Gynecology Topic 45. Virilism and hirsutism

I. Definitions and Etiology

Definitions

• Virilism / virilization: Development of male sex characteristics in a woman due to marked androgen excess.
• Hirsutism: Androgen-dependent excessive terminal hair growth in a male pattern.
• Key distinction: Hirsutism can be mild/chronic; virilization or rapid progression suggests severe androgen excess, especially tumor.
• 5-alpha-reductase converts testosterone to dihydrotestosterone (DHT), a more potent androgen.

Etiology

• PCOS: Most common cause of hirsutism; chronic hirsutism + acne + oligomenorrhea/amenorrhea ± obesity/insulin resistance.
• Ovarian androgen-secreting tumor: Sertoli-Leydig cell tumor, Leydig cell tumor, ovarian hyperthecosis.
• Adrenal causes: Congenital adrenal hyperplasia (usually nonclassic 21-hydroxylase deficiency), adrenal tumor, Cushing syndrome.
• Iatrogenic/drugs: Anabolic steroids, testosterone, danazol, some progestins.
• Idiopathic/familial hirsutism: Regular cycles, normal androgen levels, increased follicle sensitivity.

II. Clinical Features

Hirsutism and Virilization

• Hirsutism: Coarse dark terminal hair on upper lip/chin, chest, linea alba, lower abdomen, back or inner thighs.
• Acne, oily skin, androgenic alopecia / temporal balding.
• Menstrual dysfunction: Oligomenorrhea, amenorrhea, anovulation → infertility.
• Virilization signs:

• Severe hirsutism.
• Deepening voice.
• Clitoromegaly.
• Breast atrophy.
• Increased muscle bulk.
• Libido changes.

Red Flags for Tumor

• Rapid onset or rapid progression over months.
• Any virilization, especially voice deepening or clitoromegaly.
• Very high testosterone or DHEAS.
• Palpable pelvic/abdominal mass.
• Onset after menopause.
• Cushingoid features: Central obesity, moon face, purple striae, hypertension, proximal muscle weakness.

III. Diagnosis

History and Examination

• History: Age at onset, speed of progression, menstrual pattern, fertility, weight gain, acne/alopecia, medication or anabolic steroid exposure.
• Physical examination: BMI, blood pressure, Ferriman-Gallwey score, acne/acanthosis/striae/alopecia, clitoromegaly, pelvic or abdominal mass.
• Pregnancy test when amenorrhea or delayed menses is possible.

Laboratory Tests

• Total testosterone ± free testosterone: Ovarian androgen excess marker; increased in PCOS, Sertoli-Leydig tumor or ovarian hyperthecosis.
• DHEAS: Adrenal androgen marker; increased in CAH, adrenal tumors and some Cushing cases.
• 17-hydroxyprogesterone: Morning serum test for CAH; ACTH stimulation if borderline/positive.
• LH/FSH: Increased LH/FSH ratio may support PCOS classically, but is not required for diagnosis.
• Dexamethasone suppression test, late-night salivary cortisol or urinary free cortisol when Cushing syndrome is suspected.
• TSH/prolactin if menstrual disturbance, galactorrhea or endocrine symptoms suggest another cause.

Interpretation and Imaging

• High testosterone + normal DHEAS → Ovarian source likely.
• High DHEAS ± high testosterone → Adrenal source likely.
• Marked testosterone elevation, especially >150-200 ng/dL depending on lab/context → Suspect androgen-secreting tumor.
• Marked DHEAS elevation, especially >700 mcg/dL depending on lab/context → Suspect adrenal tumor.
• Pelvic US/CT/MRI: Ovarian tumor or PCOS morphology.
• Adrenal CT/MRI: Markedly elevated DHEAS, adrenal-pattern labs or Cushing/adrenal mass suspicion.

IV. Treatment

Lifestyle and Medical Treatment

• Weight reduction in overweight PCOS: Improves insulin resistance, ovulation and androgen levels.
• Combined OCP: First-line if pregnancy not desired; suppresses LH-dependent ovarian androgen production and increases SHBG → decreased free testosterone.
• Antiandrogens: Use only with reliable contraception because of fetal risk.

• Spironolactone: Androgen receptor blockade.
• Finasteride: 5-alpha-reductase inhibitor → decreased DHT formation.

• Metformin: Useful for insulin resistance/metabolic features in PCOS; not primary hirsutism therapy.
• Glucocorticoids: Classic CAH and selected nonclassic CAH cases.
• Cosmetic treatment: Shaving, waxing, laser/photoepilation, electrolysis; response to endocrine therapy is slow, usually months.

Surgical / Cause-Specific Treatment

• Ovarian androgen-secreting tumor: Surgical resection.
• Adrenal tumor: Adrenalectomy after endocrine evaluation.
• Cushing syndrome or prolactinoma: Treat the endocrine cause.
• PCOS infertility: Weight optimization + ovulation induction; ovarian drilling only in selected resistant PCOS cases.