What causes low testosterone in females?

Causes of Low Testosterone in Females

Primary Causes of Female Testosterone Deficiency

Low testosterone in females most commonly results from conditions that directly impair ovarian or adrenal androgen production, including oophorectomy, premature ovarian failure, adrenal insufficiency, hypopituitarism, and the use of oral estrogen therapy or high-dose corticosteroids. 1, 2

Surgical and Ovarian Causes

• Bilateral oophorectomy is the most significant cause, resulting in an approximately 50% decline in testosterone and androstenedione levels, as the ovaries normally contribute about half of daily testosterone production (approximately 150 μg of the total 300 μg produced daily). 1, 3
• Premature ovarian failure leads to testosterone deficiency through loss of ovarian androgen production. 1, 2
• Turner's syndrome causes testosterone deficiency due to gonadal dysgenesis. 1

Adrenal Causes

• Adrenalectomy eliminates the adrenal contribution to testosterone production (normally about 150 μg daily). 1
• Adrenal disease including Addison's disease impairs adrenal androgen synthesis. 1, 2
• High-dose corticosteroid therapy suppresses adrenal androgen production through negative feedback on the hypothalamic-pituitary-adrenal axis. 1, 2

Pituitary and Hypothalamic Causes

• Hypopituitarism reduces gonadotropin secretion (LH and FSH), leading to decreased ovarian testosterone production. 1, 2
• Pituitary disease disrupts the hypothalamic-pituitary-gonadal axis, impairing ovarian androgen synthesis. 1

Medication-Induced Causes

• Oral estrogen preparations (including oral contraceptives and oral hormone replacement therapy) cause testosterone deficiency through two mechanisms: elevating sex hormone-binding globulin (SHBG), which reduces free testosterone availability, and suppressing gonadotropins, which decreases ovarian testosterone production. 1, 2, 3
• This effect is specific to oral estrogen; transdermal estrogen does not significantly elevate SHBG. 1

Age-Related Decline

• Natural aging causes a progressive decline in testosterone levels, with a 50% reduction from the early 20s to the mid-40s, meaning age-related androgen insufficiency can occur in women in their late 30s and 40s, not just postmenopausally. 4
• Natural menopause may contribute to testosterone deficiency in some women, though the decline is less dramatic than with surgical menopause. 1

Other Contributing Conditions

• HIV infection can impair both ovarian and adrenal androgen production. 1
• Chronic liver disease may affect testosterone metabolism and SHBG levels, though this primarily impacts bioavailable testosterone rather than total production. 5

Diagnostic Approach

The diagnosis requires measuring both total testosterone and SHBG to calculate free or bioavailable testosterone, as SHBG elevation can mask adequate total testosterone production while causing functional deficiency. 2, 4

• Free testosterone or the total testosterone/SHBG ratio provides a better index of androgen status than total testosterone alone. 5, 2, 4
• A total testosterone/SHBG ratio <0.3 indicates hypogonadism in the context of chronic liver disease. 5
• Testosterone measurements should be obtained in the morning due to diurnal variation. 5
• In premenopausal women with menstrual irregularity or evidence of hypogonadism, assess serum estradiol and LH/FSH alongside testosterone. 5

Clinical Manifestations

The syndrome of female androgen deficiency presents with decreased libido, diminished sense of well-being, persistent unexplained fatigue, and blunted motivation in a woman who is estrogen-replete. 2, 4, 3