Approach to androgen excess in women: Clinical and biochemical insights

Abstract

Androgen excess in women typically presents clinically with hirsutism, acne or androgenic alopecia. In the vast majority of cases, the underlying aetiology is polycystic ovary syndrome (PCOS), a common chronic condition that affects up to 10% of all women. Identification of women with non-PCOS pathology within large cohorts of patients presenting with androgen excess represents a diagnostic challenge for the endocrinologist, and rare pathology including nonclassic congenital adrenal hyperplasia, severe insulin resistance syndromes, Cushing's disease or androgen-secreting tumours of the ovary or adrenal gland may be missed in the absence of a pragmatic screening approach. Detailed clinical history, physical examination and biochemical phenotyping are critical in risk-stratifying women who are at the highest risk of non-PCOS disorders. Red flag features such as rapid onset symptoms, overt virilization, postmenopausal onset or severe biochemical disturbances should prompt investigations for underlying neoplastic pathology, including dynamic testing and imaging where appropriate. This review will outline a proposed diagnostic approach to androgen excess in women, including an introduction to androgen metabolism and provision of a suggested algorithmic strategy to identify non-PCOS pathology according to clinical and biochemical phenotype.

Evaluation of Hormonal Factors in Acne Vulgaris and the Course of Acne Vulgaris Treatment with Contraceptive-Based Therapies in Young Adult Women

“…These results are corroborated by the clinically known facts of more severe symptoms of sebum secretion by CRH and ACTH receptor stimulation of sebocytes. In addition, there is increased androgen secretion during ACTH-dependent Cushing’s syndrome compared to the case of adrenal adenoma, which is probably related to the simultaneous stimulation by ACTH of the adrenal cortex cells responsible for adrenal steroidogenesis and excessive secretion of DHEA and testosterone [ 53 , 54 ]. The observed correlations should signal the need for more in-depth knowledge on this topic in young adult women with acne.…”

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency

“…Considering the impact on a possible offspring, differential diagnosis between POS and non-classic CAH is essential [ 68 , 74 ]. While clinical manifestations may be similar, the clue in order to differentiate CAH from POS is to perform the panel of androgens assays [ 78 , 79 ]. A practical tool of differentiation remains 17OHP; however, baseline values may be normal in both CAH and POS, thus an ACTH stimulation test might be useful [ 80 ].…”

“…Notably, from an epidemiological perspective, the most common condition causing androgen excess is POS, affecting 10% of all females with reproductive age; while hirsutism relates to idiopathic forms followed by POS in 85% of cases [ 81 ]. The other conditions that represent 10–15% of disorders underling androgen excess are, apart from non-classical forms of CAH, Cushing syndrome, severe insulin resistance syndromes, and ovarian tumours with androgens overproduction [ 79 , 82 , 83 ]. The non-classical forms of CAH (regarding any type of enzyme defect, but, mostly, 21OH deficiency) represent 0.6 to 9% of all cases with androgen excess [ 84 ].…”

Differentiating Polycystic Ovary Syndrome from Adrenal Disorders

“…In peripheral tissues, 11KA4 is activated by AKR1C3 to produce 11-ketotestosterone (11KT); 11-oxygenated androgens account for the bulk of the circulating androgens in PCOS, early adrenarche, and congenital adrenal hyperplasia (CAH). 11KT and 11-ketodihydrotestosterone (11KDHT) are potent androgens that bind to androgen receptors with high affinity, such as testosterone and DHT [ 24 ].…”