Womens Reproductive Health PDF

**[Week 1: Lecture 1 & 2: COCs]** **Identify hormonal changes that occur during the female reproductive cycle.** **Discuss the features, indications, and adverse effects of combined oral contraceptives.** **Counsel on the safe and appropriate use of combined oral contraceptives.** During the fol...

**[Week 1: Lecture 1 & 2: COCs]** **Identify hormonal changes that occur during the female reproductive cycle.** **Discuss the features, indications, and adverse effects of combined oral contraceptives.** **Counsel on the safe and appropriate use of combined oral contraceptives.** During the follicular phase, leading up to the ovulation stage the estrogen level increases. Then in the lutheal phase, the estrogen level decreases as the progesterone level starts to increase. COC all contains estrogen and progestogen which inhibit ovulation, reduce receptivity of endometrium to implantation and thicken cervical mucus to from barrier to sperm. COC are indicted in contraception, acne, menstrual disorders, endometriosis, and premenstrual syndrome.  [COC counselling ] - Most COC contains 21 days active pills and 7 inactive, designed so that women commence on the placebo tablet. - Yaz and zoely have 24 days active and 4 day inactive pill - Qlaira had 26 days active pills and 2 days inactive - Seasonique had no inactive, 84 combined pills and 7 mono EE pills. - 7 consecutive days of active pills are necessary to reliably prevent ovulation and hormone free interval should not exceed 7 days. [COC missed pill advice ] - Week 1 of active tablets: riskiest time to miss, if \>48 hr since last active tablet or first active \>24 hr late. Take EC if had intercourse, take most recent missed pill, discard other missed pills and continue as normal. Use barrier methods for 7 days. - Week 2 of active tablets: safest time to miss, if \>48 hr since last active tablet, take most recent missed pill, discard other missed pills and continue as normal. NO EC required and use barrier methods for 7 days. - Week 3 of active tablets: somewhat risky time to miss, if \>48 hr since last active tablet, take most recent missed pill, discard other missed pill, skip the hormone free interval and straight onto NEW ACTIVE pack. NO EC required and use barrier methods for 7 days. **Identify target patients for the varying combined oral contraceptives.** **[EXTRA NOTES]** - Breast cancer: contraindicated as hormonally sensitive, may worsen prognosis - Migraine: may be exacerbated or relieved, contraindicated with aura \>35 years old. - Diabetes: increase risk of thrombosis, avoid use of end organ damage, effects on glucose metabolism. - BMI \>30 kg/m2: Risk of VTE increase - Cardiovascular: hypertension increase risk of MI and stroke, avoid use if BP is not controlled. - History of VTE: contraindicated - Smoking: increase risk of VTE and cardiovascular events. \35 years avoid COC. - Surgery: increase risk of thromboembolism, stop COC 4 weeks before surgery and restart COC \>2 weeks after mobilisation. - Pregnancy: no increased risk of birth defects from inadvertent use however, theoretical risk with cyproterone containing COCs. - Breastfeeding: estrogen may decrease milk supply (avoid use and recommend progest-only) - Postpartum: delay use until 21 days post-partum or 42 days if VTE risk. Drugs interactions with COCs - Estrogens and progestogens are metabolised by CYP3A4, therefore taking a COC within 4 weeks of drugs that induce CYP3A4 may lead to contractive failure for an example: Anti-epileptics (carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate), St john's Wort or antibiotics (griseofulvin, rifampicin, rifabutin). - If concomitant COC use with enzyme-inducing drugs: use monophasic COC with levonorgestrel and ethinylestradiol and increase ethinylestradiol to 50 mcg daily. Use extended cycles with reduced hormone-free intervals of 4 days, and additional method of contraception (e.g. condoms), as there is still a risk of contraceptive failure (which may not be accompanied by breakthrough bleeding) Tricycling COCs - Running 3 cycles of active hormone pills together, omitting the placebo pills for 2 packs out of 3 (9 continuous weeks of oral contraceptive). - Pill free period may be reduced to 4 days and patient may het a drug withdrawal bleed. +-----------------------------------+-----------------------------------+ | **[Week 2: Lecture 3: POPs and | | | LARCs]** | | +===================================+===================================+ | **Discuss the features, | **Explain the features, | | indications and adverse effects | indications and adverse effects | | of progestogen-only | of long-acting reversible | | contraceptives (POPs)** | contraceptives. Advise on the | | | safe and appropriate use of | | | vaginal, implant, intrauterine | | | and IM depot contraceptives. | | | (LARC)** | +-----------------------------------+-----------------------------------+ | - Progesterone only | LARCs are administered less than | | contraceptives contain no | ONCE a month and are highly | | estrogen: thicken cervical | effective, cost effect (except | | mucous, impeded the passage | vaginal rings) and are relatively | | of sperm, change endometrium | independent of user adherence. | | reducing the potential for | | | implantation and may suppress | [Prolonged Hormonal | | LH surge and inhibit | Contraception: ] | | ovulation. | | | | Progestogen Depot (PBS: | | - Indicated when estrogen is | medroxyprogesterone 150mg/mL | | not tolerated or is | injection | | unsuitable, mainly used when | (Depo-provera/ralovera)) | | women are breastfeeding as it | | | will not affect the quality | - First dose given within 5 | | or quantity of milk. | days after start of menstrual | | | cycle then replacement of | | - Traditional POPs contained | individual IM depot given | | levonorgestrel or | every 12 weeks. | | norethisterone and new POP | | | contains drospirenone. | - Not immediately reversible | | | may take \>6 months, | | | therefore delayed return of | | | menstrual periods. | | | | | | - Associated with weight gain, | | | avoid in overweight | | | adolescents | | | | | | - Postpartum: if used in the | | | first 6 weeks may cause heavy | | | and irregular bleeding | | | | | | - Small decrease in BMD, | | | especially in the first few | | | years. Partial recovery of | | | bone loss after stopping | | | therefore encourage patient | | | to stop smoking, weight | | | bearing exercise and adequate | | | intake of calcium and | | | vitamin D. | | | | | | - NOT FIRST LINE IN \50 years (due | | | to effect on BMD) | | | | | | Progestogen Implant (PBS: | | | Etonogestrel implant 68mg | | | (Implanon NXT)) | | | | | | - 4cm rod inserted subdermal | | | into upper non-dominant arm | | | once every 3 years. | | | Detectable on X-ray. | | | | | | - NOT suitable with CYP3A4 | | | inducers consider LNG IUD or | | | DMPA or copper IUD. | | | | | | - Immediately reversible upon | | | removal, no negative effect | | | on BMD, no proven increase in | | | weight. | | | | | | - Safe to start any time in the | | | postpartum period and changes | | | in bleeding pattern | | | (irregular/prolonged bleeding | | | or no periods). | | | | | | Progestogen Intrauterine systems | | | (PBS: levonorgestrel 52mg IUD | | | (Mirena)) | | | | | | - MOA: Progestogen released has | | | local effect on endometrium, | | | preventing implantation, | | | thickening of cervical mucous | | | impedes passage of sperm, | | | ovulation is suppressed in | | | some women and hormonal side | | | effects may occur | | | | | | - Indication: contraception, | | | HRT/MHT and menorrhagia. NOT | | | recommended for emergency | | | contraception. | | | | | | | | | | | | - Replaced every 5 years and is | | | inserted within 7 days start | | | of menstrual cycle or 6 weeks | | | after delivery. | | | | | | - Mirena may be used until | | | menopause without being | | | replaced if inserted in \>45 | | | year old patient to treat | | | heavy menstrual bleeding. | | | | | | Progestogen Intrauterine systems | | | (PBS: levonorgestrel 19.5mg IUD | | | (Kyleena)) | | | | | | - Indication: contraception | | | | | | - Device is smaller than Mirena | | | and narrower insertion tube | | | therefore less pain and | | | designed for nulliparous | | | women or those with smaller | | | uterus. | | | | | | Combined vaginal Ring | | | Contraceptive (NON-PBS: | | | ethinyloestradiol 2.7mg and | | | etonogestrel 11.7mg (NuvaRing)) | | | | | | - Insert ring into vagina for 3 | | | weeks, remove for 1 week | | | break and period should start | | | within 2-3 days of ring | | | removal. Continue to insert | | | new ring after 1 week break | | | even if period has not | | | stopped. | | | | | | - Same contraindications and | | | precautions as COCs. | | | | | | - Vaginal antifungals have no | | | interfere with its efficacy. | | | | | | [Non-Hormonal Contraception | | | ] | | | | | | Copper Intrauterine Device | | | | | | - Interfere with sperm movement | | | and implantation. Is replaced | | | every 5 years to 10 years | | | | | | - Used for contraception and | | | emergency contraception. | +-----------------------------------+-----------------------------------+ | **Counsel on the safe and | | | appropriate use of progesterone | | | only contraceptives, including | | | missed-pill advice** | | +-----------------------------------+-----------------------------------+ | PBS: Levonorgestrel 30mcg and | | | Norethisterone 350mcg | | | | | | - Taken continuously without a | | | break as there are no | | | inactive pills. Maximal | | | effect between 3 and 21 hours | | | after ingestion. Use | | | additional contraception for | | | 48 hours prior to sexual | | | intercourse. | | | | | | - Missed pill advice: 3-hour | | | window of protection when | | | taking pills at the same | | | time. | | | | | | | | | | | | - Take it as soon as possible | | | and then take the next pill | | | at the usual time. Resume | | | normal pill taking and use | | | other contraception such as | | | condoms. | | | | | | - HOWEVER, if a pill is more | | | than 3 hours overdue and | | | intercourse has occurred, EC | | | is needed. | | | | | | | | | | | | - Vomiting, severe diarrhoea | | | missed pills and other | | | medication may stop the pill | | | from working. Efficiency will | | | be restored after POP has | | | been taken daily for the next | | | 48hours, therefore use other | | | contraceptive method in the | | | meantime. | | | | | | NON- PBS: Drospirenone 4mg | | | | | | - Safe in breastfeeding, | | | hypertension, migraine, | | | smoking and weight neutral. | | | However, some VTE risk and | | | drug interactions with ST | | | John's wort and | | | anti-epileptic medicine. | | | | | | - 28 pill pack containing 24 | | | active pill and 4 inactive | | | pills, could expect | | | withdrawal bleed during the | | | HFI. | | | | | | - Start taking the tablet at | | | the white active pill for the | | | first 24 days then a green | | | inactive pill for the last 4 | | | days. Then without a break in | | | daily tablet intake continue | | | onto a new pack. | | | | | | - Missed pill advice: tablets | | | intake should not exceed 24 | | | hours | | | | | | | | | | | | - Days 1-7: take missed pill | | | ASAP and barrier methods for | | | 7 days | | | | | | - Days 8-17: Take missed pill | | | ASAP, no other protection | | | required | | | | | | - Days 18-24: Take missed pill | | | ASAP, skip placebo pills and | | | begin new active pack, no | | | other protection required. | | +-----------------------------------+-----------------------------------+ | **[EXTRA NOTES]** | | +-----------------------------------+-----------------------------------+ | Contraceptive Choice | | | | | | - [Adolescents]: | | | COC, etonogestrel implant, | | | IUD (acceptable) and DMPA is | | | LEAST preferred due to BMD. | | | | | | - [Postpartum:] No | | | contraception required for 21 | | | days after delivery; | | | therefore, barrier methods | | | may be used. Progesterone | | | pill ONLY may be used, or IUD | | | inserted \4weeks. | | | COC or NuvaRing should be | | | delayed until \>21 days | | | postpartum due to increase | | | thrombosis risk | | | | | | - [Breastfeeding:] | | | Progesterone only, barrier | | | methods and IUD can all be | | | used. Avoid COC and NuvaRing | | | as it may decrease milk | | | supply but can be considered | | | if BF is established and | | | other contraceptive methods | | | are unacceptable. | | | | | | - [\>40 years:] POP | | | can be used until menopause; | | | COC can be used if no CV risk | | | and \ | | | | | | - Timing between UPSI and use | | | of EC - UPSI 0-96 hours: UPA | | | or LNG **[OR]** | | | UPSI 96-120 hours: UPA ONLY. | | | | | | - Patient weight: BMI \26kh/m2 | | | or weight \>70 kg: UPA or LNG | | | double dose (3mg) off label | | | or copper IUD (preferred) | | | **[OR]** | | | BMI \>30kg/m2 or | | | weight \>85kg: refer. | | | | | | - Potential drug interactions: | | | CYP3A4 (copper IUD preferred | | | and LNG double dose) | | | **[OR]** patient | | | with severe asthma treated | | | with oral glucocorticoids | | | (LNG preferred, NOT UPA as | | | may worsen asthma if UPSI | | | is \>96 hours than REFERRAL. | | | | | | | | | | | | - MUST gain patient consent to | | | ask personal questions: | | | | | | | | | | | | - Is EC for your own use? Time | | | since unprotected | | | intercourse? | | | | | | - When was your last menstrual | | | period? Is it usually | | | regular? | | | | | | - Any other incident of | | | unprotected intercourse in | | | the same cycle? Any chance | | | that you might already be | | | pregnant? | | | | | | - Do you have any other medical | | | condition? Current breast | | | cancer? Unexplained vaginal | | | bleeding? | | | | | | - Other medication? Hormonal | | | contraception? Breastfeeding? | | | | | | - To select the most effective | | | EC for you, I just need to | | | know your weight and height. | | | | | | Emergency contraction | | | counselling: | | | | | | - Oral EC is not 100% | | | effective, take as soon as | | | possible after UPSI and | | | repeat dose if vomiting or | | | diarrhea occurs within 3 | | | hours. EC becomes less | | | effective if further | | | unprotected sex has occurred | | | after taking EC. Can be used | | | any time of the menstrual | | | cycle however, LNG and UPA | | | should not be used together. | | | | | | - EC does not protect against | | | STI, encourage patient to | | | consult a medical or sexual | | | health practitioner if they | | | think they may be at risk of | | | STI. | | | | | | - AE: N/V, headache, abdominal | | | pain, dysmenorrhea, breast | | | tenderness, abnormal vaginal | | | bleeding or spotting. | | | | | | - Next menstrual period maybe | | | earlier or later than | | | expected and seek further | | | medical advice if menstrual | | | period within 3 weeks has not | | | started, therefore pregnancy | | | test may be recommended | | | especially with patient | | | resuming cyproterone | | | containing COC (risk of | | | feminisation of male foetus). | | | | | | - Recurrent use of EC: LNG has | | | no limit recurrent use | | | however, ulipristal | | | manufacturer does not | | | recommend repeated use within | | | the same menstrual cycle as | | | concern about hepatoxicity. | | | | | | Ongoing contraceptive advice: | | | | | | - After taking EC | | | Levonorgestrel: oral | | | contraceptive pill can be | | | resumed or started | | | immediately however barrier | | | methods should be used "until | | | 7 active tablets of COC or | | | drospirenone POP have been | | | taken OR 3 active tablets of | | | LNG or norethisterone POP | | | have been taken OR 7 days of | | | vaginal ring OR 7 days after | | | implant or DMPA." | | | | | | - After taking EC ulipristal: | | | progestogen-containing | | | contraception can be resumed | | | after 5 days, however barrier | | | methods should be used during | | | the 5 days and ("same as EC | | | LNG") | +-----------------------------------+-----------------------------------+ | **Briefly discuss the role of | | | copper IUDs following unprotected | | | intercourse** | | +-----------------------------------+-----------------------------------+ | Cooper IUD can be inserted up to | | | 120 hours (5 days) after UPSI but | | | requires insertion by trained | | | practitioner and timely insertion | | | may be impractical. Advantages of | | | providing contraction for the | | | rest of the cycle or for the next | | | 5-10 years if desired. (other | | | notes above) | | +-----------------------------------+-----------------------------------+ | **[Week 2: Lecture 5: Medical | | | Abortion ]** | | +-----------------------------------+-----------------------------------+ | **Discuss medical abortion, | **Provide counselling to patients | | including the therapeutic use of | who are prescribed mifepristone | | mifepristone with misoprostol** | with misoprostol for medical | | | abortion** | +-----------------------------------+-----------------------------------+ | - Mifepristone + misoprostol | Step 1: Mifepristone Counselling: | | (MS-2 step) composite pack is | | | used for medical abortion. | - Antiprogesterone, softens and | | Indicated in termination of | dilates the cervix to | | first or second trimester | increase sensitivity to | | pregnancy up to nine weeks | misoprostol. | | gestation. Alternative to | | | surgical abortion, safe, cost | | | effective and more acceptable | | | to patients. | - Take single tablet orally and | | | if vomiting occurs within 1 | | - Contraindicated in | hour of ingestion, dose must | | anticoagulation, haemorrhagic | be repeated. | | disorder, IUD that can't be | | | removed, long term use of | Step 2: Misoprostol Counselling: | | oral glucocorticoid, travel | | | time to hospital \>2 hours in | - Synthetic prostaglandin E1 | | 14 days after taking | derivative analogue which | | mifepristone and confirmed or | induce contractions. | | suspected ectopic pregnancy. | | | | - Commenced after 36-48 hours | | - Precautions: severe anaemia, | of mifepristone. Take four | | diabetes required insulin, | tablets buccally held in | | epilepsy, unstable asthma or | place for 30 minutes than | | long-term preventer therapy. | swallowed residual material. | | | AE: Nausea, headaches, fever, | | | diarrhoea. Premedication with | | | antiemetics and NSAID | | | recommended 30-60 minutes | | | before misoprostol. | | | | | | - Expected effects: cramping | | | 1-4hrs of taking misoprostol, | | | bleeding/blood clots, | | | emotional and conceptus can | | | be seen with later | | | gestations. | | | | | | - For 7 days patient should | | | avoid: sex, tampons, | | | swimming, bath or spa and | | | refer if any signs of | | | infection such as pelvic | | | pain, abdominal pain or | | | tenderness and unusual | | | vaginal discharge. | | | | | | Patient must present to ER if | | | very heavy bleeding, passing | | | clots size of lemon, feeling | | | faint, severe abdominal or pelvic | | | pain, pain in tips of the | | | shoulders. A medical abortion | | | follows up to ensure the abortion | | | is complete a serum HCG or low | | | sensitivity urine pregnancy test | | | is done. | +-----------------------------------+-----------------------------------+ | **[Week 3: Lecture 6: Women's | | | Reproductive Health Conditions | | | ]** | | +-----------------------------------+-----------------------------------+ | **Discuss the signs, symptoms and | | | management of:** | | +-----------------------------------+-----------------------------------+ | Premenstrual Syndrome (PMS) | - PMS occurs during the luteal | | | phase of the menstrual cycle | | | as there is complex | | | interaction between ovarian | | | hormones, serotonin and GABA | | | which may involve enhanced | | | responsiveness to normal | | | fluctuating hormones, rather | | | than change in hormone | | | production. | | | | | | - Symptoms occurs up to 14 days | | | before and resolve within 3 | | | days of the beginning of a | | | period. They can include | | | depressed mood, anxiety, | | | irritability, feeling | | | overwhelmed, decreased | | | interest in usual activities, | | | lack of energy, hypersomnia | | | or insomnia, change in | | | appetite, breast tenderness, | | | bloating. | | | | | | - Management: lifestyle changes | | | (diet, style changes, | | | exercise, rearrangement of | | | workload), encourage patient | | | to keep a diary, intake of | | | calcium, vitamin B6 | | | (pyridoxine), COCs | | | (monophasic) may be effective | | | in PMS and SSRIs. | +-----------------------------------+-----------------------------------+ | Premenstrual Dysphoric Disorder | - A severe and disabling form | | (PMDD) | of PMS characterised by | | | severe mood disturbances | | | which disrupts the woman's | | | life. | | | | | | - COCs with drospirenone and | | | low dose ethinylestradiol for | | | 24 days of 28-day cycle may | | | help | | | | | | - SRRIs (fluoxetine and | | | sertraline) may be | | | considered: dosed daily or | | | cyclically starting 14 days | | | before and until the first | | | full day of the period. | +-----------------------------------+-----------------------------------+ | Amenorrhoea | - Absence of a menstrual period | | | in women of reproductive age | | | | | | - Primary: periods haven't | | | started by 14 and no other | | | sexual characteristics | | | (breasts, pubic hair) OR | | | period haven't started by 16 | | | even with other sexual | | | characteristics. | | | | | | - Secondary: periods stop for | | | approximately 6 months (due | | | to pregnancy or | | | breastfeeding), often due to | | | hormonal disruption. | | | | | | - Potential causes: weight | | | change, emotional stress, | | | excessive exercise, | | | imperforate hymen, | | | lactational amenorrhoea and | | | pregnancy, hormonal disorders | | | (hypothyroidism, PCOS, | | | hyperprolactinaemia), | | | hypogonadism (risk of | | | long-term estrogen deficiency | | | on bone density and | | | cardiovascular health). | +-----------------------------------+-----------------------------------+ | Dysmenorrhoea | - Occurrence of painful | | | menstruation associated with | | | increased production PGE2 and | | | PGF2a. | | | | | | - Primary dysmenorrhoea: pain | | | begins in teenage years | | | usually before or soon after | | | the onset of period and lasts | | | for 8-72 hours. No | | | demonstrable pathology and | | | not presented during | | | anovulatory cycles. | | | | | | - Secondary dysmenorrhoea: | | | associated with pelvic | | | pathology (fibroids, | | | endometriosis, PID, polyps) | | | and occurs later in life | | | with/out menorrhagia. Changes | | | in pain (congested or | | | bloated) and upon pelvic | | | examination abnormalities or | | | intermenstrual bleeding | | | presented. | | | | | | - Management: NSAIDs (naproxen, | | | mefenamic and ibuprofen), | | | paracetamol, COCs, Mirena. | +-----------------------------------+-----------------------------------+ | Menorrhagia | - Abnormally heavy menstrual | | | bleeding, all patients would | | | be assessed for iron | | | deficiency anaemia. | | | | | | - Treatment choice: depends on | | | woman's age, parity, | | | coexisting medical | | | conditions, need for | | | contraception and if HMB is | | | ovulatory (sometimes occurs | | | with period pain and PMS) or | | | anovulatory (may occur with | | | PCOS, low BMI or excess | | | exercise **[OR]** | | | irregular, occurs \40 yrs.) | | | | | | - Management: nonhormonal | | | options are second line | | | treatment (NSAIDS, tranexamic | | | acid) **[OR]** | | | Hormonal options are | | | considered first line (LNG | | | IUD, COCs or vaginal ring or | | | POP or depot | | | medroxyprogesterone) | | | **[OR]** Nondrug | | | treatment may include | | | endometrial ablation and | | | hysterectomy. | +-----------------------------------+-----------------------------------+ | Endometriosis | - Presence of endometrial | | | tissue outside the uterus | | | which attaches to other | | | organs in the abdominal | | | cavity such as ovaries and | | | fallopian tubes. | | | | | | - Symptoms: recurrent pelvic | | | pain or chronic pain, | | | dysmenorrhoea, deep | | | dyspareunia, heavy, irregular | | | or extended bleeding, | | | ovulation pain or infertility | | | and cyclical bladder or bowel | | | symptoms. | | | | | | - Complications: adhesions, | | | adenomyosis and endometriomas | | | (requires surgery) | | | | | | - Management: individualised | | | due to age, symptoms, extent | | | of disease and pregnancy | | | plans. Management can include | | | laparoscopic surgery | | | (preferred in infertility), | | | NSAIDS, hormonal treatments | | | (COCs, POPs, GnRH analogues | | | (nafarelin, goserelin), GnRH | | | antagonists (relugolix, | | | estradiol and | | | norethisterone), aromatase | | | inhibitors (anastrozole and | | | letrozole are reversible, | | | however, exemestane is | | | irreversible and therefore | | | contraindicated in patients | | | desiring future conception)) | +-----------------------------------+-----------------------------------+ | **[Week 3: Lecture 7: PCOS and | | | Fertility ]** | | +-----------------------------------+-----------------------------------+ | **Describe the pathogenesis, | **Detail the basic menstrual | | signs and symptoms, treatment and | cycle and principles of the | | management options of Polycystic | female reproductive system** | | Ovary Syndrome (PCOS)** | | +-----------------------------------+-----------------------------------+ | PCOS is caused from hereditary | GNRH release hypothalamus acting | | component or lifestyle related | on the anterior pituitary which | | such as overweight or lack of | produces FSH in the follicular | | physical activity. Majority of | phase of the cycle. The ovaries | | women with PCOS have a form of | produce estrogen which causes | | insulin resistance and | positive feedback to the anterior | | compensatory hyperinsulinemia. | pituitary where the LH triggers | | So, when insulin is stimulated | the release of an egg from the | | from the pancreas the ovarian | ovary causing ovulation. Once | | production of androgen increases. | ovulation has passed, in the | | In addition, hyperinsulinemia | luteal phase where progesterone | | inhibits the production of sex | production occurs, the corpus | | hormone binding globulin which | luteum is left behind for | | increases circulating free | possible implantation of a | | testosterone levels causing | foetus. If fertilisation has | | insulin to prevent ovulation | occurred, a zygote is formed and | | either by directly affecting | about 5-6 days an implantation | | follicular development or by | into the endometrium will occur. | | indirectly increasing | | | intraovarian androgen levels or | | | altering gonadotropin secretion. | | | | | | Signs of PCOS throughout life | | | stage: | | | | | | Life stage Features | | | ------------- ----------------- | | | ------------------------ | | | Childhood Premature puberty | | | Adolescence Hirsutism | | | Adulthood Subfertility/infe | | | rtility OR GI problems | | | Later life Tyle 2 diabetes O | | | R CV disease | | | | | | PCOS management: | | | | | | - Assess psychological | | | wellbeing in all individuals | | | with PCOS and should address | | | long term condition such as | | | type 2 diabetes, CV risk | | | factors or endometrial | | | cancer. | | | | | | - Lifestyle changes such as | | | weight loss, exercise, diet | | | and ongoing screening for | | | fasting blood glucose should | | | be lifelong as this can | | | increase ovulatory function, | | | decrease long term CV | | | effects, improve insulin | | | sensitivity and reduce | | | diabetes risk. | | | | | | - Metformin is ONLY used as | | | part of treatment for | | | subfertility OR patient are | | | at a great risk of type two | | | diabetes OR impaired glucose | | | tolerance as it can improve | | | menstrual regularity, reduce | | | insulin resistance and reduce | | | serum free testosterone and | | | may induce ovulation with/out | | | clomifene. | | | | | | - Menstrual irregularities or | | | amenorrhoea are treated with | | | CoCs which suppress androgen | | | production and regulate | | | menstrual disturbances | | | | | | - If androgenisation is severe, | | | patient is treated with | | | anti-androgens such as | | | spironolactone and | | | cyproterone acetate. | | +-----------------------------------+-----------------------------------+ | | **Discuss methods of detecting | | | and maximising fertility** | +-----------------------------------+-----------------------------------+ | | - Anti- Mullerian hormone | | | testing | | | | | | - [Cervical mucus | | | changes:] Fertile | | | mucus is stretchy, slippery, | | | consistency of egg white. | | | | | | - [Salica | | | microscopy:] Fern | | | like patterns in saliva can | | | sometimes be observed in days | | | leading up to ovulation, | | | expensive but reusable. | | | | | | - [Basal body | | | temperature] | | | rises slightly on the day | | | before ovulation therefore a | | | chart of temperatures can be | | | used to predict ovulation. | | | Accurate and precise, | | | temperature taken after | | | waking. | | | | | | - [Ovulation predication via | | | urine LH | | | detection:] | | | Pre-ovulation predication of | | | LH surge using an instream | | | urine detection device. | | | | | | - [Luteal phase progesterone | | | testing:] Post | | | ovulation progesterone | | | testing conducted 7 days | | | before the predicted date of | | | period. | +-----------------------------------+-----------------------------------+ | **[Week 3: Lecture 8: | | | Infertility]** | | +-----------------------------------+-----------------------------------+ | **Describe the principles and | **Discuss the rationale and risk | | causes of infertility in males | of infertility treatments, | | and females** | including ovulation induction and | | | assisted conception.** | +-----------------------------------+-----------------------------------+ | Male infertility | Male infertility empirical | | | therapy includes hormones and | | - Structural or anatomical | hormone antagonists | | problems | (gonadotrophins, androgens, | | | antiestrogens) in unexplained | | - Vasectomy | infertility | | | | | - Sperm production disorders: | - Gonadotrophin therapy | | low sperm count, motility, | indicated only in Gn | | morphology | deficient men, to induce | | | spermatogenesis. | | - Immune system may produce | | | antibodies which attack and | - IVF techniques used in severe | | weaken their own sperm | persistent oligospermia | | | | | Female infertility | - Glucocorticoids can improve | | | sperm quality | | - Age: quality of oocytes | | | declines and less chance of | Ovulation induction aim to | | conceiving naturally | develop single oocyte with the | | | help of pharmacotherapy | | - Tubal disease: fallopian | (clomifene, letrozole or | | tubes are blocked or damaged | gonadotropins). A high risk of | | due to scar tissue, | induction is multiple follicles, | | infections or tubal ligation, | therefore careful monitoring is | | this prevents fertilisation. | essential. Another potential risk | | Treatment: Surgical | is ovarian hyperstimulation | | procedures OR IVF to bypass | syndrome where it can cause | | blockage. | patient severe abdominal | | | discomfort, renal insufficiency, | | - Endometriosis | coagulation disorders and include | | | fatal renal failure or | | - Anovulation causes: Class 1 | venous/arterial thrombosis. | | hypothalamic/ pituitary, | | | class II PCOS OR class III | Before ovulation induction: | | premature ovarian failure. | exclusion of pregnancy and normal | | | male semen analysis is required. | | | In amenorrhoeic women, | | | norethisterone or | | | medroxyprogesterone acetate is | | | used to induce uterine bleeding | | | which may make the endometrium | | | more suitable for implantation | | | and help the specialist choice of | | | ovulation induction drug such as | | | clomifene, letrozole and | | | gonadotropins. | | | | | | - Letrozole 2.5 to 5mg daily | | | for 5 consecutive days is | | | more effective, if ovulation | | | does not occur increase dose | | | for the next 2 cycles or | | | consider other drugs. | | | | | | Assisted production technologies | | | (ART) | | | | | | - In Vitro fertilisation | | | procedure (IVF, ZIFT, TET, | | | PROST) requires formation of | | | zygotes or embryos outside | | | the body with/out ICSI. | | | Process involves less or no | | | ovarian stimulation, egg | | | retrieval, fertilisation, | | | embryo culture, transfer of | | | embryos to uterus. | | | | | | - In Vivo (IUI and GIFT): rely | | | on vivo fertilisation, where | | | sperm are washed before | | | insertion. | | | | | | - Down regulation (GnRH | | | analogues, GnRH antagonists) | | | | | | - Superovulation | | | (Gonadotrophins (FSH)) | | | | | | - Oocyte maturation | | | (Gonadotrophins (LH or HCG)) | | | | | | - Progesterone supplementation | +-----------------------------------+-----------------------------------+ | **Detail patient counselling on | | | clomifene.** | | +-----------------------------------+-----------------------------------+ | Clomifene is a competitive | | | antagonist of estrogen receptors | | | in hypothalamus which blocks | | | negative feedback to pituitary | | | and increase pituitary | | | gonadotrophins which induces | | | ovulation. | | | | | | Clomifene 50mg ONCE daily for 5 | | | consecutive days staring between | | | day 2 to 5 of the menstrual | | | cycle. NOTE: 25mg may be | | | sufficient for those with lower | | | BMI and if ovulation does not | | | occur increase does over the next | | | 2 cycles, then consider other | | | drugs. Use for \ | | | | | Perimenopause: transition period | - Systemic estrogen (with/out | | before menopause, lasts an | progesterone) | | average of 5 years and experience | | | many of the physical and | - Low dose COCs -- preferred | | emotional changes associated with | until 50 years of age. | | menopause. Irregular menstruation | | | due to no corpus luteum, | - Clonidine | | therefore low progesterone | | | levels. However, remaining | - SERMS: bazedoxifene | | estrogen production proliferates | (available in combination | | endometrium which results in | with conjugated estrogens and | | menorrhagia. | added to reduce endometrial | | | cancer risk due to unopposed | | Menopause: Permanent cessation of | estrogens [OR] | | menstruation for at least 12 | raloxifene (used to prevent | | consecutive months. Occurs when | and treat postmenopausal | | all ovarian follicles are | osteoporosis) | | depleted and ovarian estrogen | | | production ceases. Factors | | | influencing the age of menopausal | | | symptoms (40-55 yrs): genetic | - Treatment may be considered | | predisposition and ovarian | if MHT is contraindicated: | | cystectomies. | | | | | | - Rationale for drug use is to | | | relief symptoms such as | - Antidepressant: gabapentin OR | | vasomotor symptoms, vaginal | low dose SSRIs OR SNRIs | | dryness and dyspareunia. | (venlafaxine and paroxetine | | | most effective) | | - Before starting treatment | | | lifestyle changes such as | - Fezolinitent (Veoza): first | | smoking cessation. Alcohol | class non hormonal treatment | | reduction and weight loss may | for vasomotor symptoms (under | | reduce symptoms in some | evaluation by TGA) | | women. Regular exercise and | | | avoid triggers (hot drinks) | **[Vaginal Atrophy | | may be helpful. | ]** | | | | | | - Estrogen receptors located in | | | vagina, vulva and urethra. | | | Decrease in estrogen | | | production leads to atrophy | | | of tissues such as decrease | | | in subcutaneous fat and | | | elasticity and paleness and | | | thinning of vaginal | | | epithelium which leads to | | | diminished distensibility and | | | reduced secretion. | | | | | | - Symptoms: vaginal dryness, | | | pruritus, tears or bleeding, | | | painful urination, painful | | | sexual intercourse, | | | alkalinisation of vaginal pH | | | (creating a favourable | | | environment for bacterial | | | colonisation) | | | | | | - Treatment aims to induced | | | proliferation of epithelium | | | and decreases in vaginal pH | | | | | | | | | | | | - intravaginal moisturisers | | | | | | - systemic MHT | | | | | | - intravaginal estrogens. | | | | | | | | | | | | - Alternative treatment for | | | women who cannot or do not | | | wish to use even low dose | | | vaginal estrogen | | | | | | | | | | | | - Vaginal moisturisers: | | | lubricants, replens, aci jel | | | restore, vagisil intimate | | | moisturisers. | | | | | | - Test vaginal pH: canestan or | | | vagicare. | | | | | | - Restore Vaginal pH: vagicare, | | | aci-jel, multi-gyn. | | | | | | **[Urethral | | | syndrome]** | | | | | | - Estrogen receptors located on | | | trigone of the bladder. | | | Estrogen deficiency leads to | | | tissue atrophy and loss of | | | pelvic tone. | | | | | | - Symptoms: Stress incontinence | | | (involuntary loss of small | | | volume of urine caused by | | | increase abdominal pressure), | | | urge incontinence | | | (involuntary loss of large | | | volume of urine). | | | | | | - Treatment aims to improve | | | urinary frequency and urgency | | | | | | | | | | | | - pelvic floor exercise, | | | | | | - systemic MHT | | | | | | - intravaginal estrogen | | | | | | **[Osteoporosis ]** | | | | | | - Gradual loss of bone mass | | | compromising the bone | | | strength leading to fractures | | | after minor falls/ injuries | | | | | | - Risk factors: slender, | | | sedentary females, Caucasian | | | or decent, smoking/alcohol | | | use, low intake of calcium | | | and vitamin D, family | | | history, chronic use of | | | steroids. | | | | | | - Treatment: Tibolone | | | | | | **[Coronary Heart disease | | | treatment ]** | | | | | | - Diet, exercise, with/out | | | pharmacological drug therapy. | | | | | | - Control of other | | | complications: diabetes, | | | hypertension and | | | hypercholesterolemia. | | | | | | - Smoking cessation, moderation | | | in alcohol consumption, | | | stress reduction | | | | | | - Estrogen replacement therapy | | | (ERT) OR combined MHT | +-----------------------------------+-----------------------------------+ | **Discuss the risks and benefits | | | of menopausal hormone replacement | | | (MHT), formerly hormone | | | replacement therapy (HRT)** | | +-----------------------------------+-----------------------------------+ | [Initiation of menopause | | | treatment:] when | | | symptoms are disruptive, | | | treatment may be required during | | | perimenopause | | | | | | [Pre-treatment | | | tests:] dull | | | gynaecological history and | | | examination, mammography, blood | | | pressure, blood lipids, complete | | | blood examination, thyroids | | | stimulating hormone and bone | | | density. | | | | | | [MHT treatment depends on several | | | factors:] nature and | | | severity of menopausal symptoms, | | | impact of symptoms on daily | | | activities, individual health | | | profile of patient | | | | | | [MHT | | | systemic | | | contraindications:] | | | | | | - Aged over 60 years | | | | | | - Previous or active | | | thromboembolic disorder | | | | | | - Unexplained uterine bleeding | | | | | | - Severe liver disease | | | | | | - Uncontrolled hypertension | | | | | | - Breast cancer or another | | | estrogen-dependent tumour. | | | | | | - Cerebrovascular or coronary | | | artery disease. | | | | | | [MHT systemic oral | | | contraindications:] | | | | | | - Risk factors for VTE: | | | obesity, smoking and | | | thrombophilia. | | | | | | - Risk factors for CV disease: | | | hypertension, previous CV | | | disease, insulin resistance, | | | diabetes, obesity, smoking. | | | | | | - Elevated triglycerides | | | | | | - Liver disease or gall bladder | | | disease. | | +-----------------------------------+-----------------------------------+ | **[Detail the suitable | | | therapeutic options for managing | | | the various menopausal | | | symptoms]** | | +-----------------------------------+-----------------------------------+ | [MHT Routes of Administration | | | ] | | | | | | - Oral: Relatively inexpensive, | | | convenient and well | | | tolerated, however some AE | | | (e.g. VTE and stoke) are | | | higher than transdermal | | | | | | - Transdermal: Avoid first pass | | | effects allows smaller doses, | | | reducing AE of nausea and | | | stroke, increase skin | | | irritation. | | | | | | - Vaginal preparation | | | (intravaginal estrogen): | | | First choice for urogenital | | | symptoms | | +-----------------------------------+-----------------------------------+ | | MHT drug choices | | | | | | - Estrogen-only MHT: | | | recommended post | | | hysterectomy, no history of | | | endometriosis and estrogen is | | | continuous. Help relieve | | | symptoms caused by reduced | | | endogenous estrogen. | | | | | |  | | | | | |  | +-----------------------------------+-----------------------------------+ | MHT drug choices | MHT drug choices | | | | | - Intravaginal estrogen for | - Combined MHT (estrogen + | | urogenital symptoms. OR used | progestogen): recommended in | | in women for whom systemic | women with an intact uterus | | estrogen therapy is | to reduce risk of endometrial | | contraindicated or | hyperplasia. May be cyclical | | ineffective. Women with | or continuous. | | vaginal dryness who have a | | | history of breast cancer | - Progestogens: combined or | | should try nonhormonal | dosed separately to reduce | | preparations before using | endometrial cancer risk | | estrogen intravaginally. If | associated with unopposed | | long term, add a 12-day | estrogen | | course of progestin every | | | 6-12months. | - Combined MHT -- sequential | | | (cyclical) | |  | | | | | | | | | | - Continuous estrogen (dose | | | titrated according to | | | symptoms) plus progestogen | | | for at least 10-14 days a | | | month OR for 14 days every 3 | | | months. | | | | | | - Withdrawal bleed expected | | | after progestogen stops, use | | | until 12-18 months after last | | | menses | | | | | | - For perimenopausal women or | | | early posy menopause. | | | | | |  | | | | | |  | +-----------------------------------+-----------------------------------+ | MHT drug choices | | | | | | - Combined MHT -- continuous | | | | | | | | | | | | - Continuous estrogen plus | | | continuous progestogen. Defer | | | until 12-18 months after last | | | menses and may stimulate | | | endometrium less likely to | | | cause hyperplasia than | | | sequential regimens. | | | | | |  | | +-----------------------------------+-----------------------------------+ | MHT drug choices: Tibolone | | | (livial, livilan, xyvion) | | | | | | - MAO: Estrogenic effect on | | | vagina, bone and | | | thermos-regulatory centres in | | | brain. | | | Progestogenic/anti-estrogenic | | | on breast and endometrium. | | | | | | - Indication: Relief of | | | vasomotor symptoms (short | | | term), prevention of | | | postmenopausal osteoporosis | | | when fracture risk is high | | | and alternative treatment is | | | inappropriate and may have | | | positive effect on libido. | | | | | | - Dose: 2.5 mg daily; not | | | started until 12 months after | | | last period OR immediately | | | after surgical menopause. | | | | | | - Contraindications: avoid use | | | in \70 years, avoid if | | | increase stroke risk and | | | breast cancer, hormone | | | dependent cancers, SLE, | | | coronary artery disease, | | | cerebrovascular disease, VTE, | | | severe liver disease. | | | | | |  | | +-----------------------------------+-----------------------------------+ | Other pharmacological management | | | | | | - SERMS: bazedoxifene | | | (available in combination | | | with conjugated estrogens) | | | inhibits stimulating effects | | | of estrogen on the | | | endometrium and reduce | | | endometrial cancer risk due | | | to unopposed estrogens. | | | Indicated for moderate to | | | severe vasomotor symptoms in | | | women with an intact uterus. | | | [OR ] | | | | | | - SERMS: Raloxifene (used to | | | prevent and treat | | | postmenopausal osteoporosis | | | and breast cancer in | | | high-risk postmenopausal | | | women) estrogen agonist on | | | bone and lipoprotein | | | metabolism and estrogen | | | antagonist on uterine and | | | breast tissue. Increases bone | | | mineral density, decrease | | | total cholesterol and LDL, | | | does not stimulate