ABORTION : RECURRENTINTRODUCTION Description: When a woman has had two consecutive or three total first-trimester spontaneous pregnancy losses it is considered recurrent abortion. Prevalence: Found in 0.4% to 0.8% of women. Predominant Age: Reproductive.Genetics: No genetic pattern. ETIOLOGY AND PATHOGENESIS Causes: Chromosomal abnormalities. When the losses occur early in gestation, there is a greater likelihood that a chromosomal abnormality is the cause, whereas for later abortions a maternal cause such as a uterine anomaly is more likely. Although most chromosomal abnormali- ties result from disorders of meiosis in gamete formation or in mitosis after fertilization, 5% of couples who expe- rience recurrent abortion have a detectable parental chromosomal abnormality, surgically correctable uterine abnormalities, an incompetent cervix, or intrauterine synechiae. Uterine anomalies are found in 15% to 25% of women with recurrent abortion. The possibility of immunologic factors as a cause of recurrent losses should also be evaluated (e.g., lupus anticoagulant). Two thirds of recurrent abortions occur after 12 weeks of gestation, suggesting that maternal or environmental factors play a large role in this process. Risk Factors: Those associated with spontaneous abor- tion, including increasing maternal and paternal age and autoimmune disorders. CLINICAL CHARACTERISTICS Signs and Symptoms Two consecutive or three total first-trimester spontane- ous pregnancy losses. DIAGNOSTIC APPROACH Differential Diagnosis Uterine anomalies (fibroids, incompetent cervix, intra- uterine synechiae, developmental abnormalities such as a septum or duplication) Chromosomal abnormality (maternal [more likely] or paternal) Immunologic causes (such as lupus anticoagulant) Endocrinopathy (such as hypothyroidism) Coagulopathy or thrombophilia Associated Conditions: None. Workup and Evaluation Laboratory: Screening for immunologic or endocrine abnormality; coagulopathy or thrombophilia as indicated. Imaging: Ultrasonography of the pelvis or hysterosalpin- gography may be of assistance when a uterine anomaly is suspected. Special Tests: Karyotyping of both parents is recom- mended when recurrent early abortions have occurred. Karyotyping of the abortus may be helpful but requires 396 fresh tissue, specialized transport media, and laboratory capabilities.Diagnostic Procedures: Hysteroscopy may be of limited value (indicated only when a uterine factor is strongly considered). Pathologic Findings None. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Support and evaluation.Specific Measures: Those with parental chromosomal anomalies may be offered donor oocytes or artificial insemination with donor sperm. Uterine anomalies or submucous fibroids may be treated, although care must be taken to recognize the possibility of continued failure for other reasons and the possible impact of future deliv- ery options.Diet: No specific dietary changes indicated.Activity: No restriction.Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP100 (Repeated Miscarriage), AP090 (Early Pregnancy Loss: Miscarriage, Ectopic Pregnancy, and Molar Pregnancy). Drug(s) of Choice None. Progesterone and thyroid supplements have not been shown to reduce the risk of pregnancy loss. When immunologic factors are present, the use of low-dose aspirin and subcutaneous heparin (5000 units twice daily) has reduced the rate of subsequent loss. FOLLOW-UP Patient Monitoring: Normal health maintenance. Prevention/Avoidance: None.Expected Outcome: Based on underlying pathologic condition.

AMENORRHEA : PRIMARYINTRODUCTION Description: Primary amenorrhea is the absence of normal menstruation in a patient without previously established cycles. Prevalence: Uncommon.Predominant Age: Mid to late teens.Genetics: One third caused by chromosomal abnormali- ties such as 45,XO, 46,XY gonadal dysgenesis, or 46,XX q5 X long-arm deletion. ETIOLOGY AND PATHOGENESIS Causes: Gonadal abnormalities (failure, 60% of patients) autoimmune ovarian failure (Blizzard syndrome), gonadal dysgenesis, pure gonadal dysgenesis, 45,XO (Turners syndrome), 46,XY gonadal dysgenesis (Swyer syndrome), 46,XX q5 X chromosome long-arm dele- tion, mixed or mosaic, follicular depletion, autoimmune disease, infection (e.g., mumps), infiltrative disease processes (e.g., tuberculosis, galactosemia), iatrogenic ovarian failure (e.g., alkylating chemotherapy, irradia- tion), ovarian insensitivity syndrome (resistant ovary [Savages] syndrome), 17-hydroxylase deficiency, chronic anovulation of pubertal onset. Extragonadal anomalies (40%)congenital absence of uterus and vagina (15%) (Mullerian agenesis), constitutional delay, imperforate hymen, male pseudohermaphroditism (tes- ticular feminization syndrome), pituitaryhypothalamic dysfunction, transverse vaginal septum. Risk Factors: None known. CLINICAL CHARACTERISTICS Signs and Symptoms No period by age 14 with no secondary sex changes No period by age 16 regardless of secondary sex changes No period by 2 years after the start of secondary sex changes Evaluation should not be delayed any time there is the suggestion of a chromosomal abnormality or an obstructed genital tract. DIAGNOSTIC APPROACH Differential Diagnosis Pregnancy before first cycle Obstructed outflow tract (making menstruation cryptic) Gonadal dysgenesis Uterine agenesis Androgen insensitivity syndrome Mayer-Rokitansky-Kuster-Hauser syndrome Associated Conditions: Infertility, abnormal stature (short or tall), and cardiac changes in some congenital syndromes; hypertension and hypokalemic alkalosis in 17-hydroxylase deficiency, virilization, or hirsutism; and cyclic pelvic pain with outflow obstruction. Renal and skeletal abnormalities may also occur. Prolonged amenorrhea is associated with an increased risk of osteoporosis. Workup and Evaluation Laboratory: The development of sexual hair or breasts provides an outward sign of androgen and estrogen pro- duction, respectively. Imaging: Based on conditions being considered.Special Tests: Based on conditions being considered. Diagnostic Procedures: Laparoscopy to evaluate internal organs and gonads may be required. Pathologic Findings None. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Determination of underlying cause(s). Specific Measures: Based on the diagnosis and specific needs of the patient. Diet: No specific dietary changes indicated.Activity: No restriction.Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP049 (Menstruation [Especially for Teens]) or AP041 (Growing Up [Especially for Teens]). Drug(s) of Choice Based on underlying cause. Hormone replacement may be required or desirable for many patients. FOLLOW-UP Patient Monitoring: Normal health maintenance. Prevention/Avoidance: None.Possible Complications: Risk of gonadal malignancy is increased if a Y chromosome is present. Risk of osteo- porosis is present if the patient is hypoestrogenic and does not receive replacement therapy. Extensive damage to the upper tract may occur if obstruction is not corrected. Expected Outcome: Menstruation and fertility may be restored for many of these patients if there are no struc- tural or chromosomal conditions that preclude the possibility (uterine agenesis, androgen insensitivity syn- drome, gonadal dysgenesis).

AMENORRHEA : SECONDARYINTRODUCTION Description: Secondary amenorrhea is the absence of normal menstruation in a patient with previously estab- lished cycles. Prevalence: Common.Predominant Age: Reproductive (menarche to menopause).Genetics: No genetic pattern. ETIOLOGY AND PATHOGENESIS Causes: Most commonpregnancy. Other causesend organ: Ashermans syndrome, outflow obstruction; ovarian: menopause, resistant ovary [Savages] syndrome, toxin exposure, surgery, autoimmune disease; central, behavioral, and others: anorexia, obesity, athletics (over- training), drugs/medications, nutritional deprivation, psychogenic (stress); medical: adenoma, craniopharyn- gioma, Sheehans syndrome, tuberculosis, sarcoid, empty sella syndrome; virilizing syndromes: polycystic ovary syndrome, adrenal hyperplasia, virilizing tumors. Risk Factors: Unprotected intercourse, exposure to toxins or radiation, surgery, overtraining, eating disorders, psychosocial stress. CLINICAL CHARACTERISTICS Signs and Symptoms Absent menstruationmay be associated with symp- toms that suggest the cause. DIAGNOSTIC APPROACH Differential Diagnosis Pregnancy Menopause (natural or premature) Exogenous hormone use Virilization Metabolically active ovarian tumor Lactational amenorrheaAssociated Conditions: Endometrial hyperplasia, osteo- porosis in hypoestrogenic states. Workup and Evaluation Laboratory: A pregnancy test is always indicated. Imaging: Based on conditions being considered.Special Tests: Women who are younger than age 30 who have ovarian failure should have a karyotype performed.Diagnostic Procedures: Based on conditions being considered. Pathologic Findings None. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Determination of underlying cause(s). If a pathologic condition has been ruled out and preg- 400 nancy is not desired, reassurance only. Evaluation should not be delayed any time there is the suggestion of an abnormality or pregnancy. Specific Measures: Periodic (every 3 to 6 months) pro- gestin withdrawal to prevent endometrial hyperplasia and to re-evaluate status. Specific therapy is based on the underlying cause (such as estrogen/progestin therapy for menopause). Treatment is focused on restoring or inducing ovulation if pregnancy is desired. Diet: No specific dietary changes indicated.Activity: No restriction.Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP049 (Menstruation [Especially for Teens]) or AP041 (Growing Up [Especially for Teens]), AP121 (Polycystic Ovary Syndrome), AP047 (The Menopause Years). Drug(s) of Choice Based on diagnosis (e.g., thyroid replacement for hypothy- roidism, estrogen and progestin therapy for ovarian failure, periodic progestin therapy [oral or transvaginal] or ovulation induction for anovulation). Contraindications: All medical interventions are contra- indicated until pregnancy has been ruled out. FOLLOW-UP Patient Monitoring: Normal health maintenance. Watch for changing status or intercurrent pregnancy. Prevention/Avoidance: None (contraception).Possible Complications: Endometrial hyperplasia with continued estrogen (unopposed) exposure.Expected Outcome: Most causes of secondary amenor- rhea may be successfully treated with return of menstruation.

ANOVULATIONINTRODUCTION Description: Anovulation is characterized by absence of ovulation in women of reproductive age. Prevalence: Up to 30% of couples who are infertile. Predominant Age: Reproductive.Genetics: No genetic pattern, some chromosomal abnor- malities are associated with premature ovarian failure (deletions on the X chromosome). ETIOLOGY AND PATHOGENESIS Causes: Physiologicmenopause (normal or premature), pregnancy; hormonalelevated prolactin, hypothyroid- ism; functionalexercise (excessive), malnutrition, obesity, weight loss; drug-inducedalkylating chemo- therapy, hormonal contraception, marijuana, tranquil- izers; neoplasiacraniopharyngioma, hypothalamic hamartoma, pituitary adenoma (prolactin-secreting), small cell carcinoma of lung; psychogenicanorexia nervosa, anxiety, pseudocyesis, stress; otheradrenal androgenization, central nervous system trauma, chronic medical illness, hemochromatosis, histiocytosis X, inter- nal carotid artery aneurysms, irradiation, juvenile diabe- tes mellitus, polycystic ovary syndrome, Sheehans syndrome (postpartum ischemic necrosis), syphilitic gummas, tuberculosis, uremia. Risk Factors: Factors noted in previous section. CLINICAL CHARACTERISTICS Signs and Symptoms Amenorrhea (primary or secondary)Absence of premenstrual molimina (prodromal symptoms) DIAGNOSTIC APPROACH Differential Diagnosis Pregnancy must always be considered Menopause Congenital abnormality of the outflow tract causing amenorrhea Cervical stenosis resulting in amenorrheaAssociated Conditions: Infertility, dysfunctional uterine bleeding, endometrial hyperplasia, and endometrial cancer. Workup and Evaluation Laboratory: Follicle-stimulating hormone (FSH), prolac- tin, thyroid function studies (e.g., sensitive thyroid- stimulating hormone [TSH]), others as indicated clinically. Imaging: No imaging indicated.Special Tests: Basal body temperature charting may be used to detect ovulation, but other laboratory tests are more specific for establishing the cause.Diagnostic Procedures: Endometrial biopsy performed during the presumed luteal phase. Pathologic Findings Endometrialproliferative changes only, hyperplasia pos- sible with prolonged anovulation. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Evaluation.Specific Measures: If pregnancy is desired, induction of ovulation. If pregnancy is not desired, periodic progestin therapy.Diet: No specific dietary changes indicated.Activity: No restriction.Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP136 (Evaluating Infertility), AP137 (Treat- ing Infertility), AP095 (Abnormal Uterine Bleeding), AP121 (Polycystic Ovary Syndrome), AP047 (The Menopause Years). Drug(s) of Choice Ovulation inductionclomiphene citrate 50 mg PO daily on days 5 to 10 of the menstrual cycle, may be increased to 100 mg PO daily on days 5 to 10 of the menstrual cycle if ovulation does not occur. Metformin (1500 mg/ day) as an adjunctive treatment for ovulation induction (considered now as first-line therapy for polycystic ovary syndrome). Progestin withdrawalmedroxyprogesterone acetate 5 to 10 mg for 1 to 14 days each month. Contraindications: Undiagnosed amenorrhea or bleeding. Precautions: Progestins should not be used until preg- nancy has been ruled out. Alternative Drugs Aromatase inhibitors are efficacious as primary agents for ovulation induction (e.g., letrozole; 2.5mg or 5mg administered for 5 days, beginning on cycle days 3 to 5.). Norethindrone acetate 5 to 10 mg for 10 to 14 days each month for progestin withdrawal. FOLLOW-UP Patient Monitoring: Normal health maintenance. Prevention/Avoidance: None.Possible Complications: Infertility, dysfunctional uterine bleeding, endometrial hyperplasia.Expected Outcome: For many patients, normal ovulation and fertility may be restored.

INFERTILITYINTRODUCTION Description: Infertility is the inability to conceive or bear a child despite more than 1 year of trying. Under ordi- nary circumstances, 80% to 90% of normal couples con- ceive during 1 year of attempting pregnancy. Infertility may be further subdivided into primary and secondary types based on the patients past reproductive history: patients who are infertile and nulligravid are in the primary infertility group and those who have become pregnant more than 1 year previously, regardless of the outcome of that pregnancy, are in the secondary infertil- ity group. Slightly more than one half of patients expe- riencing infertility fall into the primary group. Prevalence: Eight percent to eighteen percent of the American population; slightly higher for couples who have never conceived and slightly lower for couples who have conceived before. Roughly 6.1 million women in the United States. Predominant Age: Reproductive. The prevalence of infertility increases with the age of the woman. Age- related infertility is becoming more common because about 20% of American women delay their attempts at pregnancy to after age 35. Genetics: No specific genetic pattern. Some chromosomal abnormalities are associated with reduced or absent fertility. ETIOLOGY AND PATHOGENESIS Causes: Approximately 35% to 50% of infertility is due to a male factor such as azoospermia. Female factors, such as tubal disease (20% to 30%), ovulation disorders (10% to 15%), and cervical factors (5%), contribute to the roughly 50% to 60% of female causes. The remain- ing 10% to 20% of couples have no identifiable cause for their infertility (idiopathic). Couples experiencing primary infertility are more likely to have idiopathic or chromosomal causes than are couples who have con- ceived previously. Risk Factors: Factors that increase the risk of anovulation (obesity, athletic overtraining, exposure to drugs or toxins), pelvic adhesive disease (infection, surgery, endo- metriosis), impaired sperm production (mumps, varico- cele), or sperm delivery (ejaculatory dysfunction). CLINICAL CHARACTERISTICS Signs and Symptoms Inability to conceive after 1 year of attempts. DIAGNOSTIC APPROACH Differential Diagnosis Recurrent pregnancy loss Primary infertilitychromosomal abnormality (e.g., 45,XO [Turners syndrome], 46,XY gonadal dysgenesis [Swyer syndrome], 46,XX q5 X chromosome long-arm deletion) Congenital abnormality of the genital tract (either partner) Associated Conditions: Based on the pathologic condi- tion causing the infertility. Workup and Evaluation Laboratory: Based on diagnoses being considered. Imaging: Based on diagnoses being considered.Special Tests: Half of all women found to have tubal factor infertility have no history of antecedent infections or surgery, supporting the need to evaluate tubal patency in patients regardless of their past history. Diagnostic Procedures: Based on diagnoses being considered. Pathologic Findings None. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Supportbecause infertility involves both members of the couple and intrudes on the most intimate aspects of their relationship, all with no promise of success, a great deal of support is vital. Specific Measures: The treatment of a couple experienc- ing infertility is based on identifying the impediment to fertility and overcoming or bypassing it to achieve pregnancy. Most couples can be successfully treated with conventional therapies (e.g., medications or surgery) rather than advanced assisted reproductive technologies. In vitro fertilization techniques account for only about 5% of infertility services and are associ- ated with a roughly 32% live delivery rate per egg retrieval (2004). Diet: No specific dietary changes indicated.Activity: No restriction, unless athletic activities are thought to be adversely affecting fertility (exercise- induced amenorrhea). While the evaluation of infertility proceeds, couples should be instructed to continue attempting pregnancy through intercourse timed to the most fertile days of the cycle.Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP136 (Evaluating Infertility), AP137 (Treat- ing Infertility). Drug(s) of Choice (Based on diagnosis of cause.)Secondary infertility (ovulation induction)clomiphene citrate 50 mg PO daily on days 5 to 10 of the menstrual cycle; may be increased to 100 mg PO daily on days 5 to 10 of the menstrual cycle if ovulation does not occur. Metformin (1500 mg/day) as an adjunctive treatment for ovulation induction (considered now as first-line therapy for polycystic ovary syndrome).Contraindications: Undiagnosed infertility. Precautions: The possibility of ovarian hyperstimulation must be considered and close follow-up should be main- tained if ovulation induction is attempted. Alternative Drugs Gonadotropin-releasing hormone (GnRH) agonists may be used to control the hormonal environment during ovulation induction. Human gonadotropins may be used to induce ovulation but are associated with an increased risk of multiple ovulations and multiple gestations if pregnancy ensues. FOLLOW-UP Patient Monitoring: Normal health maintenance. Prevention/Avoidance: None.Expected Outcome: Less than 40% of couples with primary infertility conceive after 6 years of therapy com- pared with more than 50% of secondary infertility couples who conceive by 3 years.

MENOPAUSEINTRODUCTION Description: Menopause is an endocrinopathy caused by the loss of normal ovarian steroidogenesis because of age, chemotherapy, radiation, or surgical therapy. (An endocrinopathy is the loss of an endocrine function with adverse health consequences.) Prevalence: Of postmenopausal women who do not receive estrogen replacement, 100%. Predominant Age: Median 51.5, 95% between 44 and 55 (or after surgical menopause). Genetics: Loss of genetic material from the long arm of the X chromosome is associated with premature menopause. ETIOLOGY AND PATHOGENESIS Causes: Loss of estrogen production because of surgery, chemotherapy (alkylating agents), radiation, or natural cessation of ovarian function (menopause). Risk Factors: Menopause may occur at a younger age in smokers, those with poor nutrition or chronic illness, or those who have a loss of genetic material from the long arm of the X chromosome. CLINICAL CHARACTERISTICS Signs and Symptoms Absence of menstruation (with a normal uterus and outflow tract) Hot flashes, flushes, and night sweats Vaginal atrophy Dysuria, urgency, and urgency incontinence; urinary frequency; nocturia; and an increased incidence of stress urinary incontinence Decrease in libido Irregular bleeding common during the climacteric (perimenopausal) period DIAGNOSTIC APPROACH Differential Diagnosis Pregnancy Hypothyroidism Polycystic ovary syndrome Prolactin-secreting tumor Hypothalamic dysfunction HypothyroidismAssociated Conditions: Dyspareunia, vulvodynia, atro- phic vulvitis, osteoporosis, increased risk of cardiovascu- lar disease, hot flashes and flushes, sleep disturbances, stress urinary incontinence, and others. WORKUP AND EVALUATION Laboratory: Usually not necessary. When the diagnosis of ovarian failure must be confirmed, measurement of serum follicle-stimulating hormone (FSH) is sufficient. Levels of greater than 100 mIU/mL are diagnostic, 424 although lower levels (40 to 50 mIU/mL) may be suffi- cient to establish a diagnosis when symptoms are also present. Serum estradiol levels may be determined (generally less than 15 pg/mL) but are less reliable as a marker of ovarian failure. A pregnancy test is always indicated in women who are perimenopausal and sexually active and not using contraception. Imaging: No imaging indicated. Standard imaging does not document bone loss of less than 30%. Special Tests: A vaginal maturation index may be obtained but is generally not required for diagnosis. Bone densi- tometry may be indicated for those at special risk. When noncyclic bleeding occurs in these patients, endometrial biopsy should be strongly considered. Women younger than age 30 years who have ovarian failure should have a karyotype performed. Pathologic Findings Vaginal, vulvar, and endometrial atrophy. Thinned ovarian stroma with few, inactive oocytes. Accelerated calcium loss from bone. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Health maintenance, annual mam- mogram, annual pelvic and rectal examinations, thyroid and cholesterol screening every 5 years or as indicated, tetanus booster shot every 10 years, pneumococcus vaccine as indicated. Specific Measures: For symptom relief: systemic estrogen (estrogen/progestin) therapy. (Less than 1% of women do not benefit from therapy.) Topical estrogen supplements. Diet: Adequate dietary calcium (1000 to 1500 mg/day). Activity: No restriction, weightbearing activity to promote bone health, cardiovascular fitness training/maintenance. Patient Education: Reassurance; American College of Obstetricians and Gynecologists Patient Education Pamphlet AP047 (The Menopause Years), AP066 (Hormone Replacement Therapy), AP158 (Herbal Products for Menopause), AP048 (Preventing Osteopo- rosis), AP028 (Vaginitis: Causes and Treatments). Drug(s) of Choice (Most common drug doses shown.)Oral estrogensconjugated equine estrogens (0.625 to 1.25mg/day), diethylstilbestrol, esterified estrogens (0.625 to 1.25 mg/day), ethinyl estradiol (0.05 mg/day), micronized estradiol (0.5 to 1mg/day), piperazine estrone sulfate, estropipate, quinestrol. Injectable estrogensconjugated equine estrogens, estra- diol benzoate, estradiol cypionate, estradiol valerate (oil), estrone (aqueous), ethinyl estradiol, polyestradiol phosphate. Topical estrogens17-estradiol (transdermal) (0.05 to 0.10 mg/day), conjugated equine estrogens (0.625 mg/ g), estradiol (0.1 mg/g), estropipate (1.5 mg/g).

Contraindications: Systemic therapy: active liver disease, carcinoma of the breast (current), chronic liver damage (impaired function), endometrial carcinoma (current), recent thrombosis (with or without emboli), unexplained vaginal bleeding. Relative contraindications/special considerationsendometriosis, familial hyperlipidemia, gallbladder disease, hypertension (uncontrolled), migraine headaches, seizure disorders, thrombophlebitis (unknown risk), uterine leiomyomas. Topical use known sensitivity to vehicle. Precautions: Continuous estrogen exposure without peri- odic or concomitant progestins increases the risk of endometrial carcinoma 6-fold to 8-fold. Continuous estrogen/progestin therapy frequently results in random vaginal bleeding, but biopsy or other investigation is still warranted. Patients receiving cyclic estrogen/progestin therapy should experience vaginal bleeding only after withdrawal of the progestin; biopsy or other investiga- tion is warranted for other bleeding. Interactions: Raloxifene should not be used with chole- styramine. Most therapies alter the effects of warfarin therapy. Alternative Drugs Raloxifene (Evista) 60 mg PO dailyno relief for hot flashes or vaginal dryness, but does reduce breast cancer risk. Progestin therapy (oral, vaginal, or injectable)effective for hot flashes, may reduce bone loss, but has no effect on coronary artery disease or urogenital atrophy. Clonidine (oral or transdermal).Bellergal-S (phenobarbital, ergotamine tartrate, belladonna).Alendronate (Fosamax)for osteoporosis.Topical moisturizers for atrophic vaginitis.(Botanical agents have not been shown to be efficacious for most menopausal symptoms or for osteoporosis prevention.) FOLLOW-UP Patient Monitoring: Normal health maintenance. Serious consideration should be given to a trial of therapy dis- continuation after 2 or more years. Prevention/Avoidance: Estrogen replacement therapy at menopause. The use of progestins is required if the patient retains her uterus to reduce the risk of iatrogenic endometrial hyperplasia or cancer. Therapy may be oral (such as medroxyprogesterone acetate [Provera] 5 to 10 mg PO daily for 12 to 14 days per month or 2.5 mg PO daily) or vaginal (progesterone bioadhesive gel [Crinone] 4% to 8%, 45 mg [1.125 g] intravaginally every other day for six doses per month). Possible Complications: Endometrial hyperplasia if the uterus is present and progestins not used, vaginal bleed- ing (predictable or otherwise). Expected Outcome: Reversal of symptoms, re- establishment of normal physiology with treatment. Selective estrogen receptor modulators (also called SERMS or tissue-specific estrogens) may provide pro- tection against cardiac, bone, and colon cancer and Alzheimers disease with reduced rates of risk for both breast and endometrial cancer.

POLYCYSTIC OVARY SYNDROMEINTRODUCTION Description: Polycystic ovary syndrome (PCOS) consists of amenorrhea, hirsutism, insulin resistance, and obesity in association with enlarged, multicystic ovaries. Prevalence: Up to 5% of women, 30% of secondary amenorrhea. The most common hormonal disorder among women of reproductive age. Predominant Age: Begins at menarche.Genetics: No genetic pattern established, suggestion of increased family tendency. ETIOLOGY AND PATHOGENESIS Causes: The exact pathophysiology of polycystic ovary syndrome is not well established, but increased ampli- tude of gonadotropin-releasing hormone (GnRH) pul- sation and abnormal secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during puberty are thought to result in androgen excess. Ele- vated levels of LH persist and may be used to help establish the diagnosis. Insulin resistance is a prominent aspect of this syndrome. Risk Factors: Borderline adrenal hyperplasia, occult hypothyroidism, and childhood obesity. CLINICAL CHARACTERISTICS Signs and Symptoms Anovulation and amenorrhea (75% to 80%) Infertility (75%) Excessive hair growth, primarily along the angle of the jaw, upper lip, and chin (70%) Obesity (50%) (apple-shaped obesity centered around the lower half of the torso) Acanthosis nigricans Acne DIAGNOSTIC APPROACH Differential Diagnosis Virilization (especially when hirsutism is in a male pattern) Familial hypertrichosis Cushings disease (truncal obesity, facial rounding, cervicodorsal fat deposition [buffalo hump], and red or purple striae are often not fully developed)Associated Conditions: Increased risk of cardiovascular disease (adverse lipid profiles), diabetes (insulin resis- tance in 50% of patients), hypertension, and infertility. Workup and Evaluation Laboratory: Elevated levels of luteinizing hormone may be used to help establish the diagnosis. (A two-to-one ratio of luteinizing hormone to follicle-stimulating hormone is considered diagnostic.) Evaluation for pos- sible virilizing process (prolactin, follicle-stimulating hormone, thyroid screening). (Patients suspected of having adrenal sources of hyperandrogenicity may be screened by measuring 24-hour urinary-free cortisol, by performing adrenocorticotropin hormone [ACTH] 428 stimulation tests, or an overnight dexamethasone sup- pression test.) Serum testosterone (total) is generally 70 to 120 ng/mL and androstenedione is 3 to 5 ng/mL. Dehydroepiandrosterone sulfate (DHEA-s) is elevated in approximately 50% of patients. Imaging: Ultrasonography (abdominal or transvaginal) may identify ovarian enlargement or the presence of multiple small follicles. Magnetic resonance imaging (MRI) or computed tomography (CT) may be used to evaluate the adrenal glands. Special Tests: None indicated.Diagnostic Procedures: History, physical examination, imaging and laboratory evaluations. May be confirmed at laparoscopy, but seldom required for diagnosis. Pathologic Findings The ovaries are enlarged with a thickened white capsule. They contain multiple follicles in varying stages of devel- opment. Luteinization of theca cells may be present. MANAGEMENT AND THERAPY Nonpharmacologic General Measures: Evaluation. Weight loss is often asso- ciated with resolution of symptoms and a return of men- strual function in patients with mild or early polycystic ovary syndrome. Specific Measures: Medical therapy has replaced surgical treatment. Treatment depends on desire for pregnancy; if pregnancy is desired, then ovulation induction may be required. Diet: No specific dietary changes indicated; weight loss or control desirable. Activity: No restriction.Patient Education: American College of Obstetricians and Gynecologists Patient Education Pamphlet AP121 (Polycystic Ovary Syndrome). Drug(s) of Choice Combination oral contraceptives (less than 50-mg formu- lation and a progestin other than norgestrel). If DHEA-s is elevated, dexamethasone (0.25 to 0.5 mg PO every bedtime) may be added to oral contraceptives. Spironolactone (100 to 200 mg PO daily).Metformin (1500 mg/day) as an adjunctive treatment for ovulation induction (considered now as first-line therapy for polycystic ovary syndrome).Contraindications: Pregnancy. (Spironolactone is a cate- gory X drug; patients using it and able to become preg- nant must use reliable contraception.) Alternative Drugs Gonadotropin-releasing hormone analogues and clomi- phene citrate may be used. FOLLOW-UP Patient Monitoring: Normal health maintenance once diagnosis and management have been implemented. There is an increased risk of diabetes in patients with polycystic ovaries. Weight control and contraception should also be addressed.Prevention/Avoidance: Role of normalized weight debated.Possible Complications: Chronic anovulation is associ- ated with osteoporosis and endometrial hyperplasia or carcinoma.Expected Outcome: Generally good response to medical therapy.

TURNERS SYNDROMEINTRODUCTION Description: Caused by the absence of one X chromo- some, Turners syndrome is a collection of stigmata that includes edema of the hands and feet, webbing of the neck, short stature, left-sided heart or aortic anomalies, and gonadal dysgenesis resulting in primary amenorrhea and infertility. These patients have normal mental abilities but may have difficulty with mathematics, visualmotor coordination, and spatialtemporal processing. Prevalence: One of 2700 female births.Predominant Age: Present at birth, may not be detected until puberty is delayed.Genetics: Sporadic, loss of one X chromosome (45,XO, 60% of cases, others partial losses: amenorrhea with long-arm loss; short stature with short-arm loss). Of conceptuses with only one X chromosome, 98% spon- taneously abort in early pregnancy. ETIOLOGY AND PATHOGENESIS Causes: Monosomy for the X chromosome.Risk Factors: Translocations involving the X chromo- some (rare). CLINICAL CHARACTERISTICS Signs and Symptoms Short stature (