Excess ovarian androgen release syndrome

Overview

Excess Ovarian Androgen Release Syndrome refers to a condition in which the ovaries produce abnormally high levels of androgens (male hormones such as testosterone), leading to a range of symptoms associated with androgen excess. Although androgens are naturally present in women in small amounts, excessive production can result in hormonal imbalances that affect menstrual regularity, skin health, fertility, and physical appearance. This syndrome is often linked with underlying disorders such as polycystic ovary syndrome (PCOS), ovarian tumors, or other functional ovarian abnormalities.

Causes

The most common causes of excess ovarian androgen production include:

• Polycystic Ovary Syndrome (PCOS): The most frequent cause of chronic hyperandrogenism, characterized by multiple ovarian cysts, irregular ovulation, and insulin resistance.

• Ovarian androgen-secreting tumors: Rare tumors such as Sertoli-Leydig cell tumors or thecomas that actively produce androgens.

• Congenital adrenal hyperplasia (non-classic form): Can sometimes involve ovarian overproduction as a secondary effect.

• Ovarian stromal hyperthecosis: A condition seen in older women where the ovarian stroma becomes hyperactive and increases androgen production.

• Hyperinsulinemia: Elevated insulin levels can stimulate ovarian androgen secretion, especially in the context of insulin resistance.

Symptoms

Symptoms of excess ovarian androgen release are due to elevated levels of testosterone and other androgens in the female body. Common clinical signs include:

• Hirsutism: Excessive hair growth in areas where men typically grow hair (face, chest, back)

• Acne and oily skin

• Scalp hair thinning or female-pattern hair loss (androgenic alopecia)

• Menstrual irregularities: Oligomenorrhea (infrequent periods), amenorrhea (absence of periods), or irregular cycles

• Infertility: Due to anovulation or disrupted ovulatory cycles

• Voice deepening and clitoromegaly: Rare but can occur in severe cases, especially with androgen-producing tumors

• Weight gain or central obesity: Often associated with insulin resistance

Diagnosis

Diagnosis involves a combination of clinical evaluation, laboratory tests, and imaging studies to determine the source of androgen excess. Key steps include:

• Hormonal assays:

  • Elevated total and free testosterone

  • Androstenedione, DHEA-S, and LH/FSH ratio may also be assessed

• Pelvic ultrasound: To evaluate for polycystic ovaries or detect ovarian masses

• MRI or CT scan: In cases where a tumor is suspected

• Glucose tolerance test or fasting insulin: To assess for insulin resistance

• Rule out adrenal causes: By checking DHEA-S and performing imaging if adrenal tumors are suspected

A thorough evaluation helps differentiate between functional causes (e.g., PCOS) and neoplastic causes (e.g., tumors).

Treatment

Treatment depends on the underlying cause of androgen excess and the severity of symptoms. Options include:

• Hormonal therapy:

  • Combined oral contraceptives (COCs): Regulate menstrual cycles and suppress ovarian androgen production

  • Anti-androgens (e.g., spironolactone, flutamide): Reduce hirsutism and acne

• Insulin sensitizers: Such as metformin, especially in cases associated with PCOS or insulin resistance

• Weight management: Through diet and exercise to improve insulin sensitivity and hormonal balance

• Fertility treatments: Including ovulation induction (e.g., with clomiphene or letrozole) for women desiring pregnancy

• Surgical intervention: Required in cases of androgen-secreting tumors (e.g., oophorectomy)

• Cosmetic treatments: For hirsutism (e.g., laser hair removal, electrolysis)

Prognosis

The prognosis for women with excess ovarian androgen release syndrome depends on the underlying cause and the timeliness of diagnosis and treatment. PCOS-related androgen excess can be managed effectively with lifestyle modifications and medications, though symptoms may recur if treatment is stopped. Tumor-related androgen excess typically resolves with surgical removal of the tumor. Long-term management may be needed to address metabolic complications, fertility issues, and emotional well-being. Early intervention offers the best outcomes in terms of symptom control and quality of life.