2.8 Ovarian, Testicular & Reproductive Endocrine Disorders

1. Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive-age women and the most commonly tested item in this subsection. The Rotterdam criteria require two of three features:

1. Oligo- or anovulation (cycles longer than 35 days or fewer than eight per year)
2. Clinical or biochemical hyperandrogenism (hirsutism, acne, androgenic alopecia, or elevated free testosterone)
3. Polycystic ovarian morphology on ultrasound

The examination trap is that PCOS is a diagnosis of exclusion. Before applying the criteria you must exclude:

Rapidly progressive virilization — clitoromegaly, voice deepening, male-pattern balding over months — is not PCOS. It signals an androgen-secreting ovarian or adrenal tumor and requires imaging.

Management by patient goal

• Not seeking pregnancy: combined hormonal contraception is first line, treating menstrual irregularity, hirsutism and acne simultaneously while providing endometrial protection.
• Seeking pregnancy: letrozole is the preferred first-line ovulation induction agent, having surpassed clomiphene for live-birth rate in this population.
• Metabolic risk: weight reduction improves ovulatory function; metformin addresses insulin resistance and glucose intolerance but is not a primary fertility agent.
• Endometrial protection is mandatory. Chronic anovulation exposes the endometrium to unopposed estrogen, raising endometrial hyperplasia and carcinoma risk. A woman with PCOS who has gone many months without a withdrawal bleed needs cyclic progestin or continuous contraception.

2. Premature Ovarian Insufficiency

Cessation of ovarian function before age 40, defined by amenorrhea with elevated follicle-stimulating hormone on two occasions and low estradiol. Distinguish it from hypothalamic amenorrhea, in which gonadotropins are low or normal.

Evaluation includes karyotype (Turner syndrome and mosaicism), FMR1 premutation testing (fragile X carriers), and screening for autoimmune adrenal insufficiency and thyroid disease. Systemic estrogen with a progestin is offered until the average age of natural menopause to protect bone and cardiovascular health — this is replacement of a physiologic deficit, not the same risk calculus as postmenopausal hormone therapy in an older woman.

3. Amenorrhea: A Working Sequence

1. Exclude pregnancy. Always the first test.
2. Measure thyroid-stimulating hormone and prolactin.
3. Measure follicle-stimulating hormone to separate ovarian failure (high) from hypothalamic-pituitary causes (low or normal).
4. Assess for hyperandrogenism if hirsutism or virilization is present.

Functional hypothalamic amenorrhea — from low energy availability, excessive exercise or psychological stress — produces low gonadotropins with low estradiol and is a recognized cause of premature bone loss.

4. Male Hypogonadism

Testosterone deficiency requires both symptoms and confirmed low levels. Symptoms include reduced libido, erectile dysfunction, reduced morning erections, loss of body hair, gynecomastia, reduced muscle mass and low mood.

Testing rules that generate exam points:

• Draw testosterone in the early morning (levels have a marked diurnal rhythm) and in the fasting state.
• Confirm a low value on a second morning sample before diagnosing.
• Do not test during acute illness, which transiently suppresses the axis.
• If sex hormone-binding globulin is likely to be abnormal — obesity, diabetes, advanced age, hepatic or thyroid disease — measure free testosterone.

Then localize with luteinizing hormone (LH) and follicle-stimulating hormone (FSH):

Secondary hypogonadism mandates prolactin measurement and pituitary imaging, because a prolactinoma or other sellar mass may be the cause. Opioid-induced androgen deficiency is common and frequently overlooked.

Testosterone therapy: contraindications and monitoring

Testosterone is contraindicated in men desiring fertility — exogenous testosterone suppresses gonadotropins and therefore spermatogenesis, and is a cause of male infertility rather than a treatment for it. Other contraindications include untreated obstructive sleep apnea, an elevated hematocrit, and known prostate or breast cancer. Monitoring includes hematocrit (erythrocytosis is the most common adverse effect) and prostate-specific antigen in age-appropriate men.

5. Male Infertility

Evaluation begins with semen analysis, repeated if abnormal. Azoospermia is separated by FSH:

• High FSH — primary testicular failure.
• Normal or low FSH with normal testicular volume — consider obstruction, including congenital bilateral absence of the vas deferens, which warrants cystic fibrosis transmembrane conductance regulator testing.

Varicocele is the most common surgically correctable cause. Exogenous anabolic steroid use is a common and reversible cause that must be asked about directly.

6. Erectile Dysfunction

Erectile dysfunction is enumerated in this blueprint subsection and is frequently a sentinel marker of endothelial dysfunction, often preceding a coronary event by several years. New erectile dysfunction warrants cardiovascular risk assessment.

• Preserved nocturnal and morning erections suggest a psychogenic contribution.
• Gradual loss of all erections suggests a vascular, neurogenic or endocrine cause.
• Review medications: thiazides, beta-blockers, selective serotonin reuptake inhibitors, antiandrogens.
• Phosphodiesterase-5 inhibitors are absolutely contraindicated with nitrates in any form, because the combination causes profound hypotension.

7. Gynecomastia

True gynecomastia is glandular tissue — a firm, concentric, often tender subareolar disc — and must be distinguished from lipomastia (fatty tissue without a discrete disc) and from male breast cancer (hard, eccentric, fixed, possibly with nipple retraction or discharge; unilateral).

It reflects a rise in the estrogen-to-androgen ratio. Causes to consider:

• Physiologic: puberty, aging
• Drugs: spironolactone, cimetidine, ketoconazole, antiretrovirals, antipsychotics, anabolic steroids, marijuana, alcohol
• Cirrhosis (impaired estrogen clearance) and chronic kidney disease
• Hypogonadism of either type; hyperthyroidism
• Tumors: human chorionic gonadotropin-secreting germ cell tumors, adrenal or Leydig cell tumors

Rapid-onset gynecomastia in a young man should prompt testicular examination and measurement of human chorionic gonadotropin, because a testicular germ cell tumor is the diagnosis not to miss. Drug withdrawal and treatment of the underlying cause are first line; longstanding fibrotic gynecomastia does not regress medically.