Androgens are steroid hormones, including testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA), naturally present in all individuals. They are primarily produced in the adrenal glands and the gonads (ovaries in females and testes in males). Androgens regulate various bodily functions, such as bone density, muscle mass development, and sexual function.
While essential, an abnormal elevation of these hormones in women, known as hyperandrogenism, disrupts the body’s balance. This hormonal excess leads to noticeable physical changes and metabolic disturbances, signaling an underlying health issue.
Recognizing the Signs of Androgen Excess
The physical manifestations of hyperandrogenism stem from the overstimulation of androgen-sensitive tissues. Hirsutism, the excessive growth of coarse, dark hair in areas typically associated with male hair patterns, is the most common clinical sign. This hair growth is measured using the modified Ferriman-Gallwey (mFG) scoring system, which evaluates nine body sites, including the upper lip, chin, chest, and upper back. A score of eight or higher is generally considered indicative of hirsutism.
The increased activity of the sebaceous glands, also influenced by androgens, often results in severe or persistent acne. This is caused by the excessive production of sebum, an oily substance that clogs pores and leads to inflammation. Androgenic alopecia, or female pattern hair loss (FPHL), is another frequent sign, characterized by diffuse thinning of hair on the crown and frontal scalp, while the hairline typically remains intact.
Excess androgens can significantly interfere with the reproductive system. Many women with hyperandrogenism experience menstrual irregularities, such as oligomenorrhea (infrequent periods) or amenorrhea (absent periods). This disruption occurs because the hormonal imbalance prevents the normal development and release of an egg, leading to anovulation. In severe cases, the sustained high levels of androgens can lead to virilization, which may include a deepening of the voice, clitoral enlargement, or a noticeable increase in muscle mass.
Primary Causes of Androgen Overproduction
Polycystic Ovary Syndrome (PCOS) is the most common cause of hyperandrogenism, affecting a significant percentage of women of reproductive age. PCOS is a complex endocrine-metabolic disorder centered on insulin resistance and hyperinsulinemia. When cells resist insulin, the pancreas produces excess insulin to compensate.
This excess insulin stimulates the ovaries to synthesize and release abnormal amounts of androgens. Hyperinsulinemia also reduces the liver’s production of sex hormone-binding globulin (SHBG), a protein that normally binds to and inactivates androgens. This results in a dramatic increase in biologically active, or “free,” testosterone, exacerbating physical symptoms.
Other conditions must also be considered. Non-classical Congenital Adrenal Hyperplasia (CAH) is a milder, late-onset genetic disorder caused by a partial deficiency of the 21-hydroxylase enzyme in the adrenal glands. This defect disrupts cortisol production, causing precursor hormones, such as 17-hydroxyprogesterone (17-OHP), to accumulate. These precursors are shunted into the androgen production pathway, leading to adrenal over-secretion.
Androgen-secreting tumors of the ovary or adrenal gland are rare. They cause a rapid onset and progression of hyperandrogenism, often accompanied by virilization symptoms. The sudden, pronounced rise in androgen levels differentiates a tumor from the more gradual onset of conditions like PCOS or non-classical CAH.
Medical Evaluation and Diagnosis
The evaluation process begins with a detailed physical examination to clinically assess the severity of hyperandrogenism, often using the modified Ferriman-Gallwey score. Blood tests are then performed to measure specific hormone levels and confirm the presence of biochemical hyperandrogenism. Total testosterone and free testosterone levels are measured, as free testosterone is the most biologically active form and correlates strongly with the severity of hirsutism.
Levels of dehydroepiandrosterone sulfate (DHEA-S), an androgen exclusively produced by the adrenal glands, are checked to help determine the androgen source. An elevated DHEA-S suggests an adrenal contribution, while normal DHEA-S with high testosterone often points toward an ovarian source.
To screen for non-classical CAH, the morning level of 17-hydroxyprogesterone (17-OHP) is measured. If the initial 17-OHP result is borderline, a specialized corticotropin (ACTH) stimulation test may be performed to confirm the diagnosis. Imaging studies, such as a pelvic ultrasound, are frequently used to evaluate ovarian morphology, particularly when PCOS is suspected.
Therapeutic Approaches for Management
Treatment for excess androgens is multifaceted, focusing on managing the symptoms while also addressing the underlying hormonal imbalance. Oral contraceptive pills (OCPs) are commonly used as a first-line pharmacological treatment, especially when contraception is also desired. OCPs suppress the production of androgens by the ovaries and increase the liver’s synthesis of SHBG, which binds to free testosterone, reducing its active circulating level.
Anti-androgen medications, such as spironolactone, are frequently added to the regimen to directly combat the effects of excess hormones at the tissue level. Spironolactone acts by competitively blocking the androgen receptors in target tissues, like the hair follicles and skin, thereby inhibiting the action of testosterone and DHT. It may also have a mild effect on reducing testosterone production and increasing SHBG.
For women with PCOS, lifestyle modifications are an integral part of the therapeutic strategy, particularly when insulin resistance is a factor. Weight management through dietary changes and regular physical activity can significantly improve insulin sensitivity. Improved insulin sensitivity helps to lower circulating insulin levels, which in turn reduces the ovarian production of androgens and can lead to a reduction in symptoms like hirsutism and menstrual irregularity.