What causes hirsutism in women of reproductive age?

What Causes Hirsutism in Women

Polycystic ovary syndrome (PCOS) is the most common cause of hirsutism, accounting for 70-80% of cases in women of reproductive age, characterized by hyperandrogenic chronic anovulation with accelerated pulsatile GnRH secretion, insulin resistance, and hyperinsulinemia leading to ovarian androgen overproduction. 1

Primary Causes by Frequency

Most Common: PCOS (70-80% of cases)

• PCOS affects 4-6% of women in the general population and represents the overwhelming majority of hirsutism cases 1
• The pathophysiology involves hypersecretion of luteinizing hormone, ovarian theca stromal cell hyperactivity, and FSH-granulosa cell axis hypofunction, resulting in hyperandrogenism, follicular arrest, and ovarian acyclicity 2
• Clinical features include menstrual irregularity (oligomenorrhea or amenorrhea), acne, obesity, and elevated testosterone or LH levels 2
• Insulin resistance and hyperinsulinemia drive downstream metabolic dysregulation that perpetuates androgen excess 2

Idiopathic Hirsutism (5-15% of cases)

• Women with idiopathic hirsutism have normal ovulatory function and normal androgen levels despite terminal hair growth in male-pattern distribution 3
• This represents a diagnosis of exclusion after ruling out PCOS and other endocrine disorders 3, 4
• Strong familial predilection exists due to genetic factors regulating androgen receptor activity and 5α-reductase activity in hair follicles 3

Non-Classic Congenital Adrenal Hyperplasia (1-10% depending on ethnicity)

• 21-hydroxylase deficiency is the most common form 1, 5
• Prevalence varies significantly by ethnicity, with higher rates in certain populations 5
• Diagnosed by elevated 17-hydroxyprogesterone levels 1

Rare but Critical Causes to Exclude

Androgen-secreting tumors (ovarian or adrenal):

• Total testosterone >200 ng/dL strongly suggests an androgen-secreting tumor and requires urgent imaging 1, 4
• These tumors present with rapid-onset virilization over weeks to months, often with clitoromegaly, deepening voice, and severe hirsutism 1, 6
• DHEAS >600 μg/dL indicates adrenal source and raises concern for adrenocortical carcinoma 6

Medication-induced hirsutism:

• Exogenous androgens and certain antiepileptic drugs (particularly valproate) can trigger or worsen hirsutism 2, 1
• Older antiepileptic drugs (carbamazepine, phenobarbital, phenytoin) induce hepatic cytochrome P450-dependent steroid hormone breakdown and SHBG production, altering free testosterone levels 2

Other endocrine disorders:

• Cushing's syndrome presents with truncal obesity, striae, and hypertension alongside hirsutism 1, 4
• Hyperprolactinemia causes oligomenorrhea, amenorrhea, galactorrhea, and hirsutism 2
• Acromegaly rarely presents with hirsutism 5

Pathophysiological Mechanism

The development of hirsutism requires both elevated androgens and increased hair follicle sensitivity to androgens 5, 7:

• Circulating testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase within susceptible hair follicles 7
• DHT is the potent androgen directly responsible for terminal hair growth stimulation 7
• Tissue androgen receptor content, 5α-reductase activity, and other enzyme activities (3α- and 17β-hydroxysteroid dehydrogenase, ornithine decarboxylase) determine individual susceptibility 5

Special Population Considerations

Women with epilepsy:

• PCOS prevalence is 10-25% in women with temporal lobe epilepsy, even without antiepileptic drug exposure, compared to 4-6% in the general population 2, 1
• Hypothalamic amenorrhea affects 12% of women with temporal lobe epilepsy versus 1.5% of the general population, though this typically presents without hyperandrogenism 2, 6

Ethnic variations:

• Hirsutism may be less prevalent among women of Asian extraction despite androgen excess 3
• Non-classic congenital adrenal hyperplasia prevalence varies significantly by ethnicity 5

Critical Clinical Pitfalls

Do not confuse isolated polycystic ovaries with PCOS:

• Isolated polycystic ovaries (>10 peripheral cysts 2-8 mm diameter on ultrasound) occur in 17-22% of women without symptoms 2
• PCOS diagnosis requires clinical/biochemical hyperandrogenism AND ovulatory dysfunction, not just ultrasound findings 1, 6

Avoid androgenic progestins in oral contraceptives:

• OCPs containing norethisterone derivatives or levonorgestrel can worsen hirsutism 1
• Select formulations with non-androgenic or anti-androgenic progestins for treatment 1

Weight gain as a trigger:

• Weight gain and obesity directly trigger PCOS development in susceptible women through insulin resistance mechanisms 2
• Even 5% weight reduction improves metabolic and reproductive abnormalities in obese women with PCOS 1