Androgen excess: Investigations and management

Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman–Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response.

Highlights

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    Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS).

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    Total and free testosterone (T) should be measured in patients with unclear hirsutism.

  • •

    Assessment of total and free T requires use of the highest quality assays available.

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    Management of clinical hyperandrogenism involves androgen suppression or blockade.

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    Medical treatment should be combined with cosmetic treatment for optimal efficacy.

Androgen biosynthesis and metabolism in women

Androgens are produced de novo from cholesterol in the ovarian theca and the adrenal cortex (zonae reticularis). Additionally, circulating androgen precursors can be metabolized into more potent androgens in peripheral tissues such as the liver, adipose tissue, and the pilosebaceous unit (PSU) ( Fig. 1 ).

Fig. 1
Principal pathways of androgen synthesis and catabolism (modified from Azziz et al, 1989 ). Enzymatic activities: (1) 3β-hydroxysteroid dehydrogenase (3β-HSD) c ; (2) 17α-hydroxylase d ; (3) 17,20-lyase d ; (4) 17β-hydroxysteroid dehydrogenase e ; (5) aromatase f ; (6) 5α-reductase g ; (7) 5β-reductase h ; (8) 3β-oxoreductase i ; and (9) 3α-oxoreductase j . a In the gonads, the 17β-hydroxysteroid dehydrogenase reaction predominantly produces 17β-dehydrogenated products (androstenediol and testosterone), whereas the reverse is true in peripheral tissues. b Aldosterone, etiocholanolone, and DHEA are the principal urinary metabolites of androgens. c In humans there are two isozymes of 3β-hydroxysteroid dehydrogenase/Δ 5-4 isomerase (3β-HSD) (EC 1.1.1.145), 3β-HSD type I, expressed in placenta and peripheral tissues, and 3β-HSD type II, expressed in the adrenal gland, ovary, and testis, encoded by HSD3B1 and HSD3B2 , resp. In androgen biosynthesis, HSD3B2 dominates. d Both 17α-hydroxylase and 7,20-lyase activities are determined by cytochrome P450c17A1 (EC 1.14.14.19), an enzyme that in humans is encoded by CYP17A1 . Note that, in humans, Δ 4 17,20-lyase activity (catalyzing the direct interconversion of androstenedione and testosterone) is almost nonexistent under normal conditions; Δ 5 17,20-lyase (catalyzing the interconversion of DHEA and androstenediol) is the dominant activity and, thus, determines the preferred pathway to testosterone synthesis from cholesterol. e 17β-dehydrogenase (EC 1.1.1.239) is an enzyme that in humans has a number of isozymes, although in androstenedione–testosterone and estrone–estradiol interconversion, the types 1 and 2, encoded by HSD17B1 and HSD17B2 , are the most predominant. f Aromatase activity is determined by cytochrome P450c19 or P450arom (EC 1.14.14.1), encoded by the CYP19A1 . g 5α-reductase activity (EC 1.3.99.5) is determined by three isozymes, whose content varies in different tissues with age: steroid 5α-reductase type 1, 2, and 3, encoded by SRD5A1 , SRD5A2 and SRD5A3 , respectively. Androgen 5α-reductase activity is primarily determined by 5α-reductase types 1 and 2. h 5β-reductase activity is determined byΔ 4 -3-oxosteroid 5β-reductase (EC 1.3.1.3), encoded by AKR1D1 (previously SRD5B1) . i 3α-oxoreductase activity is determined 3α-hydroxysteroid dehydrogenase (3α-HSD) (EC 1.1.1.50) is encoded by AKR1C4 . j 3β-oxoreductase activity is determined by 3β-hydroxy-5α-steroid:NADP + 3-oxidoreductase (EC 1.1.1.278) encoded by AKR1D1 .

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Nov 6, 2017 | Posted by in OBSTETRICS | Comments Off on Androgen excess: Investigations and management

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