Approach to Investigation of Hyperandrogenism in a Postmenopausal Woman

Abstract

Postmenopausal hyperandrogenism is a condition caused by relative or absolute androgen excess originating from the ovaries and/or the adrenal glands. Hirsutism, in other words, increased terminal hair growth in androgen-dependent areas of the body, is considered the most effective measure of hyperandrogenism in women. Other symptoms can be acne and androgenic alopecia or the development of virilization, including clitoromegaly. Postmenopausal hyperandrogenism may also be associated with metabolic disorders such as abdominal obesity, insulin resistance, and type 2 diabetes. Mild hyperandrogenic symptoms can be due to relative androgen excess associated with menopausal transition or polycystic ovary syndrome, which is likely the most common cause of postmenopausal hyperandrogenism. Virilizing symptoms, on the other hand, can be caused by ovarian hyperthecosis or an androgen-producing ovarian or adrenal tumor that could be malignant. Determination of serum testosterone, preferably by tandem mass spectrometry, is the first step in the endocrine evaluation, providing important information on the degree of androgen excess. Testosterone >5 nmol/L is associated with virilization and requires prompt investigation to rule out an androgen-producing tumor in the first instance. To localize the source of androgen excess, imaging techniques are used, such as transvaginal ultrasound or magnetic resonance imaging (MRI) for the ovaries and computed tomography and MRI for the adrenals. Bilateral oophorectomy or surgical removal of an adrenal tumor is the main curative treatment and will ultimately lead to a histopathological diagnosis. Mild to moderate symptoms of androgen excess are treated with antiandrogen therapy or specific endocrine therapy depending on diagnosis. This review summarizes the most relevant causes of hyperandrogenism in postmenopausal women and suggests principles for clinical investigation and treatment.

Keywords: androgen-producing tumor; hirsutism; hyperandrogenism; ovarian hyperthecosis; postmenopausal women; virilization.

Figure 1.

The Ludwig scale of androgen-dependent frontotemporal baldness type I to III, where type III is the most severe form of androgenic alopecia also called “Hippocratic baldness.”

Figure 2.

Clinical signs of severe hyperandrogenism and virilizing symptoms of hyperandrogenism in a perimenopausal and postmenopausal women including (A) androgenic alopecia, (B) breast atrophy and hirsutism, and (C) clitoromegaly.

Figure 3.

Algorithm for principles of investigation and treatment of different causes of hyperandrogenism in postmenopausal women. The cut-off of 5 nmol/L for serum testosterone is based on LC–MS/MS measurement. ACTH, adrenocorticotropic hormone; CT, computed tomography; GnRH, gonadotropin-releasing hormone; 17-OHP, 17-hydroxyprogesterone; MRI, magnetic resonance imaging; NC CAH, nonclassical congenital adrenal hyperplasia; PCOS, polycystic ovary syndrome.