HIRSUTISM — A COMPREHENSIVE REVIEW

 

HIRSUTISM — A COMPREHENSIVE REVIEW

Introduction

Hirsutism is a clinical condition characterized by excessive, male-pattern hair growth in women. The term specifically refers to the growth of terminal (coarse, pigmented) hair in androgen-dependent areas such as the face, chest, back, lower abdomen, and thighs. This growth pattern is a result of increased androgen action, whether due to elevated circulating androgen levels, increased sensitivity of hair follicles to normal androgen concentrations, or both.

While body and facial hair are natural in all women, hirsutism becomes clinically significant when the distribution and thickness resemble that typically seen in males. Importantly, hirsutism is not merely a cosmetic issue—it can be a manifestation of underlying endocrine disorders, sometimes with serious health implications. In many cases, however, it is benign but psychologically distressing, impacting self-esteem, social interactions, and quality of life.

The global prevalence of hirsutism varies between 5–15% of women, depending on the population studied, the criteria used, and ethnic background. Understanding the complex physiology of hair growth, the hormonal regulation involved, and the pathophysiological mechanisms underlying hirsutism is essential for accurate diagnosis and management.

Normal Hair Growth Physiology

To appreciate hirsutism, it is necessary to understand how hair normally develops and is regulated.

Types of Hair:

1. Lanugo Hair – Soft, fine hair covering the fetus; normally shed before birth.
2. Vellus Hair – Short, fine, non-pigmented hair found on most of the body.
3. Terminal Hair – Coarse, pigmented hair found on the scalp, eyebrows, eyelashes, and—after puberty—in androgen-dependent areas.

Hair Growth Cycle:

• Anagen (Growth Phase) – Lasts years for scalp hair, months for body hair.
• Catagen (Transition Phase) – Short phase of follicle regression.
• Telogen (Resting Phase) – Hair is eventually shed.

In androgen-dependent sites, hair follicles can convert vellus hair to terminal hair when stimulated by androgens. This conversion is the core mechanism behind hirsutism.

Hormonal Control of Hair Growth

Androgens—primarily testosterone and its more potent derivative, dihydrotestosterone (DHT)—are the major regulators of terminal hair growth in certain areas.

Key hormonal influences:

• Testosterone – Produced by the ovaries and adrenal glands.
• DHT – Formed from testosterone by the enzyme 5-alpha-reductase in hair follicles; more potent at the androgen receptor.
• Dehydroepiandrosterone sulfate (DHEAS) – Secreted by the adrenal glands; can be converted to testosterone.
• Androstenedione – Produced by both ovaries and adrenal glands.

Hair follicles in different body regions have varying densities of androgen receptors and 5-alpha-reductase activity, explaining why some areas (upper lip, chin, chest) are particularly androgen-sensitive.

Definition of Hirsutism

Hirsutism is defined as excess terminal hair growth in women in a male-pattern distribution. It must be distinguished from:

• Hypertrichosis – Generalized excessive hair growth not limited to androgen-dependent sites; unrelated to androgen excess.
• Virilization – More severe androgen effects such as deepening of voice, clitoromegaly, male-pattern baldness, and increased muscle mass.

Assessment and Scoring

The Ferriman–Gallwey score is the most widely used clinical tool to grade hirsutism. It evaluates nine androgen-sensitive body sites, each scored from 0 (no hair) to 4 (extensive terminal hair). A score above 8 (in Caucasian women) is generally considered diagnostic, though thresholds vary by ethnicity.

Etiology of Hirsutism

Hirsutism can arise from various causes, broadly classified into:

1. Polycystic Ovary Syndrome (PCOS)

• Accounts for 70–80% of hirsutism cases.
• Characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology.
• Pathophysiology: Increased ovarian androgen production, often linked to insulin resistance.

2. Idiopathic Hirsutism

• Normal androgen levels and regular ovulatory cycles.
• Likely due to increased peripheral 5-alpha-reductase activity or heightened androgen receptor sensitivity.

3. Non-classical Congenital Adrenal Hyperplasia (NCAH)

• Mild enzyme defects (usually 21-hydroxylase deficiency).
• Presents with hirsutism, acne, menstrual irregularity.

4. Androgen-Secreting Tumors

• Rare, but important to detect early.
• Rapid onset and progression of hirsutism with virilization.
• Tumors may arise from ovaries or adrenal glands.

5. Cushing’s Syndrome

• Excess cortisol production, often with concomitant androgen excess.
• Associated with central obesity, striae, hypertension, glucose intolerance.

6. Medications

• Androgenic progestins, danazol, anabolic steroids, minoxidil, cyclosporine, phenytoin.

7. Other Endocrine Disorders

• Hypothyroidism, hyperprolactinemia, acromegaly.

Pathophysiology of Hirsutism

Hirsutism is the manifestation of excessive terminal hair growth in women, distributed in a pattern typically seen in males, such as on the face, chest, lower abdomen, upper back, and thighs. The underlying mechanism involves increased androgen action at the level of the hair follicle, which can be due to elevated circulating androgens, increased local conversion of weak androgens to potent ones, or heightened sensitivity of hair follicles to androgens.

Understanding the pathophysiology of hirsutism requires an appreciation of normal hair biology, hormonal regulation, and the interplay between systemic and local factors.

1. Hair Follicle Biology and Androgen Dependence

Hair follicles are specialized skin structures capable of producing hair fibers throughout life. The type of hair produced depends on the size and activity of the follicle, as well as hormonal influences.

Types of Hair:

• Vellus Hair: Short, fine, lightly pigmented; covers most of the body before puberty.
• Terminal Hair: Long, coarse, pigmented; found on scalp, eyebrows, eyelashes, and—after puberty—on androgen-dependent areas.

In hirsutism, vellus hairs in androgen-sensitive areas (e.g., upper lip, chin, chest, abdomen) transform into terminal hairs under the influence of androgens.

2. The Hair Growth Cycle and Hormonal Influence

Hair grows in three main phases:

1. Anagen (Growth phase): Longest phase; duration varies by site.
2. Catagen (Regression phase): Short transitional phase.
3. Telogen (Resting phase): Ends with shedding.

Androgens influence both anagen duration and follicle diameter in specific areas, leading to thicker, darker, and longer hairs.

3. Role of Androgens in Hair Growth

Androgens are the key hormonal regulators in hirsutism. They:

• Stimulate conversion of vellus hair to terminal hair in androgen-sensitive areas.
• Increase hair shaft thickness and pigmentation.
• Prolong the anagen phase in certain body areas.

Major Androgens Involved:

• Testosterone – Derived from ovarian and adrenal sources.
• Dihydrotestosterone (DHT) – More potent; formed from testosterone via 5-alpha-reductase in the skin and hair follicles.
• Androstenedione – Precursor from ovaries and adrenals.
• Dehydroepiandrosterone sulfate (DHEAS) – Predominantly adrenal in origin; can be converted to testosterone.

4. Sources of Androgens

Ovaries:

• Produce testosterone and androstenedione.
• In conditions such as polycystic ovary syndrome (PCOS), increased luteinizing hormone (LH) secretion stimulates ovarian theca cells to produce more androgens.

Adrenal Glands:

• Secrete DHEAS and androstenedione.
• In disorders like congenital adrenal hyperplasia (CAH) or Cushing’s syndrome, adrenal androgen production is elevated.

Peripheral Conversion:

• Androgens can be produced locally in the skin from circulating precursors, amplifying androgen action at the follicle.

5. Mechanisms Leading to Hirsutism

A. Increased Circulating Androgen Levels

This is the most straightforward mechanism:

• PCOS: Increased LH:FSH ratio → ovarian theca cell hyperactivity → elevated testosterone.
• Non-classical congenital adrenal hyperplasia (NCAH): Enzyme defects (often 21-hydroxylase deficiency) → accumulation of androgen precursors.
• Androgen-secreting tumors: Rare; cause very high testosterone or DHEAS levels with rapid hair growth and virilization.

B. Increased Free Testosterone

Even if total testosterone is normal, low levels of sex hormone-binding globulin (SHBG) can increase the free, biologically active fraction.

• Hyperinsulinemia (common in PCOS) suppresses SHBG synthesis in the liver, raising free testosterone.
• Obesity also lowers SHBG.

C. Increased Peripheral Conversion of Androgens

In the skin, the enzyme 5-alpha-reductase converts testosterone to DHT, which binds androgen receptors with greater affinity and potency. Increased activity of this enzyme can occur locally, even with normal systemic androgen levels.

D. Increased Androgen Receptor Sensitivity

Some women have normal androgen levels but more sensitive androgen receptors in hair follicles, possibly due to genetic variations in receptor structure or co-regulatory proteins. This explains idiopathic hirsutism—normal hormones but excessive hair growth.

6. Molecular Pathways in the Hair Follicle

Hair follicles contain:

• Androgen receptors (AR) in dermal papilla cells.
• 5-alpha-reductase (types I and II), converting testosterone to DHT.
• Aromatase, which can convert androgens to estrogens (counteracting effect).

Pathophysiological sequence:

1. Circulating testosterone enters the follicle.
2. Locally converted to DHT by 5-alpha-reductase.
3. DHT binds AR in dermal papilla cells.
4. AR–DHT complex influences gene transcription → stimulates follicular keratinocyte proliferation, increases melanogenesis, and enlarges the follicle.
5. Vellus hair transforms to terminal hair.

7. Interaction with Other Hormonal Systems

Insulin and IGF-1:

• High insulin levels (from insulin resistance) enhance ovarian androgen production and lower SHBG.
• Insulin-like growth factor-1 (IGF-1) may act synergistically with androgens at the follicular level.

Cortisol:

• In Cushing’s syndrome, adrenal overproduction of both glucocorticoids and androgens leads to hirsutism.

Prolactin:

• Hyperprolactinemia can disrupt gonadotropin secretion and promote adrenal androgen synthesis.

8. Examples of Pathophysiology in Common Causes

Polycystic Ovary Syndrome (PCOS)

• Hypersecretion of LH and insulin resistance → increased ovarian androgen production.
• Reduced SHBG → more free testosterone.
• Elevated peripheral 5-alpha-reductase activity.

Idiopathic Hirsutism

• Normal androgen levels.
• Increased follicular 5-alpha-reductase or heightened AR sensitivity.

Non-classical Congenital Adrenal Hyperplasia

• Deficient 21-hydroxylase → accumulation of 17-hydroxyprogesterone → shunted into androgen pathway.

Androgen-Secreting Tumors

• Massive androgen production overwhelms normal control mechanisms, causing rapid, severe hirsutism with virilization.

9. Ethnic and Genetic Influences

Ethnicity plays a role in baseline hair growth and androgen sensitivity. Women of Mediterranean, Middle Eastern, and South Asian descent often have higher baseline terminal hair density than East Asian women. Genetic variations in AR and 5-alpha-reductase genes may influence susceptibility.

10. Summary Flow of Pathophysiology

1. Trigger – Elevated androgens (ovarian/adrenal/peripheral) or increased follicular sensitivity.
2. Circulation – Testosterone and precursors circulate bound to SHBG (inactive) or free (active).
3. Local Activation – In follicle, 5-alpha-reductase converts testosterone → DHT.
4. Receptor Binding – DHT binds androgen receptor → nuclear signaling.
5. Follicular Changes – Enlargement, increased pigment, longer anagen → terminal hair growth.
6. Clinical Outcome – Coarse, pigmented hair in androgen-dependent distribution.

Clinical Presentation

Symptoms:

• Gradual onset of coarse hair growth in face, chin, chest, abdomen, back.
• Menstrual irregularities in many cases.
• Acne, seborrhea, scalp hair thinning (androgenetic alopecia).

Signs of Virilization (suggest severe androgen excess):

• Voice deepening
• Clitoromegaly
• Increased muscle mass
• Breast atrophy
• Marked temporal hair recession

Diagnostic Evaluation

A systematic approach includes:

1. History

• Age of onset, progression rate.
• Menstrual history.
• Family history of hirsutism or endocrine disorders.
• Drug use.

2. Physical Examination

• Distribution and density of hair.
• Signs of virilization.
• Signs of endocrine disorders (acanthosis nigricans, obesity, Cushingoid features).

3. Laboratory Tests

• Serum total and free testosterone.
• DHEAS.
• LH and FSH.
• 17-hydroxyprogesterone (for NCAH).
• Cortisol levels if Cushing’s suspected.
• Prolactin, thyroid function tests as indicated.

4. Imaging

• Pelvic ultrasound for PCOS or ovarian tumors.
• CT or MRI for adrenal pathology.

Management

Management aims to treat underlying cause, reduce hair growth, and address cosmetic concerns.

Lifestyle Measures

• Weight reduction in obese patients (especially PCOS).
• Improves insulin sensitivity and lowers androgen levels.

Pharmacological Treatments

1. Oral Contraceptives

   • First-line in many women with PCOS.
   • Reduce LH secretion, increase SHBG, lower free testosterone.

2. Anti-androgens

   • Spironolactone – Blocks androgen receptors, inhibits 5-alpha-reductase.
   • Finasteride – Inhibits type II 5-alpha-reductase.
   • Flutamide – Potent androgen receptor blocker (hepatotoxicity limits use).

3. Insulin-Sensitizing Agents

   • Metformin – Improves insulin resistance in PCOS, modest effect on hirsutism.

4. Topical Treatments

   • Eflornithine cream – Slows facial hair growth.

Mechanical/Cosmetic Methods

• Shaving, plucking, waxing.
• Depilatory creams.
• Laser hair removal and intense pulsed light (IPL) – Provide longer-lasting results.

Prognosis

The response to treatment is gradual—because hair follicles already in anagen phase will continue to grow until the cycle completes. Noticeable improvement may take 6–12 months. Prognosis depends on cause:

• Idiopathic hirsutism and mild PCOS respond well to medical therapy.
• Tumor-related hirsutism resolves rapidly after removal.
• Chronic conditions require ongoing management.

Psychosocial Impact

Hirsutism significantly affects mental health:

• Reduced self-confidence.
• Social withdrawal.
• Higher rates of anxiety and depression.
• Body image disturbances.

Addressing the emotional component is essential; counseling and support groups may be beneficial.

Prevention of Hirsutism

Preventing hirsutism involves addressing the underlying hormonal imbalances, metabolic disturbances, and lifestyle factors that contribute to excessive androgen activity. While some causes—such as genetic predisposition, ethnicity, or certain endocrine disorders—cannot be entirely prevented, many risk factors can be minimized through proactive health measures. Prevention focuses on early detection, hormonal regulation, metabolic health, and avoiding triggers that promote androgen excess.

General Health and Lifestyle Measures

• Maintaining a healthy body weight reduces insulin resistance, lowers circulating insulin levels, and helps prevent excessive ovarian androgen production. Even modest weight loss of 5–10% in overweight women can significantly reduce hirsutism risk, particularly in those prone to polycystic ovary syndrome (PCOS).
• Regular physical activity improves insulin sensitivity, increases energy expenditure, and helps regulate menstrual cycles. Aerobic exercise combined with strength training supports hormonal balance and prevents the cascade of events leading to excess hair growth.
• A balanced diet rich in whole grains, vegetables, lean protein, and healthy fats supports metabolic stability. Reducing intake of refined carbohydrates and sugars helps control insulin levels, indirectly lowering androgen production.
• Avoidance of crash diets or extreme caloric restriction is important, as these can disrupt normal hormonal rhythms and ovulatory cycles, potentially contributing to hirsutism in susceptible individuals.
• Managing stress through relaxation techniques, yoga, meditation, or mindfulness can help regulate cortisol levels. Chronic stress can alter adrenal function and increase androgen production.

Preventing Hormonal Triggers

• Early identification and management of menstrual irregularities can prevent progression to sustained hyperandrogenism. Seeking medical evaluation for delayed menarche, prolonged cycles, or amenorrhea ensures prompt intervention.
• Monitoring ovulatory function in reproductive-age women is useful, particularly in those with risk factors for PCOS. Addressing anovulation early can prevent the long-term hormonal environment that promotes hirsutism.
• Hormonal contraceptives, when used appropriately under medical guidance, can help regulate menstrual cycles and suppress excessive ovarian androgen production. Choosing estrogen-containing combined oral contraceptives increases sex hormone–binding globulin (SHBG), lowering free testosterone levels.
• Avoiding misuse of androgen-containing medications or supplements is crucial. Certain anabolic steroids, testosterone creams, or androgenic progestins can directly trigger hirsutism.
• Women undergoing treatment with drugs known to cause hair growth, such as danazol, cyclosporine, or minoxidil, should discuss alternatives with their physician if at risk for hirsutism.

Addressing Metabolic and Endocrine Disorders

• Early screening for insulin resistance, particularly in women with a family history of type 2 diabetes or PCOS, allows for timely intervention before hyperinsulinemia stimulates androgen overproduction.
• Management of metabolic syndrome through lifestyle measures or medical therapy reduces the hormonal drive toward hirsutism. This includes controlling hypertension, improving lipid profiles, and preventing central obesity.
• Prompt diagnosis and treatment of endocrine disorders such as hypothyroidism, hyperprolactinemia, and Cushing’s syndrome can prevent secondary hyperandrogenism.
• For women with a strong family history of congenital adrenal hyperplasia, genetic counseling and early biochemical screening can allow for preventative strategies before symptoms develop.

Preventing Progression in At-Risk Groups

• Adolescent girls with early signs of androgen excess—such as acne, irregular cycles, or early hair growth in androgen-sensitive areas—benefit from early medical assessment. Intervening during this stage can prevent progression to more pronounced hirsutism.
• In women with PCOS, maintaining consistent follow-up with healthcare providers ensures timely adjustments in treatment, preventing worsening hair growth over time.
• For women with idiopathic hirsutism, ongoing dermatological and endocrinological monitoring can help detect subtle increases in hair density or distribution early, allowing for quicker treatment adjustments.

Role of Insulin Sensitivity in Prevention

• Because hyperinsulinemia plays a major role in stimulating ovarian androgen production, improving insulin sensitivity is one of the most effective preventive approaches.
• Consuming low-glycemic-index foods helps maintain stable blood sugar and insulin levels, reducing hormonal stimulation of hair follicles.
• Engaging in daily moderate-intensity physical activity—such as brisk walking, cycling, or swimming—can significantly improve insulin responsiveness.
• In selected cases with high metabolic risk, insulin-sensitizing drugs like metformin, under medical supervision, can help prevent progression of hirsutism by reducing ovarian androgen output.

Skin and Hair Follicle–Level Prevention

• Protecting skin from chronic inflammation or irritation may indirectly reduce hair follicle activation in some women.
• Using skincare regimens that prevent severe acne or folliculitis can help avoid local inflammatory triggers that may increase androgen activity at the skin level.
• For women with mild early hair growth, topical eflornithine cream can be considered under medical advice to slow hair follicle activity before extensive terminal hair develops.

Avoiding External Androgen Exposure

• Being cautious with certain cosmetics, herbal preparations, or over-the-counter supplements that may contain hidden androgenic ingredients can prevent accidental androgen exposure.
• Avoiding second-hand exposure to topical testosterone products used by male partners, as contact transfer can cause localized hirsutism in women.
• Reading ingredient labels carefully when purchasing hormonal skin treatments or “anti-aging” products marketed online, as some may contain androgenic substances without clear labeling.

Reproductive Health and Family Planning Considerations

• Women planning pregnancy who have PCOS or a history of hormonal imbalance benefit from preconception counseling. Stabilizing hormonal profiles before pregnancy can help reduce the risk of worsening hirsutism in the postpartum period.
• Timely treatment of menstrual irregularities after childbirth or menopause can prevent the onset of late-onset hirsutism, especially in women with underlying metabolic risks.
• Postmenopausal women experiencing hair pattern changes should undergo hormonal evaluation promptly, as early detection of androgen excess can prevent further hair development.

Psychological Support and Early Cosmetic Intervention

• Addressing the psychological impact of early hair growth can motivate women to seek medical help sooner, leading to earlier preventive treatment.
• Early adoption of safe cosmetic hair removal techniques—such as laser hair removal or intense pulsed light therapy—can prevent hair follicles from becoming permanently thicker and more resistant to treatment.
• Avoiding repeated aggressive plucking or waxing in the same area can help prevent irritation-induced follicular stimulation that sometimes worsens hair growth.

Public Health and Educational Approaches

• Raising awareness among young women about the signs of hyperandrogenism and encouraging early consultation with healthcare providers can promote timely prevention.
• Educating women on the connection between weight, insulin resistance, and androgen production empowers them to make lifestyle choices that reduce hirsutism risk.
• Providing culturally sensitive information in communities where hirsutism is stigmatized helps break barriers to early medical evaluation.

Long-Term Prevention Strategies

• For women with chronic conditions like PCOS, combining lifestyle measures with periodic medical therapy (such as low-dose oral contraceptives or anti-androgens) can maintain androgen control and prevent new hair growth.
• Monitoring hormonal levels regularly allows for prompt adjustments to therapy, preventing flare-ups of hair growth.
• Ensuring balanced nutrition, adequate sleep, and avoidance of hormonal disruptors in the environment supports endocrine stability over time.

Recent Advances

• Development of selective androgen receptor modulators (SARMs) for targeted therapy.
• More effective long-pulse lasers with better safety profiles for darker skin types.
• Genetic studies identifying polymorphisms linked to increased androgen receptor sensitivity.

Conclusion

Hirsutism is a common but often under-recognized condition that can serve as a marker for underlying endocrine abnormalities. A careful, individualized approach—balancing medical, cosmetic, and psychological interventions—can significantly improve outcomes. Early diagnosis and appropriate management not only restore physical appearance but also enhance emotional well-being.

The interplay between hormones, genetic predisposition, and environmental factors makes hirsutism a fascinating yet challenging clinical entity. Continued research promises more precise and effective therapies in the future.