What are the causes of mild testosterone elevation in two female patients with hair fall and acne, despite normal hormonal investigations and regular menses?

From the Guidelines

Mild testosterone elevation in female patients with hair fall and acne, despite normal hormonal investigations and regular menses, can be managed with medications like spironolactone (50-200 mg daily) or combined oral contraceptives containing drospirenone or cyproterone acetate, as these have been shown to decrease testosterone levels and improve symptoms. The causes of mild testosterone elevation in these patients can be multifactorial, including polycystic ovary syndrome (PCOS) with subtle hormonal imbalances, adrenal hyperplasia, insulin resistance, obesity, and certain medications like anabolic steroids or danazol 1. Lifestyle factors such as stress, poor diet, and lack of exercise can also contribute to hormonal fluctuations. Genetic predisposition plays a role in determining sensitivity to androgens, meaning some women experience symptoms like acne and hair loss even with testosterone levels at the upper end of normal range.

Other potential causes include:

• Thyroid dysfunction
• Hyperprolactinemia
• Early perimenopause
• Cushing's syndrome
• Androgen-secreting tumors of the ovary or adrenal gland
• Exogenous androgens
• Nonclassic (late-onset) congenital adrenal hyperplasia
• Acromegaly
• Genetic defects in insulin action
• Primary hypothalamic amenorrhea
• Primary ovarian failure
• Prolactin disorders

Management should focus on addressing the underlying cause, which may include:

• Weight management
• Stress reduction
• Dietary changes
• Medications like spironolactone (50-200 mg daily) or combined oral contraceptives containing drospirenone or cyproterone acetate
• Metformin (500-2000 mg daily) if insulin resistance is present
• Topical treatments like minoxidil 2-5% for hair loss and retinoids for acne can help manage symptoms. According to a recent study 1, spironolactone is conditionally recommended for acne treatment based on moderate certainty evidence from 8 studies, and its use may represent an opportunity to improve antimicrobial stewardship and outcomes in patients with acne. Additionally, combined oral contraceptives containing estrogen and progestin have been shown to decrease free testosterone by 40-50% on average and improve acne symptoms 1.

It is essential to monitor patients regularly to assess treatment efficacy and adjust as needed, considering the potential side effects of these medications, such as menstrual irregularities, breast tenderness, and diuresis with spironolactone, and the risks associated with combined oral contraceptives, such as venous thromboembolism and breast cancer 1.

From the Research

Explanation of Mild Testosterone Elevation

The mild elevation of testosterone levels in two female patients with hair fall and acne, despite normal hormonal investigations and regular menses, can be attributed to several factors.

• The patients' symptoms of hair fall and acne may be indicative of hyperandrogenism, which can be caused by various factors, including polycystic ovary syndrome (PCOS) 2, 3.
• Studies have shown that women with acne have higher levels of androgens, including total and free testosterone, compared to those without acne 4, 5.
• The presence of acne and hirsutism in women can be a sign of underlying hyperandrogenism, and PCOS is a common cause of hyperandrogenism in women of reproductive age 2, 6, 3.
• The fact that the patients have regular menses does not rule out the possibility of PCOS, as some women with PCOS may have regular menstrual cycles 2, 3.

Causes of Mild Testosterone Elevation

The causes of mild testosterone elevation in these patients can be attributed to:

• Polycystic ovary syndrome (PCOS), which is a common endocrine disorder in women of reproductive age 2, 6, 3.
• Other underlying causes of hyperandrogenism, such as congenital adrenal hyperplasia or androgen-secreting tumors, although these are less common 4, 6.
• The patients' androgen profiles, including elevated levels of total and free testosterone, may also contribute to their symptoms of hair fall and acne 5, 6.
• The use of certain medications or hormonal therapies may also affect testosterone levels, although this is not mentioned in the patient's history 4, 6.

Clinical Implications

It is essential to evaluate these patients further to determine the underlying cause of their hyperandrogenism and to rule out any other potential causes of their symptoms.

• A thorough medical history, physical examination, and laboratory tests, including hormonal profiles and pelvic ultrasonography, may be necessary to confirm the diagnosis of PCOS or other underlying conditions 2, 3.
• Treatment options, such as hormonal therapies or anti-androgen medications, may be considered to manage the patients' symptoms and underlying condition 4, 6.