Hyperandrogenism: Symptoms, Types, Causes and Treatment

Hyperandrogenism is a common but often misunderstood endocrine disorder, especially in women of reproductive age. Defined by excess levels of androgens (“male” hormones like testosterone) in the body, hyperandrogenism can affect physical appearance, reproductive health, and even metabolic function. Understanding its symptoms, types, underlying causes, and available treatments is essential for patients and healthcare professionals alike.

Symptoms of Hyperandrogenism

Hyperandrogenism doesn't present the same way in everyone. Its symptoms can range from subtle skin changes to striking physical transformations, often impacting self-esteem, reproductive health, and overall well-being. Recognizing these signs early is crucial for effective management and prevention of long-term complications.

Symptom	Description	Typical Patients	Source(s)
Hirsutism	Excessive hair growth in male-like patterns	Women/adolescents	2 4 5 6 10
Acne	Persistent or severe acne	Adolescents/adults	2 4 5 10
Androgenic Alopecia	Hair thinning, typically at the crown	Women	2 4 10 15
Menstrual Irregularity	Irregular or absent periods	Reproductive-age women	3 4 5 7
Virilization	Deepened voice, increased muscle mass	Rare, severe cases	2 4
Acanthosis Nigricans	Dark, velvety skin patches	Often with obesity/insulin resistance	9 10
Infertility	Difficulty conceiving	Adults	1 3

Table 1: Key Symptoms

Cutaneous and Hair Changes

• Hirsutism is the most common and visible sign, defined by excessive growth of coarse hair in areas where women typically have minimal or no hair, such as the chin, upper lip, chest, and back. It affects up to 80% of hyperandrogenic women and is often scored using standardized systems like the modified Ferriman-Gallwey scale 2 5 6.
• Acne—especially severe, persistent, or treatment-resistant varieties—often arises due to increased sebum production from androgen stimulation of the skin's sebaceous glands 2 4 10.
• Androgenic alopecia (hair thinning at the crown or temples) is another distressing manifestation, sometimes appearing without other symptoms 2 4 10 15.

Menstrual and Reproductive Symptoms

• Menstrual irregularity is a frequent complaint, particularly in women with polycystic ovary syndrome (PCOS), manifesting as oligomenorrhea (infrequent periods) or amenorrhea (absence of periods). This is a direct result of disrupted ovarian function due to excess androgens 3 4 5 7.
• Infertility can result from chronic anovulation, where ovulation fails to occur regularly, making conception difficult 1 3.

Metabolic and Other Features

• Acanthosis nigricans is a telltale sign of insulin resistance, seen as dark, velvety skin patches in body folds. It often coexists with hyperandrogenism, especially in women with PCOS or HAIR-AN (HyperAndrogenism, Insulin Resistance, and Acanthosis Nigricans) syndrome 9 10.
• Virilization, including deepening of the voice, increased muscle mass, and clitoral enlargement, is rare and typically signals a severe androgen excess, often from tumors 2 4.

Types of Hyperandrogenism

Hyperandrogenism is not a single disease but a spectrum of disorders with varied origins and clinical presentations. Understanding the main types helps target diagnosis and treatment.

Type	Source of Androgen Excess	Typical Features	Source(s)
Ovarian (e.g., PCOS)	Ovaries	Hirsutism, acne, obesity, irregular menses	3 4 6 7 9
Adrenal	Adrenal glands	Early puberty, advanced bone age, acne	1 4 7
Peripheral	Increased tissue sensitivity	Isolated skin/hair changes	7 8 10
Tumor-related	Ovarian or adrenal tumors	Rapid virilization, severe symptoms	2 4 7 11
Gestational	Pregnancy-related sources	Maternal and fetal effects	11
Idiopathic/Physiologic	No identifiable cause	Mild symptoms, normal labs	5 7

Table 2: Types of Hyperandrogenism

Ovarian Hyperandrogenism

• Polycystic Ovary Syndrome (PCOS) is the most prevalent cause, accounting for the majority of cases in women. PCOS is characterized by a combination of hyperandrogenism, irregular periods, and polycystic ovarian morphology on ultrasound. It can present with obesity, insulin resistance, and increased cardiovascular risk 3 6 7 9.
• Functional ovarian hyperandrogenism is a variant where only the ovarian source is implicated, often in adolescents 4 14.

Adrenal Hyperandrogenism

• Nonclassical Congenital Adrenal Hyperplasia (NC21OHD) is the most frequent adrenal cause. Here, a partial enzyme deficiency leads to mild excess production of adrenal androgens. Symptoms may include early puberty, hirsutism, acne, and infertility 1 4 7.
• Adrenal tumors are rare but may present with sudden, severe symptoms and virilization 2 4 7 11.

Peripheral and Idiopathic Forms

• Peripheral hyperandrogenism involves increased skin sensitivity to normal androgen levels, often due to upregulated local 5α-reductase activity. This can result in pronounced skin and hair changes without elevated blood androgen levels 7 8 10.
• Idiopathic/Physiologic hyperandrogenism is diagnosed when all other causes are excluded, and symptoms are mild, often overlapping with normal puberty 5 7.

Tumor-Related and Gestational Hyperandrogenism

• Androgen-secreting tumors (ovarian or adrenal) are rare but dangerous, often causing rapid-onset severe symptoms such as deepening of the voice and muscle hypertrophy 2 4 7 11.
• Gestational hyperandrogenism occurs during pregnancy, sometimes due to rare conditions like luteoma or placental enzyme defects, with potential effects on both mother and fetus 11.

Causes of Hyperandrogenism

Pinpointing the cause is essential for effective management. While some cases are genetic or developmental, others are linked to metabolic or environmental factors.

Cause	Mechanism or Contributing Factor	Associated Type(s)	Source(s)
PCOS	Ovarian steroidogenesis, insulin resistance	Ovarian	3 6 9
Congenital Adrenal Hyperplasia (CAH)	Enzyme deficiencies (21-hydroxylase)	Adrenal	1 7
Insulin Resistance	Stimulates ovarian androgen production	PCOS, HAIR-AN	3 9 12
Tumors	Androgen-secreting ovarian/adrenal tumors	Tumor-related	2 4 7 11
Pregnancy-Related	Luteoma, aromatase deficiency, fetal CAH	Gestational	11
Increased 5α-Reductase Activity	Enhanced conversion to DHT in skin	Peripheral	8 10
Idiopathic	Unknown or multifactorial	Idiopathic/physiologic	5 7

Table 3: Causes of Hyperandrogenism

Polycystic Ovary Syndrome (PCOS)

PCOS remains the most common cause of hyperandrogenism, responsible for up to 90% of cases in women. It is driven by both ovarian overproduction of androgens and metabolic disturbances like insulin resistance. Insulin resistance not only aggravates androgen production but also contributes to a cycle of obesity and worsening hyperandrogenism 3 6 9 12.

Congenital Adrenal Hyperplasia (CAH)

Nonclassical 21-hydroxylase deficiency (NC21OHD) is a genetic disorder leading to mild overproduction of adrenal androgens. It is common in certain populations and can be underdiagnosed due to its subtle presentation 1 7.

Insulin Resistance and Metabolic Factors

Insulin resistance is central to many hyperandrogenic states, especially in PCOS and HAIR-AN syndrome. High insulin levels stimulate the ovaries to produce more androgens and can impair insulin action further, perpetuating a vicious cycle 3 9 12.

Tumors and Rare Causes

Rapid-onset, severe hyperandrogenism, particularly with virilization, should raise suspicion for androgen-secreting tumors. Pregnancy can unmask or induce hyperandrogenism through unique mechanisms, with potential risks for the developing fetus 2 4 7 11.

Peripheral and Idiopathic Mechanisms

In some, increased local conversion of testosterone to the more potent dihydrotestosterone (DHT) in the skin leads to symptoms, even if blood androgen levels are normal. These cases often have pronounced skin/hair changes 8 10.

Treatment of Hyperandrogenism

Managing hyperandrogenism is highly individualized, targeting both the underlying cause and the patient's most distressing symptoms. Treatments may be medical, lifestyle-based, or, in rare cases, surgical.

Treatment	Purpose/Target Symptom	Typical Patient(s)	Source(s)
Combined Oral Contraceptives (COCs)	Lower androgen levels, regulate periods	Most reproductive-age women	4 10 16
Antiandrogens (spironolactone, flutamide, cyproterone)	Block androgen effects	Hirsutism, acne, alopecia	4 12 14 15 16
Insulin Sensitizers (metformin)	Improve insulin resistance, decrease androgens	PCOS, HAIR-AN	3 12 13 16
Glucocorticoids	Suppress adrenal androgen production	CAH, adrenal causes	1 4
Lifestyle Modification	Weight loss, improve metabolic profile	Obese/overweight patients	3 10 16
Surgery	Remove androgen-secreting tumor	Tumor-related cases	2 4 7

Table 4: Treatment Options

Medical Therapy

• Combined Oral Contraceptives (COCs): These are first-line for many women, helping regulate menstrual cycles and reduce androgen levels. They are particularly effective for hirsutism and acne 4 10 16.
• Antiandrogens: Medications such as spironolactone, flutamide, and cyproterone acetate block the action of androgens at target tissues. They are used for hirsutism, acne, and sometimes androgenic alopecia. Flutamide is noted to be effective for hair loss, while others like cyproterone may be less so 4 12 14 15 16.
• Insulin Sensitizers (Metformin, Pioglitazone): Especially beneficial in PCOS, these drugs improve insulin sensitivity, indirectly lowering androgen levels and improving metabolic profiles 3 12 13 16.
• Glucocorticoids: Low-dose steroids like dexamethasone can suppress adrenal androgen production in congenital adrenal hyperplasia (CAH), reversing symptoms 1 4.
• Estrogen Replacement: In postmenopausal women with hyperandrogenism and insulin resistance, estrogen therapy can reduce androgenicity and improve metabolic outcomes 13.

Lifestyle Interventions

• Weight loss and physical activity are strongly recommended, particularly for overweight or obese women. Even moderate weight loss can improve symptoms and metabolic health 3 10 16.

Surgical and Other Specific Therapies

• Surgery: Reserved for rare cases of androgen-secreting tumors, with the goal of removing the source of excess hormones 2 4 7.
• Tailored Dermatologic Treatment: For skin manifestations like acne and hirsutism, topical therapies or cosmetic procedures may be considered alongside medical treatment 4 10.

Treatment Considerations

• Personalization: Treatment choice depends on the underlying cause, severity of symptoms, reproductive goals, and patient preference. Symptom distress and impact on quality of life must be considered before initiating therapy 5.
• Expectations Management: Improvement, especially for hair symptoms, may take months. Anticipatory guidance and patient education are crucial for adherence and satisfaction 5 16.

Conclusion

Hyperandrogenism is a multifaceted syndrome with significant implications for physical, reproductive, and metabolic health. Early recognition, accurate diagnosis, and individualized management are key to improving outcomes for affected individuals.

Key Takeaways:

• Hyperandrogenism manifests most commonly as hirsutism, acne, androgenic alopecia, and menstrual irregularity, with rarer severe features like virilization 2 4 5 6 10.
• The most prevalent types are ovarian (notably PCOS), adrenal (e.g., NC21OHD), and peripheral/idiopathic forms, with rare tumor-related and gestational variants 1 3 4 6 7 9 11.
• Causes include PCOS, congenital adrenal hyperplasia, insulin resistance, tumors, increased skin 5α-reductase activity, and in some cases, unknown factors 1 3 7 8 9.
• Treatment is tailored to the underlying cause and patient’s needs, with options including hormonal contraceptives, antiandrogens, insulin sensitizers, glucocorticoids, lifestyle changes, and surgery for tumors 1 4 10 12 14 15 16.
• Ongoing monitoring and a holistic, patient-centered approach are essential for optimal care and quality of life.

Understanding and addressing hyperandrogenism can profoundly impact the health, confidence, and happiness of those affected. If you or someone you know is experiencing symptoms, consult a healthcare provider for evaluation and personalized care.