condom use Can not be reliably screened by colposcopy Does not have particular colposcopic features Other measures Divided into high grade and low grade Maintain local hygiene and to treat vaginal infections. Characterized by skip lesions Maintain penile hygiene (reservoir for high risk HPV) Treatment by large cone biopsy Stop smoking reduces CIN. Nabothian follicle: endocervical glands in transformational zone become covered with squamous cells and forms mucus filled retention cysts. Endocervical polyp: common and increases with age up to the menopause, producing heavy vaginal discharge or bleeding upon coital contact. Histology :columnar epithelium sometimes with metaplastic squamous epithelium across the tip Malignant change is most unusual, treated by: polypectomy, send for histology. Cervical ectropion (erosion) Physiological presence of columnar epithelium on the ectocervix. Increases in pregnancy and OCP. May lead to vaginal discharge and PCB. Management: reassurance, exclude other cause, if distressing symptoms do coagulation. Cervical cancer 4-6 % of female genital cancers. Age: 40-50 years old Risk factors and aetiology Coitus at young age, multiple partner Smoking Immunosuppression (renal transplant, HIV) HPV (Human papilloma virus ) infection mainly 16,18 Previous CIN Poor uptake of screening program Long term use of the contraceptive pill (more unprotected sex) Low socioeconomic class Male related factors − Number of the partners in previous sexual relationships is relevant − Cervical cancer risk increased if partners has penile cancer − Previous wife with cervical cancer. Types Growth type; Exophytic: is like cauliflower filling up the vaginal vualt. Endophytic: it appears as hard mass with a good deal of induration. Ulcerative: an ulcer in the cervix. Pathological types: Squamous cell carcinoma 70- 90% Adenocarcinoma 10-30% Clinical features Early symptoms [[Thin, watery, blood tinged vaginal discharge, Blood stained foul vaginal discharge, Abnormal vaginal bleeding as (IMB, PCB, Perimenopausal, Postmenopausal)]] Late symptoms [Pain due to spinal cord infiltration, leg oedema, urinary symptoms (dysuria, hematuria, incontinence due to fistula), rectal symptoms (bleeding, constipation, hemorrhoid), uraemia due to ureteric obstruction] Diagnosis History Many are asymptomatic presented with abnormal pap smear or after LLETZ or with variety of symptoms according to stage of disease Examination Mainly vaginal examination using Cusco's speculum (nothing is found in early stage) Mass, ulcerating fungating in the cervix P/V and P/R is very helpful and may be done under anesthesia. Pap /colposcopy / and biopsy may be done as outpatient and is crucial to confirm malignancy and type of it Staging Best to follow FIGO system. staging may require the following: EUA (Bimanual palpation, P/V, P/R). MRI, Cystoscopy, Proctoscopy EUA= Examination under anesthesia Treatment Surgical Radiotherapy (teletherapy, brachytherapy) Radiotherapy & Surgery Radiotherapy and Chemotherapy followed by Surgery Palliative treatment Microinvasive squamous tumour (stage Ia): carry good prognosis, conservative (LLETZ or knife cone biopsy) or simple hysterectomy Squamous tumour (stage Ib1): may be suitable for fertility sparing surgery (radical trachelectomy) which involves removal of 80% of cervix & parametrial tissues with resection of pelvic lymph nodes or simple hysterectomy if complete her family. Early invasive squamous cell disease (stage Ib2, IIa): Wertheime’s hysterectomy or radiotherapy (equal success rates) 5 years survival rate: Advanced stage (IIb, III, IV): radiotherapy ± chemotherapy. Stage I -- 80% Stage II -- 50-60% Adenocarcinomas: radical surgery. Stage III -- 30-40% Stage IV -- 4% For recurrent disease : Local recurrence: use of radiation if it is not used previously, or pelvic exenturation if she already received radiotherapy. Distant disease: chemotherapy Palliative therapy For stage IV Radiotherapy ( usually intracavitary selenium), extensive surgery, chemotherapy. Good nursing care, analgesic (Codein sulfate, Pethidine, Morphine, Diamorphine), antiemetic IV drip, entral, and parentral feeding, Urinary Catheterization. Treatment depend on age, stage (by Dr shang) simplified Fertility preservation (til 2A there is chance, after that no chance) [Cone biopsy, Large loop excision, Radical trachelectomy] Completed family: (hysterectomy) Stage I (Knife cone biopsy, Simple hysterectomy, Radical trachelectomy) Stage II, III, IV (Chemo-radiotherapy)  Endometrial cancer Most common female reproductive cancer (6% of all cancers in women) Generally high rate (70%) of survival due to early presentation (abnormal bleeding) and early diagnosis Histologic types of endometrial cancer Type I: estrogen dependent, comprising about 80%: Mostly adenocarcinoma Type II: Non-estrogen dependent, more aggressive → worse prognosis – Papillary Serous – Clear cell – Adenosquamous – Undifferentiated Other uterine cancer: Leiomyosarcoma (Rapidly growing fibroid) Stromal sarcoma Carcinosarcoma (MMMT) = malignant mixed mullerian tumor. The exact cause is unknown but hypothesis exists: Type I: exposure to unopposed estrogen. Type II: associated with endometrial atrophy in postmenopausal women and strong genetic predisposition. How endometrial hyperplasia is associated with endometrial cancer Endometrial hyperplasia is a continuum: Simple hyperplasia → complex hyperplasia without atypia → complex hyperplasia with atypia→ endometrial cancer. Endometrial Hyperplasia: Simple – Benign irregular dilated glands. – Often regress spontaneously, with atypia: 8% progress to cancer – Progestin treatment used for bleeding may help in treating hyperplasia as well Complex – Proliferation of glands with irregular outlines, back to back crowding of glands. – wirh atypia: 29% progress to cancer – Complex hyperplasia with atypia treated by hysterectomy or progestin (depends if she finished family or not) Risk factor Early menarche (age 52) Infertility or nulliparous Obesity (conversion of andogen to estrogen by adipose tissue), diet high in animal fat Tamoxifen use for breast cancer HRT after menopause Diabetes (higher estrogen) Age greater than 40 Caucasian women Family history of endometrial cancer or HNPCC (hereditary non polyposis colon cancer ) Personal history of breast or ovarian cancer Prior radiation therapy for pelvic cancer Reduce risk: COCPs → 50% reduced rate Tobacco smoking (lower levels of estrogen and lower rate of obesity) Physical activity Multiparty Symptoms of endometrial cancer Non-menstrual bleeding or discharge (especially post-menopausal bleeding) Heavy bleeding & discharge Dysuria, dyspareunia Pain and/or mass in pelvic area Weight loss Back pain Enlarged uterus which may associated with pyometra Diagnosis of endometrial cancer History on US, endometrial thickness > 16 mm in premenopausal & > 4 in postmenopausal. Pelvic Examination Pap smear (detect cancer spread to cervix) TVUS (thickness should be < 4mm in post menopausal women) Endometrial biopsy by pipelle (91 - 99%) as initial test, indicated if ET is >4mm Hysteroscopy with endometrial sampling (gold standard) if pipelle is inconclusive or high suspicion (hyperplasia with atypia, pyometria, presence of necrosis, or persistant bleeding) Alternatively D&C and send sample for biopsy Speculum examination: cervix looking healthy and blood or purulent offensive discharge escapes out of the external os. For suspected advanced stage: - Cystoscopy Bimanual examination: uterus is normal, atrophic, or enlarged due to spread of the - Sigmoidoscopy tumor, uterus is usually mobile unless in late stage, when it becomes fixed. - Pelvic and Abdominal CT Rectal examination Regional lymph nodes and breasts are examined carefully. - CXR - MRI (will give useful information regarding the extent of disease) - Labs: CBC, LFT, RFT. Spread Direct extension (most common) Transtubal Lymphatic (Pelvic usually first, then para-aortic) Hematogenous (Lung most common, liver, brain, bone) Pathological terminology in endometrial cancer Stages ▶Type Stage I: Confined to uterine body: Type 1 Type 2 - IA: limited to endometrium - IB: invades < ½ of myometrium ▶ Grade (I, II, III) - IC: invades > ½ of myometrium Histological analysis differentiate between low grade and high grade, higher grade is more aggressive. Stage II: Cervix involved: - IIA: Endocervical gland involves ▶ Stage - IIB: Cervical stromal invasion FIGO staging describes the size and spread of the tumour and is used with the above to give Stage III: local and/or regional spread: prognostic information to patients. - IIIA: invades serosa/adnexa, or positive cytology - IIIB: vaginal metastasis - IIIC: metastasis to pelvic or para-aortic lymph nodes Stage IV: - IVA: invades bladder/bowel mucosa - IVB: distant metastasis Treatment of endometrial cancer Surgery (all of below) - Total Hysterectomy - Bilateral Salpingo-oophorectomy (BSO) - Pelvic lymph node dissection (PLND) - Laparoscopic lymph node sampling Radiotherapy Chemotherapy Hormone therapy (Progesterone, tamoxifen) Stage IA, IB: Surgery IC, II: Surgery, adjuvant chemotherapy III: Surgery, adjuvant chemotherapy IV: Palliative radiotherapy and chemotherapy Prevention of endometrial cancer Early detection is best prevention Treating precancerous hyperplasia (10 ~ 30% untreated develop into cancer) – Hormones (progestin) – D&C – Hysterectomy  Vulva & Vaginal disorder Classification of vulvar disease Non neoplastic Lichen sclerosis VIN Squamous cell hyperplasia Contact and allergic dermatitis, Seborrhoeic dermatitis, Lichen planus, Psoriasis, other dematoses Neoplastic Benign cyst (bartholin’s, skene’s, and inclusion cysts) Wart Fibroma, lipoma Malignant: Vulvar cancer Lichen sclerosis Is a destructive inflammatory skin condition (believed to be autoimmune) which affects mainly anogenital area. another theory is that androgen in diseased area is decrease and application of androgen in this area will improve condition. Associated with vulval cancer 3-5% risk (not cause), and other autoimmune conditions may present. Inflammation in to subdermal layers of skin → hyalinization, fragility, white parchment paper appearance of skin → presents mainly with itching and soreness (due to scratching), superficial dyspareunia. On examination: whitening, fissuring, and loss of anatomy. Treatment No cure, the goal is to ↓ symptoms, ↓ progression and early detection of cancer → multidisciplinary approach (education, behavior modification, psychological support, and pharmacologic) Good skin care (hygiene) and minimizing both chemical and pressure irritation. Potent steroids are first line either topical or intralesional. Surgery should be reserved for cases of malignancy or significant post inflammatory sequelae. Vulvodynia Chronic vulvar pain, discomfort without identifiable causes, result from hypersensitivity of nerve endings in skin of vulva Symptoms include feeling of burning or irritation, pain over entire vulva or only in one place, such as clitoris (clitorodynia) or vestibule (vestibulodynia). Causes of vulval pain Infection (bacterial, viral) Tissue and nerve damage (surgery) Pressure due to tampon insertion, gynecologic examination and prolonged sitting Neurologic disorders (neuropathy) Allergy to soap and hygiene products Hormonal changes Genetics, Immunology Diet Diagnosis Features, normal physical findings, and absence of identifiable causes per the differential diagnosis. Cotton swab testing is used to differentiate between generalized and localized pain, may or may not include a biopsy of any areas of skin appear suspicious Differential diagnosis Infection, after traumatic labor, pelvic surgery, IBD, psychological cause, sexual abuse, birth trauma Treatment of vulvodynia: Lifestyle change (wearing cotton underwear) Biofeedback training , physical and relaxation therapy Medications like creams or ointment containing lidocaine, estrogen or tricyclic antidepressants. Surgery (if conservative treatment is not effective) by vestibulectomy, during which nerve fibers to area are cut out Vulval intraepithelial neoplasia (VIN) Pre-malignant skin condition either by HPV or lichen sclesosis, often in postmenopauasal women Symptoms: pruritus, pain/burning sensation, vulvar soreness, bleeding/discharge, persistent ulcer, color changes, urinary symptoms, lump or wart like growth. Examination: different findings like indurated, pigmented lesions, or eroded areas on the labia. No screening for VIN so we use colposcopy which can discover it accidentally if asymptomatic. histologic diagnosis from biopsy of most abnormal-appearing area is necessary before giving treatment. Treatment VIN 1 may be reassessed annually and generally resolve spontaneously Others treated by excisional surgery, ablative surgery by laser, Immunomodulating cream (e.g. imiquimod) Vulval cancer Common in elderly, mean age is 65, present similar to VIN but should also examine anal, vaginal & cervix areas. Types: SCC 90% Melanoma 5% BCC 1-2% Sarcoma 1-2% Adenocarcinoma (rare) Investigation Biopsy Imaging (CXR, CT, MRI) Stage: as in picture Poor prognostic factor: if large size > 4 cm, sphincter involved, groin node metastasis. Treatment Stage 1, 2 (radical vulvectomy) If there are LN involvement > unilateral or bilateral inguinofemoral lymphadenectomy + radiotherapy Stage 3, 4 (add inguinofemoral lymphadenectomy, RTx + CTx) Atrophic vaginitis is the most common cause of bleeding after postmenopause Benign cyst of vulva Bartholin cyst: blockage of long duct, fluid collection (cyst), if infected, become bartholin abscess. Causes: episiotomy, congenital stenotic duct, desquamated skin, duct infection (gonorrhea/chlamydia because it is columnar epithelium) Mostly small & asymptomatic. Larger or infected one present with severe pain, unilateral round-ovoid, tense red & tender mass located at lower vestibule (5 or 7 o’clock). Treatment: marsupialization (drained but not sutured totally) Epidermal inclusion cyst: collection of desquamated epithelial cells encapsulated by stratified squamous epithelium in the dermis of the vagina. variable in size and are visible through the vaginal mucosa as round white masses that is filled with viscous, gritty, or caseous foul-smelling contents that closely resemble a purulent exudate. Asymptomatic, no further evaluation is required except in case of infection (drainage is recommended) Vaginal intraepithelial neoplasia (VAIN) Similar risk factor to CIN, can progress to SCC. Rarely found as primary lesion, most often develops as extension of CIN in upper third (vaginal vault) or suture lines after hysterectomy. Cervical or vulvar neoplasia increases risk for VaIN and vaginal squamous cancer. Generally asymptomatic, if present symptoms may include vaginal bleeding, discharge, and odour, abnormal cytology is most often the first indication of VaIN, particularly if the patient lacks cervix Colposcopic examination to locate the vaginal lesion for biopsy Treatment (depend on grade which determined by colposcopic and histologic findings) VaIN 1: Observation VaIN 2 & 3: Excision either wide local excision or partial vaginectomy, Medical ablation (5% fluorouracil cream), CO2 Laser ablation (if multifocal), radiotherapy (many side effects) Vaginal cancer Rare, unknown cause, late detection, poor prognosis. Commonest type is SCC, usually in upper third, similar risk factors to cervical cancer Presents with bleeding, pain, discharge. Diagnosis History Examination under anesthesia Investigation: biopsy, may need sigmoidoscopy, cystoscopy, CXR, urogram, CT, MRI, D&C, endometrial biopsy. Stages: Stage 1 confined to mucosa Stage 2 subvaginal infiltration Stage 3 Extends to pelvic wall Stage 4 extends to rectum, bladder or beyond. Treatment Stage 1, 2 surgery or radiotherapy Stage 3, 4 radiotherapy, chemotherapy Follow up every 3 months for 2 years then every 6 months for 5 years. Recurrence: confirmed by biopsy and treated by chemotherapy. Complications: vaginal stenosis,adhesions, ulceration, necrosis, fistula. Uncommon vaginal tumors Rhabdomyosarcoma (sarcoma botryroides): most common soft-tissue tumor in genito-urinary tract during childhood (90% of cases occur in age 4-5 attacks/year: test for HBV, HIV & DM. treated by oral fluconazole (induction regimen 3 doses every 72 h for acute episode followed by a maintenance regimen once/weekly for 6 months to prevent further recurrences. 2- Trichomoniasis (protozoa) Infect vagina and urethra of both sexs. women are more likely to have symptoms than men. - Intense itching, Dyspareunia, Dysuria. - Hemorrhagic spots on cervix (strawberry cervix). - Greenish-yellow frothy (bubbles) discharge of bad odour. Diagnosis: Take high vaginal swab for wet mount preparation and Gram stain & culture, gold standard is a nucleic acid amplification test (NAAT) preferably on a vaginal, endocervical swab or on urine. Treatment - Metronidazole 500 mg twice daily for 5-7 days or 2 g as a single dose. - Tinidazole 2 g single dose - Treat the partner & abstain from intercourse during treatment for any STI 3- Bacterial Vaginosis caused by imbalance in “good” and “harmful” bacteria that are normally found in vagina → ↑ gardenilla vaginalis (gram variable cocobacilli), genital mycoplasm, anaerobs and ↓lactobacilli, It is not a true vaginitis (no inflammation of vaginal wall) Features Homogenous thin greyish-white discharge that has a strong fishy smell that is exacerbated (around the time of menses, in those who have IUD, and with intercourse bcz semen is alkaline) Typical presentation is bad odour discharge during intercourse Diagnosis Very important to treat BV in pregnancy as it increase PH > 4.5 risk of T2 miscarriage and PROM →PTL Whiff test by adding 10% KOH → fishy ouder High vaginal smear → ↑ Gramvariable cocobacili and ↓ lactobacilli Microscopy which will show clue cells Treatment Metronidazole (500 mg twice daily for 5-7 days or 2gm as a single dose oral or cream, clindamycin cream. although is not STD so no need to treat partner Upper genital tract infection Chlamydia trachomatis obligatory intracellular bacterium. May be asymptomatic or: - Cervicitis → mucopurulant vaginal discharge, lower abdominal pain, red, swollen and edematous cervix → PCB (post coital bleeding), IMB (inter-menstrual bleeding) - Dysuria (sterile pyuria: ⊕ WBC, ⊖ culture) - Can lead to PID with it's consequences. - Can cause Reiter’s syndrome: urethritis, reactive arthritis, conjunctivitis (can't see, can't pee, can't climb a tree) - If women is pregnant → risk of opthalmia neonatorum & pneumonia. Diagnosis: Sample for chlamydia/gonorrhea is from the endocervical discharge and first stream urine (not high vaginal, not MSU) - Nucleic acid amplification test NAAT( gold standard) on urine or vaginal discharge - LCR (ligase chain reaction) - PCR on first urine sample - Swab of urine and cervical discharge for culture, but (expensive, not widely available), it is 100% specific. - ELISA (limited use) Screening of CT Partners (if women diagnosed or suspected) History of chlamydia in the last year Patients ≥ 2 partners within 1 year Woman undergoing termination of pregnancy History of other STD & HIV Treatment : General advice for chlamydia & gonorrhea - Avoid intercourse until both treated - Use barrier contraception - Retesting if any doubt about complete treatment, test of cure should be performed minimum of 5 weeks after initiation of treatment - Contact tracing if multiple partners - Follow up with in 2-4 wks - If change partner, retesting between 3-12 months is recommended - Antibiotics for uncomplicated chlamydia; Doxycycline, Azithromycin, erythromycin. (Ceftriaxone for gonorrhea) Neisseria Gonorrhoea Gram ⊖ diplococci. Chronic asymptomatic infection is common (50% of women, 70% of men) - Cervicitis: discharge, contact bleeding, lower abdominal pain, cervical motion tenderness. - Urethritis: dysuria/urethral discharge - Proctitis: rectal bleeding, discharge and pain - Can cause tonsillitis & conjunctivitis. Diagnosis - Gram stained smear of urethral, cervical and rectal swabs (triple swab) - Culture necessary for sensitivity (may fail to grow if transport to the lab was delayed) - DNA based detection NAAT/NA hybridization tests Treatment Ceftriaxone 250mg single dose IM, Cefixim, Azithromycin, Spectinomycin, amoxycillin + probencid, Ciprofloxacin, Ofloxacin. 50% of gonorrhea & chlamydia occur concurrently so treat patient and partners for both infections (Doxycycline + ceftriaxone) Pelvic inflammatory disease (PID) PID is polymicrobial infection 80% of cases are triggered by STI Polymicrobial infection arising from endocervix (STI) → endometritis, salpingitis, (delicate tubes usually affected), oophoritis, pelvic peritonitis, hydrosalpinx, tubo-ovarian & pelvic abscess, parametrial infection, sometimes leading to perihepatitis → Fitz Hugh Curtis syndrome (violin string adhesions). Routes of infection: 1) ascend from vagina or cervix (STI) 2) introduced in to the upper tract (iatrogenic) e.g salpingitis tubal ligation 3) hematogenous e.g TB 4) spread from adjacent organs e.g. appendicitis 5) lymphatic spread Risk factors Multiple sexual partners, early coitarche, intercourse without barrier, previous PID, any intrauterine procedure (e.g IUD insertion, D&C, hysteroscope), vaginal douching, low seocioeconomic status Clinical features - Bilateral abdominal, pelvic pain, Deep dyspareunia, cervical excitation and adnexal tenderness on PV. - IMB, AUB, PCB - Abnormal vaginal discharge Inflammation of liver capsule with adhesion formation resulting in RUQ pain - Fever > 38C - Nausea, vomiting Normally fallopian tube cannot be detected in US except in ectopic and hydrosalpinx - RUQ pain / tenderness - Generalized peritonitis & sepsis if severe Differential diagnosis Ectopic pregnancy UTI Ovarian cyst complication Appendicitis IBS, IBD Psychosomatic pain Investigation - Blood: (WBC, ESR, CRP, B-HCG) - Microbiological: endocervical swab for gonorrhea culture & Chlamydia NAAT - GUE - HIV test, Syphilis serology - US, MRI or CT - Laparoscopy (diagnostic & therapeutic) Treatment Mild-moderate → outpatient, oral ATB: Ceftriaxone + Doxycycline ± metronidazole (gonorrhea, chlamydia & anaerobic cover respectively) or ofloxacine + metronidazole In patient treatment with parentral antibiotic if pregnant, HIV, does no response to oral medication, severely ill, nausea and vomiting, high fever, abscess or surgical emergencies (e.g., appendicitis) cannot be excluded. Parentral antibiotic (cephalosporins): Ceftriaxone 1g/day IV Cefotetan 2g + IV doxycycline 100mg (twice daily) Complication of PID RecurrentPID Ectopic pregnancy Tubal factor infertility Chronic pelvic pain Hydrosalpinx Tubo-ovarian abscess Fitz-Hugh–Curtis syndrome Female genital tract tuberculosis (FGTTB) Almost always secondary to pulmonary (commonest) or extra pulmonary TB, Primary FGTTB is from male genital TB. Mostly damage tubes → Infertility is the commonest presentation. (Fallopian tubes involvement 100%) -Vaginal examination: uterine enlargement (pyometra), adnexal tenderness, adnexal masses or ulcerative lesions in cervix, vagina or vulva, fistulae. R = Rifampicin Investigation I = Isoniazide CBC, ESR E = Ethanbutol Mantoux-tuberculin test P = Pyrazinamide Serology (HIV) Endometrial biopsy (in the premenstrual phase); for histopathological testing for granuloma Mycobacterial smear and Lowenstein-Jensen media culture of secretions from vagina, cervix, peritoneal fluid Imaging: CXR, US, CT, MRI Laparoscopy and Hysteroscopy Treatment 9 months RIEP or 6 months RIE, repeat endometrial sampling, twice ⊖ results 6 months apart means cure Herpes simplex virus Genital Herpes infection is a chronic lifelong viral infection caused by herpes simplex virus HSV-1 associated with oral lesions while type 2 is the cause of genital herpes Clinical features Itching or tingling sensations in the genital or anal area Small fluid-filled blisters that burst leaving small painful Ulcer, heal without scarring within 14-21 days Pain when passing urine over the open sores Retention of urine Flu-like symptoms, including fever. Diagnosis: it is clinical diagnosis, viral culture, PCR Treatment: bathing in salt water, analgesia, lignocaine, oral or topical Acyclovir (400mg orally twice daily for 5 days) Genital wart Common STI, caused by HPV, HPV 6, 11 associated with genital wart while HPV 16,18 linked to cervical cancer Clinical presentation Latent infection: no visible lesions , only diagnosed by DNA hybridization testing performed in the evaluation of an abnormal pap smear. Subclinical infections have lesions that are only visible during colposcopy Clinical infections are characterized by visible “warty” growths called condylomata acuminata on the vulva, vagina, cervix, urethra, and perianal area. Transmission of HPV can occur even when there are no visible lesion, condom maybe protective During pregnancy, condylomata may increase in number, size but transmission from mother to infant is rare. Treatment Surgical therapies (can be used in pregnancy): cryotherapy, surgical excision, electrocautery, laser vaporization Topical therapies (contraindicated in pregnancy): podophyllin cream, trichloroacetic acid (TCA) or bichloracetic acid (BCA), imiquimod cream, podofilox solution or gel Genital warts is not indication for C/S unless it is severe vaginal wart in which there is risk of neonatal laryngeal papillomatosis Syphilis (Treponema pallidium) STI but can also vertically transmit → IUFD & congenital syphilis (deafness, keratitis, abnormal teeth). Primary syphilis: chancre, develops in locations close to where bacteria typically enters the body: Chancre is a painless ulcers on the genitalia with inguinal LAP (any other genital ulcer is painful) Secondary syphilis: is a disseminated form → widespread papular rash over the trunk and extremities, fever, myalgias, LAP, sore throat and headache are common, It can lead to arthritis, glomerulonephritis, nephrotic syndrome and uveitis. One common manifestation is rough, reddish-brown spots on the bottoms of feet and on the palms of hands. Tertiary syphilis: multiorgan including cardiosyphilis and neurosyphilis, usually appear after many years. Latent period: subsequent asymptomatic months to years of latency. Diagnosis: Sample taken from ulcer examine under dark field microscope Blood test to detect antibody like fluorescent treponemal antibody FTA (sensitive and specific test) VDRL and rapid plasma reagin test RPR (non specific) Treatment: patient & partner - Procaine or Benzathine penicillin - Doxycyclin or Erythromycin if allergic to penicillin The bacteria is still sensitive to penicillin so it is rare now bcz people take penicillin as HIV It suppress the function of T- helper lymphocyte and macrophage Transmission: Direct contact with body fluids, most often semen or blood. Sexual contact Parenteral exposure (intravenous drug abuse and transfusions) Perinatal transmission (transmission across the placenta), at delivery or during breastfeeding. Diagnosis: By finding antibodies to gp 120, normal lymphocyte CD4 in the peripheral blood is 0.5%, the risk of AIDS development within one year if CD4 level drop to 0.2%, CBC show lymphopenia and thrombocytopenia Treatment: by Antiretroviral drugs (reduce the level of viruses so the CD4 lymphocyte rises) Other rare STI Chancroid is caused by Haemophilus ducreyi The lesions are painful and are usually accompanied by pelvic adenopathy, diagnosis is made clinically and confirmed by culture. Treatment is with azithromycin, 1 g orally in a single dose, or ceftriaxone 250 mg intramuscularly in a single dose. Granuloma inguinale (donovanosis) is caused by Calymmatobacterium granulomatis. The lesions are red and raised. Treatment is with doxycycline, 100 mg twice a day for a minimum of 3 weeks. Lymphogranuloma venereum is caused by C. trachomatis. Vesicles progress to bubo formation. Treatment is with doxycycline, 100 mg twice a day for at least 3 weeks.  Subfertility, Male infertility lectures together Pregnancy chance depends on frequency and timing of intercourse because sperm survive for 3 days, egg survive for 1 day, it increases with more months from 70% in half year to 80% in one year to 90% in two years. Couples having intercourse three times a week are three times more likely to conceive than couples having intercourse once a week. Sub-fertility: failure to conceive for 1 year of regular unprotected intercourse. Primary if never conceived or secondary if previously has conceived. Decreased ovarian reserve and age are major factors in reduced female fertility Factors affect natural conception rate Age: natural conception declines in female after 35 years (due to decline in oocyte quality and numbers) Smoking: reduces fertility in females and semen quality in males. Coital frequency: stress and anxiety affect libido, coital frequency Alcohol: excessive alcohol is harmful to the fetus, and can also affect sperm quality. Body weight: affect ovulation; women with (BMI) of > 29 or < 19 will have difficulty conceiving. Drugs: NSAIDs, cimetidine, sulphasalazine, androgen injections (affects sperm quality). Occupation: exposure to chemical and radiation Causes of subfertility Male 30% Female 30% Combined 10% Unexplained 30% Female cause: Ovary: PCOS is commonest,↓ ovarian reserve, hypogonadism (amenorrhea), pituitary causes as hyperprolactinemia, endocrine causes as thyroid disorder Tubal factor infertility: PID, endometriosis, adhesions due to previous pelvic/abdominal surgery. Uterine: fibroids (especially submucosal & intramural), endometrial polyp, anomalies, asherman. Cervical: Trauma (e.g. cryotherapy, conization), antisperm antibodies in mucus, DES syndrome, poor quality or quantity of mucus. Systemic: DM, thyroid, CKD, epilepsy, bowel disease. Male cause: Pre-testicular (hormonal) Testicular: trauma, surgery for undescended or torsion, varicocele, CTx, RTx, orchitis, epididymitis Post-testicular (obstructive, ED) Erectile dysfunction or problems with ejaculation Genetic as klinefelter Investigation of female infertility — Hormonal: FSH, LH, Estradiol, AMH (marker of ovarian reserve, decrease with age and undetectable in postmenopausal), midluteal progesterone If irregular cycle → TFT, Prolactin, testosterone. — TVUS — Tubal patency: HSG Hysterocontrast synography (HyCoSy) using ultrasound or recently 3D HyCoSy Invasive hysteroscope + laparoscope for dye test with methylene blue No test is available to assess tubal function tubal patency is not equivalent to tubal function Chlamydia testing should be offered prior to any uterine instrumentation. If will do ART (assisted reproduction technique) → Test for HIV, HBV, HCV. How to detect ovulation occurs or not? By 5 methods, the first two are most commonly used: 1- Ovulation predictor test (urine LH surge ⊕ 1-2 days before ovulation and stays ⊕ for 1 day, natural intercourse or artifical insemination should be done on day or a day after positive LH test, test OR salivary estrogen is raised) 2- Basal body temperature chart (taken immediately after waking up from at least 2 hours of sleep, before any movements, it rises half degree from ovulation to menses, but would remain high if pregnancy occur) 3- Ultrasound (check growth of follicle and and after ovulation, follicular cyst collapse (evidence of ovulation)) 4- Progesterone level (rise gradually after ovulation, peaks 7-10 days after ovulation, if not high → no ovulation or luteal phase deficiency) 5- Endometrial biopsy (taken 7-10 days after ovulation → secretory phase means normal ovulation) Leukocytospermia: > 1 million WBC/mL, mostly from epididymis, only 20% associated from bacteria and will resolve spontaneously. Investigation of male infertility SFA (need 2-4 days of abstinence of ejaculation, repeated after 3 months if abnormal to allow adequate time for spermatogenesis). Hormonal (if sperm 6 mmole/L. Brain symptoms improve with estrogen All women requiring HRT & have no contraindication Vaginal relaxation is not responsive to estrogen therapy alone Effect on Alzheimer, dementia and cognitive function not clear at this time Estrogen relieve symptoms associated with urogenital atrophy (atrophic vaginitis, dyspareunia treated with oral and vaginal estrogen, urinary symptom especially urgency improve with systemic, topical estrogen. 2- Prevention and treatment of osteoporosis Estrogen replacement after menopause act as antiresorptive, not approved for treatment of osteoporosis but appear to decrease risk of fracture in osteoporosis. Accelerate bone loss that occur after menopause can be prevented with: Early estrogen replacement (transdermal, oral) → 50% reduction in fracture risk. Adequate calcium intake (1000-1500mg) of calcium+ vitamin D required daily. Weight bearing exercise to stimulate bone formation and maintain muscle tone. Other anti resorptive agents used to treat osteoporosis include calcitonin, bisphosphonat, selective estrogen receptor modulate as raloxifine. Contraindications to HRT: related to effect of estrogen or metabolism of it: Absolute: Relative: Confirmed VTE Seizure disorder Neuro-ophthalmologic vascular disease High serum triglycerides Uncontrolled HTN Current gall bladder disease. Endometrial carcinoma Migraine headache Breast cancer. Fibroid Undiagnosed vaginal bleeding Benign breast disease Suspected pregnancy Chronic stable liver disease Acute hepatic disease Chronically unstable liver function Risk of HRT Endometrial cancer – estrogen therapy increase the risk of endometrial hyperplasia and cancer when used without progesterone. Cardiovascular disease – heart attack, stroke, and thromboembolism Breast cancer Regimes Unopposed estrogen: daily doses in women who are hysterectomized. Cyclic combined therapy: estrogen on days 1-25 of month, and progestogen for last 12 days of cycle. Sequential combined therapy: estrogen daily, and progestogen for 12-14 days every month. Continuous combined therapy: both given daily. Periodic or quarterly progestogen: given 14 days once every 3 month to reduce number of with drawal bleeding and progestin side effect. Transdermal patch: estrogen alone or combined with progesterone. Local (used intravaginally to treat symptoms of urogenital atrophy, dyspareunia): estrogen containing cream, tablet, patch, synthetic ring. Progestin IUD to protect endometrial tissue and avoid systemic side effect. Current agent Estrogen Conjugated estrogen Estrone sulfate Transdermally (patch) combined estrogen and progesterone Progestogen Medroxy progesterone acetate Natural oral micronized progesterone Prior to starting HRT, take detail history, examination, and investigation History Previous symptoms of menopause, it is impact on patient personal, domestic & occupational effeiciency. Family history of IHD, stroke , skeletal disease particularly osteoporosis, alzheimer disease History of gastrointestinal or liver disease that might interfere with estrogen therapy. Gynecological history (any medical, surgical intervention or presence of any condition that is estrogen dependent as endometriosis, fibroid or any irregular vaginal bleeding) Any history of benign or malignant breast diseases Examination: General (BP, breast, pelvic examination for any pelvic mass as fibroid or adenexial mass) Investigation Skeletal X-ray If there is risk of osteoporosis Mammography Any AUB should be investigated by U/S for endometrial Serum cholesterol level thickness , hysteroscopy & endometrial biopsy Pelvic U/S (abdominal & vaginal) Abnormal uterine bleeding should be investigated by D&C Estrodiol E2 Estron E1 Mode of treatment In HRT, only natural estrogen used (E2, E1, conjugated equine estrogen) which can be metabolized easily by body. E2 is largely converted in the liver to E1. The normal ratio of E2: E1 during premenopausal period is 2 : 1. Progesterone used are usually the least androgenic (medroxyprogesterone acetate & dydrogesterone because norethsteron & norgestrel have a potent androgenic effect → they will abolish the beneficial effect of estrogen on lipid & lipoprotein (androgens decrease HDL & increase LDL). Follow up: after 3 months, 6 months then annually. annual review include (BP, breast & pelvic examination) TREATMENT Not present in lecture Nonhormonal Treatment Lifestyle modification: physical activity (weight-bearing), reducing high coffee intake, smoking and excessive alcohol, adequate calcium intake (300 mL of milk), reducing medications that causes bone loss (corticosteroids). Supplementary calcium: Daily intake of 1–1.5 g can reduce osteoporosis and fracture. Vitamin D: Supplementation of vitamin D3 (1500–2000 IU/day) along with calcium can reduce osteoporosis and fractures. Exposure to sunlight enhances synthesis of cholecalciferol (vitamin D3) in the skin. Vitamin E reduces hot flash Bisphosphonates prevent osteoclastic bone resorption Denosumab: monoclonal antibody to RANK ligand. It inhibits osteoclast, bone resorption, reduce risk of fracture. Calcitonin inhibits bone resorption by inhibiting osteoclasts, simultaneously with vit D and calcium should be given. Selective estrogen receptor modulators (SERMs): raloxifene increase bone mineral density, reduce LDL and raise HDL level. Raloxifene inhibit estrogen receptors at the breast and endometrial tissues. Risks of breast cancer and endometrial cancer are therefore reduced. Raloxifene does not improve hot flashes or urogenital atrophy Bazedoxifene: It control vasomotor symptoms. it is SERM and is combined with conjugated equine estrogen. Clonidine, an α2 adrenergic agonist may be used to reduce the severity and duration of hot flashes. It is helpful where estrogen is contraindicated (hyperten-sion). Side effects are hypotension, dry mouth and constipation. Antidepressants (SSRI) as Paroxetine, venlafaxine, sertraline and fluoxetine, Side effects of (SSRIs) are: Nausea, headache, diarrhea, insomnia, fatigue and sexual dysfunction. Gabapentin is analog of GABA, effective to control hot flashes. Parathyroid hormone: Teriparatide is a recombinant parathyroid hormone. It increases osteoblast number, activity and reduces apoptosis of osteoblasts. Phytoestrogens containing isoflavones are found to lower the incidence of vasomotor symptoms, osteoporosis and cardiovascular disease. Soy protein: effective to reduce vasomotor symptoms. acts as SERM. Hormonal treatment Available Preparations for Hormone Therapy Principal hormone used in HT is estrogen (for woman who had hysterectomy), But in woman with intact uterus, only estrogen therapy leads to endometrial hyperplasia and even endometrial carcinoma. Addition of progestins for last 12–14 days each month can prevent this problem. Commonly used estrogens are conjugated estrogen (0.625–1.25 mg/day) or micronized estradiol (1–2 mg/day). Progestins used are medroxyprogesterone acetate (MPA) (1.5–5 mg/day), micronized progesterone (100–300 mg/day) or dydrogesterone (5–10 mg/day). Diagnosis of menopause Cessation of menstruation for consecutive 12 months during climacteric. Average age of menopause: 50 years. Appearance of menopausal symptoms ‘hot flash’ and ‘night sweats’. Vaginal cytology—showing maturation index of at least 10/85/5 (features of low estrogen). Serum estradiol: 40 mlU/mL (three values at weeks interval required)  Urinary incontinence Incontinence: Involuntary loss of urine Risk factors Women, old age, obesity, smoking, FMHx of incontinence, DM and neurological disease muscles in bladder and urethra lose some of their strength with increasing age Types: Stress (increase abdominal pressure as coughing): due to pelvic floor or nerve damage from childbearing. Urge (overactive bladder, accompanied by frequency, urgency, and nocturia): cystitis, neurological disorder, DM. Mixed (both of stress, urge) Overflow: underactivity of detrusor muscle, associated with retention, bladder does not empty completely, and “dribbling” of urine occurs Passive (extraurethral via fistula -> continuous): congenital, surgery, obstructed labor, TB, radiation. treated by surgery Functional (problem getting to toilet): Arthritis, depression, Alzheimer, dementias Reflex (detrusor spasm with no urgency and can't stop it: Neurological spinal or supraspinal reflex incontinence (Multiple sclerosis , CVA, dementias, Alzheimer’s disease and Parkinson’s disease.) Diagnosis History: (urinary symptoms, previous urologic surgery, CNS or spinal cord disorders, PMHX, PSHX, DHx) Examination: exacerbating conditions (COPD, obesity, abdominal mass), hypermobility, prolapse, neurologic disorder. Use of medications as diuretics, antihypertensives, caffeine, alcohol, anticholinergics, nicotine Investigation decongestants, and psychotropics MSU: GUE, C&S. Postvoid residual urine volume: by US or catheterization, typically it is 30 degree change with coughing urethral hypermobility is present Urodynamic testing: Cystometrogram during filling & voiding to determine the type, measure pressure within the bladder and abdomen during bladder filling and emptying Cystoscope: to examine urethral and bladder mucosa for any abnormalities as diverticula, neoplasms. Treatment — Treatments of exacerbating factors (cough, constipation, obese) "stress" — Pelvic floor rehabilitation (kegel exercise) "stress & urge or overactive bladder" — Pessaries for stress — Drugs (mainstay for urge): anti spasmodic as tolterodine, alpha adrenergic, estrogen (improve urgency, dysuria but not leakage), HRT does not reduce incidence of urinary symptoms in postmenopausal women — Surgery (mainstay for stress) like: Injection of bulking agent around the urethra (collagen) Retropubic urethropexy Transvaginal needle procedures Suburethral sling: TVT & TOT  Genital prolapse Normal uterus is anteverted (cervix on vagina), anteflexed (uterus on cervix) see below picture Genital prolapse is the descent of one or more of the genital organ (urethra, bladder, uterus, rectum, douglas pouch or rectouterine pouch) through the fasciomuscular pelvic floor below their normal level. Vaginal prolapse can occur without uterine prolapse but uterus cannot desent without carrying vagina with it. Causes and Predisposing factors Primary cause is weakness of the supporting structures of the uterus and vagina, including utero-sacral ligament, cervical ligament, perineal muscles & fascia either from trauma of childbirth, congenital weakness, postmenopausal atrophy Injury of the pelvic floor Types: Vaginal Prolapse 1- Anterior wall prolapse: Prolapse of upper part of anterior vaginal wall with base of bladder is called cystocele Prolapse of lower part of anterior vaginal wall with urethra is called urethrocele Complete anterior vaginal wall prolapse is called cysto-urethrocele 2- Posterior wall prolapse: It is called rectocele if anterior wall of rectum is also prolapsed with middle third of the posterior vaginal wall It is called entrocele (hernia of the pouch of douglas) if the upper third of the posterior vaginal wall descends lined by the peritoneum of the Douglas pouch and containing loops of the intestine 3- Vault prolapse: descent of vaginal vault, where the top of vagina descend, or inversion of vagina after hysterectomy (more likely to occur after subtotal than after total hysterectomy). Uterine prolapse 1- Utero-vaginal: uterus descend first followed by vagina: This usually occurs in cases of virginal and nulliparous prolapse due to congenital weakness of the cervical ligaments. 2- Vagino-uterine: vagina descends first followed by the uterus:This usually occurs in cases of prolapse resulting from obstetric trauma. Degrees of uterine prolapse 1st: cervix desent below its normal level on straining but does not protrude from the vulva. the external os of the cervix is at the level of the ischial spines. 2nd: cervix protrudes from the vulva on straining or at level of introitus. 3rd: (Complete procidentia) the whole uterus is completely prolapsed outside the vulva and the vaginal wall becomes most completely inverted over it. Enterocele is usually present. (dekubitus ulcer due to friction & less blood supply). Symptoms of prolapse Sensation of weakness in the perineum particularly towards the end of the day. A mass which appears on straining and disappears when she lies down. Urinary symptoms: Urgency and frequency (only in day), stress incontinence, inability to urinate unless anterior vaginal wall is pushed upwards by patient's finger. frequency, dysuria day & night in case of cystitis. Rectal symptoms not so marked: heaviness in rectum and constant desire to defecate, hemorrhoids. Backache, congestive dysmenorrhoea and menorrhagia are common. Leucorrhoea is caused by the congestion and associated by chronic cervicitis. Pelvic Organ Prolapse Quantitative (POP-Q) Scoring: 0: No descent of pelvic organs 1: Leading edge of the prolapse does not descend 1 cm above the hymenal ring 2: extends to ‡ 1 cm around hymen. 3: Extend beyond 1 cm beyond the hymen. 4: Complete eversion of vagina Treatment of prolapse Prophylactic (prevention) Proper antenatal care: The pelvic floor should be both strong and elastic, prevent constipation Proper intra-natal care: Avoid straining and forceps during first stage. episiotomy should be done when indicated to avoid hidden perineal lacerations; and avoid fundal pressure to deliver the placenta. Proper post-natal care: Accurate repair of perineal tears or episiotomies, postural treatment, correction of retroversion during the puerperium with the use of knee chest position or pessaries, encourage pelvic floor exercises, prevent constipation & care of general health to prevent debility and bad general health. Palliative treatment Actual treatment: physiotherapeutic lines indicated in: Early and mild cases. As a prophylactic measure after delivery. Alleviation in more severe cases (pre-and post operative treatment). Aims out of PT treatment: to establish awareness of function pubococcygeus and pelvic supports, to strength the pubococcygeus muscle. Palliative treatment by wearing ring pessary is indicated in the following conditions: 1. Slight degrees of prolapse in young patients. Operation should be postponed until the woman has had a sufficient number of children as long as the symptoms are mild. 2. Prolapse of the uterus in early pregnancy. The pessary is worn until the end of the fourth month until size of the uterus will be sufficient to prevent its descent. 3. Contraindications to operations as lactation, severe cough , or patients refusing surgical repair. 4. Bad surgical risks as old patient with advanced diabetes or severe hypertension. Surgical Treatment Posterior Colporrhaphy (repair) Anterior & Posterior Colporrhaphy for 1st degree prolapse. Manchester operation for 2nd degree prolapse. Vaginal Hysterectomy for 3rd degree (procedincia).