Unit 3 SG Ch 25 PDF - Female Reproductive System

**CHAPTER 25 -- Alterations of the Female Reproductive System** **Understand the different uterine tumor types.** **Leiomyomas** (myomas or uterine fibroids) - Benign smooth muscle tumors in the myometrium - The most common benign tumors of the uterus (affecting as many as 70-80% of all...

**CHAPTER 25 -- Alterations of the Female Reproductive System** **Understand the different uterine tumor types.** **Leiomyomas** (myomas or uterine fibroids) - Benign smooth muscle tumors in the myometrium - The most common benign tumors of the uterus (affecting as many as 70-80% of all women) - Most remain small, asymptomatic, and clinically insignificant - Prevalence increases in women age 30-50, but decreases with menopause **Cause:** - Unknown - size appears to be related to estrogen, progesterone, growth factors, angiogenesis, and apoptosis **Location:** - occur in the fundus of the uterus in multiples, or singly throughout **Classification:** - subserous, submucous, or intramural (according to their location within various layers of the uterine wall) **Clinical manifestations:** - abnormal uterine bleeding, pain, pressure on nearby structure - May distort uterine cavity and increases uterine surface area which can explain increased bleeding **Evaluation:** - bimanual examination - uterine enlargement and irregular, nontender nodularity of the uterus - confirm diagnosis with pelvic sonography or MRI **Treatment:** - dependent on symptoms, tumor size, age, reproductive status, overall health, women's preference **What are the signs of puberty in girls and boys? What delays puberty?** +-----------------------------------+-----------------------------------+ | **Puberty** is the onset of | | | sexual maturation and differs | | | from adolescence. | | +===================================+===================================+ | **Adolescence** is the stage of | | | human development between | | | childhood and adulthood. | | +-----------------------------------+-----------------------------------+ | **GIRLS:** begins at about 8-9 | **BOYS:** begins at about 11 | | years of age  with thelarche | years of age  occurs with | | (**breast development, one of the | increased weight and body mass | | first signs of puberty in | index | | girls**) | | +-----------------------------------+-----------------------------------+ | **Influences on timing:** | | | genetics, environment, ethnicity, | | | general health, and nutrition | | | | | | - Reproductive maturation | | | involves the **hypothalamic | | | pituitary-gonadal (HPG) | | | axis,** the **CNS**, and the | | | **endocrine system** | | | | | | - A sequential series of | | | hormonal events promotes | | | sexual maturation as puberty | | | approaches | | | | | | - About 1 year before puberty | | | in girls  increase in | | | frequency and amplitude of | | | nocturnal pulses of | | | gonadotropin secretion, LH, | | | and FSH, and an increased | | | response in the pituitary to | | | GnRH  stimulates **gonadal | | | maturation | | | ([gonadarche)]** | | | with estradiol secretion in | | | girls and testosterone | | | secretion in boys | | | | | | - **Estradiol causes breast | | | development (thelarche), | | | maturation of the | | | reproductive organs, | | | (vagina, uterus, ovaries) | | | and fat deposit in hips | | | in girls**. | | | | | | - **Estrogen and increased | | | production of growth | | | factors cause rapid | | | skeletal growth in boys | | | and girls.** | | | | | | - **Testosterone causes | | | growth of the testes, | | | scrotum, and penis**. A | | | positive feedback loop is | | | created with | | | gonadotropins stimulating | | | the gonads to produce | | | more sex hormones. The | | | most important hormonal | | | effects occur in the | | | gonads. The testes begin | | | to produce mature sperm | | | and are capable of | | | fertilizing an ovum. | | +-----------------------------------+-----------------------------------+ | **In females, the ovaries begin | **Male puberty is complete with | | to release mature ova**. **Female | the first ejaculation that | | puberty is complete with the | contains mature sperm** | | first ovulatory menstrual | | | period**; | | | | | | however, this can take up to 1 to | | | 2 years after menarche | | +-----------------------------------+-----------------------------------+ | **Adrenarche** is the increased | | | production of adrenal androgens, | | | (dehydroepiandrosterone and | | | androstenedione. which is | | | converted ton testosterone and | | | estrogen) prior to puberty, which | | | occurs in both sexes, and is | | | exhibited by axillary and pubic | | | hair growth and body odor. | | | Puberty is complete when an | | | individual is capable of | | | reproduction. | | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **DELAYED PUBERTY - GIRLS** | | +===================================+===================================+ | **Define** | No clinical signs of puberty in | | | girls by age 13 in girls. | +-----------------------------------+-----------------------------------+ | **Clinical diagnosis** | Can be made in the absence of | | | menarche by age 15 or 16 | +-----------------------------------+-----------------------------------+ | **Risks** | - Although delayed, puberty may | | | have significant psychosocial | | | implications and carries a | | | risk of inadequate skeletal | | | development and | | | mineralization | | | | | | - Puberty is a time of rapid | | | skeletal growth, with the | | | majority of bone development | | | and mineralization achieved | | | during adolescence. | | | | | | - Estrogen plays a major role | | | in this process  lack of | | | circulating estrogen puts | | | individuals at risk of | | | inadequate bone density in | | | adulthood | +-----------------------------------+-----------------------------------+ | **Physiologic** | Hormonal levels are normal and | | | the | | **(Constitutional) Delay** | hypothalamic-pituitary-gonadal | | | (HPG) axis is intact  maturation | | | is happening slowly | | | | | | Tends to be familial (less common | | | in girls than boys), frequently | | | diagnosed retrospectively once | | | pubertal progression is complete | | | | | | 30% of girls with delayed puberty | | | ultimately progressed through | | | normal and spontaneous puberty | | | | | | **Treatment:** expectant | | | management or initiation of | | | hormone therapy in small doses to | | | promote pubertal development and | | | diminish the risk of poor | | | skeletal growth and | | | mineralization. | +-----------------------------------+-----------------------------------+ | **Functional Hypogonadotropic** | **Treatment:** correction of the | | | underlying condition, with a | | **Hypogonadism** | possible initiation of hormone | | | therapy if a prolonged recovery | | **(FHH)** | is projected. | +-----------------------------------+-----------------------------------+ | **Disruption in the** | Human gonadal function is | | | partially controlled by | | **HPG axis** | luteinizing hormone (LH) and | | | follicle-stimulating hormone | | | | | | - The G protein-coupled | | | receptor 54 (GPR54) has been | | | identified as the gatekeeper | | | gene for activation of the | | | GnRH axis. GPR54 is required | | | for the normal function of | | | this axis | | | | | | - Legand kisspeptin-1 may act | | | as a neurohormonal regulator | | | of the GnRH axis | | | | | | - Believed to be feedback | | | inhibition by sex steroids | | | and presumably other CNS | | | pathways may be involved. | | | | | | **Treatment:** synthetic GnRH or | | | sex hormone administration, or | | | both, and may be lifelong. | +-----------------------------------+-----------------------------------+ | **Evaluation** | - Lab workup, including x-ray | | | studies for bone age, | | | measurement of thyroid | | | function, serum levels of | | | prolactin and plasma gonadal | | | and adrenal steroids, | | | radioimmunoassay of plasma | | | gonadotropins, and screening | | | for systems disorders should | | | be completed | | | | | | - Adolescents with high | | | gonadotropin levels  | | | karyotype to rule out genetic | | | causes | | | | | | Adolescents with low gonadotropin | | | levels  need skull imaging to | | | rule out pituitary or other CNS | | | infiltrate or tumor | +-----------------------------------+-----------------------------------+ | **Goal of Treatment** | Development of secondary sex | | | characteristics and fertility and | | | the promotion of bone growth and | | | mineralization | +-----------------------------------+-----------------------------------+ | **Treatment** | Depends on the cause | | | | | | - Insufficient sex hormone | | | secretion  hormone | | | replacement therapy | | | (estrogen) | +-----------------------------------+-----------------------------------+ +-----------------------+-----------------------+-----------------------+ | **DELAYED PUBERTY - | | | | BOYS** | | | +=======================+=======================+=======================+ | **Define** | No clinical signs of | | | | puberty in boys by | | | | age 14 | | +-----------------------+-----------------------+-----------------------+ | **Clinical | Early diagnosis and | | | diagnosis** | treatment recommended | | | | | | | | **(embarrassed by | | | | sexual immaturity**  | | | | **self-esteem | | | | issues)** | | +-----------------------+-----------------------+-----------------------+ | **Physiologic | **Define:** hormonal | | | (Constitutional)** | levels are normal and | | | | the | | | **Delay** (95% of | hypothalamic-pituitar | | | cases) | y-gonadal | | | | (HPG) axis is intact | | | |  maturation is | | | | happening slowly | | | | | | | | Tends to be familial | | | | (more common in boys) | | | | | | | | - Physiologic delay | | | | is difficult to | | | | distinguish from | | | | isolated | | | | gonadotropin | | | | deficiency; | | | | diagnosed | | | | retrospectively | | | | once pubertal | | | | progression is | | | | complete | | | | | | | | **Treatment:** | | | | expectant management | | | | or initiation of | | | | hormone therapy in | | | | small doses to | | | | promote pubertal | | | | development and | | | | diminish the risk of | | | | poor skeletal growth | | | | and mineralization. | | +-----------------------+-----------------------+-----------------------+ | **Functional** | Central nervous | Kallmann syndrome | | | system defects (GnRH | | | **Hypogonadism** | deficiency) | Bardet-Biedl syndrome | | | | | | (Deficient FSH/LH) | Craniopharyngioma | Prader- Willi | | | | syndrome | | | GPR54 mutations | | | | | Marijuana use | | | Hemochromatosis | | | | | Pituitary | | | Hypopituitarism | adenoma/tumor | | | | | | | | Prolactinomas | +-----------------------+-----------------------+-----------------------+ | | **Treatment:** | | | | correction of the | | | | underlying condition, | | | | with a possible | | | | initiation of hormone | | | | therapy if a | | | | prolonged recovery is | | | | projected. | | +-----------------------+-----------------------+-----------------------+ | **Chronic or | Chronic renal disease | Gonadal dysgenesis: | | Systemic** | | | | | Cystic fibrosis | - Turner syndrome | | **Conditions** | | (genetic | | | Diabetes mellitus | karyotype 45, XO) | | | | | | | Excessive exercise | Bilateral gonadal | | | | failure: | | | Hypothyroidism | | | | | - Autoimmune | | | Hematologic diseases | | | | | - Congenital | | | Irritable bowel | anorchia | | | diseases | | | | | - Postsurgical, | | | Poor nutrition: | postirradiation, | | | eating disorders, GI | postchemotherapy | | | diseases, poverty | | | | | Traumatic or | | | | infectious | +-----------------------+-----------------------+-----------------------+ | **Disruption in the** | - The G | | | | protein-coupled | | | **HPG axis** | receptor 54 | | | | (GPR54) has been | | | (5% of cases) | identified as the | | | | gatekeeper gene | | | | for activation of | | | | the GnRH axis. | | | | GPR54 is required | | | | for the normal | | | | function of this | | | | axis | | | | | | | | - Legand | | | | kisspeptin-1 may | | | | act as a | | | | neurohormonal | | | | regulator of the | | | | GnRH axis | | | | | | | | - Believed to be | | | | feedback | | | | inhibition by sex | | | | steroids and | | | | presumably other | | | | CNS pathways may | | | | be involved. | | +-----------------------+-----------------------+-----------------------+ | **Evaluation** | - Lab workup, | | | | including x-ray | | | | studies for bone | | | | age, measurement | | | | of thyroid | | | | function, serum | | | | levels of | | | | prolactin and | | | | plasma gonadal | | | | and adrenal | | | | steroids, | | | | radioimmunoassay | | | | of plasma | | | | gonadotropins, | | | | and screening for | | | | systems disorders | | | | should be | | | | completed | | | | | | | | - Adolescents with | | | | **high** | | | | gonadotropin | | | | levels  | | | | karyotype to rule | | | | out genetic | | | | causes | | +-----------------------+-----------------------+-----------------------+ | **Goal of Treatment** | Development of | | | | secondary sex | | | | characteristics and | | | | fertility and the | | | | promotion of bone | | | | growth and | | | | mineralization | | +-----------------------+-----------------------+-----------------------+ | **Treatment** | | | +-----------------------+-----------------------+-----------------------+ **What hormone is linked to obesity and early puberty in females?** The is an association between obesity and earlier puberty in girls, perhaps from **higher estrogen levels** related to **gonadotropin and estrogen** secretion. Girls with low body fat, reduced body weight, and intense exercise may experience delayed maturation. Though leptin is not the trigger for puberty onset, it plays an important permissive role. **What is PCOS and what does it cause? Clinical manifestations? Treatment? Causes? Pathophysiology?** **Most common cause of anovulation** and ovulatory dysfunction; leading cause of infertility in the U.S. Associated with metabolic dysfunction dyslipidemia, insulin resistance, and obesity **Defined** at least two of the following features: - irregular ovulation - elevated levels of androgen (ex: testosterone) - appearance of polycystic ovaries on ultrasound---polycystic ovaries do not have to be present (their presence alone does not establish the diagnosis) **Pathophysiology of PCOS**: strong genetic component suspected - Hyperandrogenic state is a cardinal feature - Glucose intolerance/insulin resistance run parallel to and markedly aggravate the hyperandrogenic state severity of s/s of PCOS +-----------------------------------------------------------------------+ | **Clinical manifestations of PCOS**: | +=======================================================================+ | - Usually appear within 2 years of puberty (may present after a | | variable period of normal menstruation function and possibly | | pregnancy) | | | | | | | | - Obesity | | | | - Hirsutism | | | | - Menstrual disturbance | | | | - Oligomenorrhea | | | | - Amenorrhea | | | | - Regular menstruation | | | | - Hyperandrogenism | | | | - Infertility | | | | | | | | - Increased insulin | | | | - Increased androgens (testosterone, androstenedione) | | | | - Increased dehydroepiandrosterone (DHEA) (occurs in 50% of women) | | | | - Increased luteinizing hormone (LH) (genetic variant LH-β subunit) | | | | - Increased prolactin | | | | - Increased leptin, especially in obesity | | | | - Decreased sex hormone--binding globulin (SHBG) | | | | - Suggested decreased insulin-like growth factor 1 (IGF-1) | | receptors on theca cells | | | | - Possible decreased estrogen receptors (intraovarian and along | | hypothalamic-pituitary axis) | | | | | | | | - Dyslipidemia---increased low-density lipoproteins (LDLs), | | decreased high-density lipoproteins (HDLs), increased | | triglycerides | | | | - Diabetes mellitus (30% of women with or without obesity will | | develop type 2 diabetes mellitus by age 30) | | | | - Cardiovascular disease; hypertension | | | | - Endometrial hyperplasia and carcinoma (anovulatory women are | | hyperestrogenic) | | | | | | | | - Sleep apnea | | | | - Nonalcoholic fatty liver disease | | | | - Women with PCOS are at increased risk of gestational diabetes | | mellitus, pregnancy-induced hypertension, preterm birth, and | | perinatal mortality | +-----------------------------------------------------------------------+ **Goals of Treatment:** - Reversing s/s of androgen excess - Instituting cyclic menstruation - Restoring fertility - Ameliorating any associated metabolic or endocrine or both disturbances **Treatment of PCOS**: - First-line combined oral contraceptives for management of s/s and to establish regular menses - Overweight or obese women lifestyle modifications (regular exercise and weight loss) - Women with insulin resistance, or those women who do not respond to contraceptive therapy insulin sensitizer Metformin - If oral contraceptives are not used and pregnancy is not desired progesterone therapy is recommended to oppose estrogen's effects on the endometrium (means to initiate monthly withdrawal bleeding) **What is the difference between primary and secondary amenorrhea?** +-----------------------+-----------------------+-----------------------+ | - It differs from | - **Pregnancy is | **[Compartment | | delayed puberty | the most common | II:]** | | in that most | condition to | | | cases of delayed | exclude before | **Disorders which | | puberty require | further | involve the ovary and | | on reassurance, | evaluation.** | are often linked with | | but when the | | genetic | | diagnosis of | thyroid disorders, | abnormalities.** | | primary | hyperprolactinemia, | | | amenorrhea is | HPO interruption | **These include | | reached, a | secondary to | gonadal dysgenesis | | thorough | excessive exercise, | (Turner Syndrome) or | | evaluation is | stress, weight loss | androgen | | needed. | and polycystic ovary | insensitivity | | | syndrome (PCOS). | syndrome (AIS).** | +-----------------------+-----------------------+-----------------------+ **Know pathophysiology, etiology, clinical manifestations, diagnostics, treatment and complications of endometriosis.** +-----------------------+-----------------------+-----------------------+ | **DEFINE** | Endometriosis: | | | | presence of | | | | functioning | | | | endometrial tissue or | | | | implants outside the | | | | uterus. | | | | | | | | These ectopic (out of | | | | place) tissues | | | | respond to hormonal | | | | fluctuations of the | | | | menstrual cycle just | | | | as normal endometrial | | | | tissue does. | | | | | | | | Women with | | | | endometriosis are at | | | | greater risk for | | | | cancers, especially | | | | ovarian cancer. | | +=======================+=======================+=======================+ | **ETIOLOGY** | - *Implantation of | | | | endometrial cells | | | \*\*no genetic | during | | | disposition has been | **retrograde | | | documented | menstruation***  | | | | menstrual fluids | | | | move through the | | | | fallopian tubes | | | | and into the | | | | pelvic cavity | | | | (occurs in almost | | | | all women, but | | | | all women don't | | | | develop | | | | endometriosis) | | | | | | | | - *Impaired | | | | cellular and | | | | humoral immunity* | | | | alterations in | | | | cytokine and | | | | growth factor | | | | signaling have | | | | been identified | | | | | | | | | | | | | | | | - Cytotoxic T-cell | | | | and natural | | | | killer cell | | | | activity is found | | | | to be depressed | | | | | | | | - Autoimmune | | | | response is also | | | | suspected | | +-----------------------+-----------------------+-----------------------+ | **PATHOPHYSIOLOGY** | - Inflammation, | | | | triggering a | | | | cascade of | | | | cellular | | | | inflammatory | | | | mediators, | | | | including | | | | cytokines, | | | | chemokines, | | | | growth factors, | | | | and protective | | | | factors such as | | | | leukocyte | | | | protease | | | | inhibitor and | | | | superoxide | | | | dismutase. | | | | | | | | - The inflammation | | | | may lead to | | | | fibrosis, | | | | scarring, | | | | adhesions, and | | | | pain. | | | | | | | | Endometrial implants | | | | can occur throughout | | | | the body, but the | | | | most common sites of | | | | implantation are the | | | | ovaries, uterine | | | | ligaments, | | | | rectovaginal septum, | | | | and pelvic | | | | peritoneum. | | +-----------------------+-----------------------+-----------------------+ | **RISK FACTORS** | Family history, | | | | menstrual cycle | | | | abnormalities (long | | | | cycles, period before | | | | ages 12, having few | | | | days in between | | | | periods), never | | | | giving birth, | | | | conditions that | | | | interfere with normal | | | | menstrual flow | | | | (increased estrogen, | | | | fibroids or polyps, | | | | structural | | | | abnormality of | | | | uterus/cervix/vagina) | | +-----------------------+-----------------------+-----------------------+ | **CLINICAL** | - 25-40% of women | | | | with infertility | | | **MANIFESTATIONS** | have | | | | endometriosis | | +-----------------------+-----------------------+-----------------------+ | **EVALUATION / | | | | DIAGNOSTICS** | | | +-----------------------+-----------------------+-----------------------+ | **GOAL OF TREATMENT** | | | +-----------------------+-----------------------+-----------------------+ | **TREATMENT** | Mifepristone | - laparoscopic | | | | removal of | | | | endometrial | | | | implants with | | | | conventional or | | | | laser techniques | | | | | | | | - presacral | | | | neurectomy for | | | | severe | | | | dysmenorrhea | +-----------------------+-----------------------+-----------------------+ **Etiology of cervical intraepithelial carcinoma (CIN) and cervical Ca.** It is established that cervical cancer is almost **exclusively caused by cervical human papillomavirus (HPV) infection**. 1. **Precancerous dysplasia, also called cervical intraepithelial carcinoma (CIN) and cervical carcinoma in situ (CIS), is a more advanced form of these cell changes** 2. Importantly, cervical dysplasia can be detected noninvasively through examination of the cervical cells. If dysplasia is detected early, treatment is available to prevent invasive cancer. 3. Most sexually active women will contract HPV at some point in life Infection with "high-risk" (oncogenic) types of HPV is a necessary precursor to development of cervical dysplasia, otherwise known as the precancerous cell changes that lead to invasive cancer. **What is the BRCA1 gene?** More than two-thirds of breast cancer cases occur in women older than 55. Some women **younger than 45** may have a **higher risk** for getting breast cancer if they have the following risks: 1. Close relative diagnosed with breast cancer or ovarian cancer when they were younger than 45, especially if there is more than one 2. **Alterations in certain breast genes (BRCA1 and BRCA2), or having relatives with these alterations** 3. Ashkenazi Jewish heritage 4. Treatment with radiation therapy to breast or chest during childhood or early adulthood 5. Diagnosed with breast cancer or other breast health problems A small proportion of breast cancers (5-10%) is the result of highly penetrant dominate genes. The most important of the breast cancer genes are BRCA1 and BRCA2. 1. **BRCA1: is located on chromosome 17, is a tumor-suppressor gene; therefor any mutation in the gene may inhibit or retard its suppressor function, leading to uncontrolled cell proliferation** a. A family history of both breast cancer and ovarian cancer increases the risk that an individual with breast cancer carries a **BRCA1** mutation b. Carriers are at high risk for ovarian cancer c. Risks for breast & ovarian cancers are not equal in each carrier & have been found to vary based on cancer type, age onset, and position of mutation. d. Other genetic and environmental factors modify cancer risk in mutation carriers e. Options for mutation carriers include surveillance