Artigo Revisado por pares

Incidence of Increased Androgen Levels in Patients Suffering from Acne

1998; Karger Publishers; Volume: 196; Issue: 1 Linguagem: Inglês

10.1159/000017867

ISSN

1421-9832

Autores

Christina Henze, B. Hinney, W. Wuttke,

Tópico(s)

melanin and skin pigmentation

Resumo

Hyperandrogenemia in women is often associated with sterility [1]. More than 50% of women attending infertility clinics have either elevated serum testosterone or dehydroepiandrosterone sulfate (DHEAS) levels. These androgens can be aromatized in fat tissue, particularly of the feminine type (i.e. fat distribution around the thigh and the hip). This results in constantly increased estrogen (particularly estrone) levels which feedback into the hypothalamus to cause the increased release of pituitary luteinizing hormone (LH). Under special metabolic conditions (latent diabetes mellitus with increased somatomedin C levels), this may result in the development of polycystic ovarian disease (PCOD) [2]. Under these conditions multiple follicles in the ovary develop but do not ovulate, the ovarian capsule thickens and the increased serum LH levels stimulate ovarian testosterone production. This testosterone is then again aromatized which results in a vicious circle with the end effect of hard-to-treat sterility due to PCOD.The pilosebaceous unit in the skin is regulated by androgens and there is increasing evidence that in cases of severe acne adrenal and/or ovarian androgen production is exaggerated [3]. Hence we felt that the above deleterious effects of androgens on ovarian function may also reflect an early androgenization of the pilosebaceous unit. Therefore we studied the circulating testosterone, DHEAS and LH levels in patients suffering from seborrhea, acne, hirsutism and/or androgenetic alopecia. The results obtained from patients suffering from acne are shown in table 1. The upper range of normality for testosterone is 0.4–0.6 ng/ml, for DHEAS 3,000 ng/ml and for LH 10 mU/ml. It can be seen that a good number (>30%) of acne patients has elevated testosterone and/or DHEAS levels. Another group of acne patients has normal androgen levels (38%), whereas 32% have androgen levels in the upper range of normality. In 22% of the acne patients, serum LH was elevated which may be an indication that the vicious circle described above (increased androgens – increased estrogen production in the fat – increased pituitary LH release – further increased ovarian androgen production) may already be in progress and that these women are possibly on the way to develop PCOD. Another aspect, also detailed in table 1, deserves discussion. There is a good number of patients with severe acne although their serum androgen levels are in the range of normality. This apparent discrepancy is discussed as follows: neither testosterone nor DHEAS have the strongest androgenic potency in the pilosebaceous unit, but a locally present enzyme which reduces testosterone to 5α-dihydrotestosterone causes the local production of the most potent androgen 5α-dihydrotestosterone. There is some evidence that 5α-reductase in patients with severe signs of androgenization in the skin may be overactive. An additional or alternative explanation is an oversensitivity of the androgen receptor in the pilosebaceous unit.Treatment of androgenization symptoms of the skin with endocrine tools follows at present two strategies: (1) inhibition of pituitary LH secretion to prevent increased ovarian androgen production or (2) blockade of the androgen receptors in the pilosebaceous unit with antiandrogens. Pituitary LH secretion can be very effectively blocked by all oral contraceptives (OCs) which combine a potent estrogen (in most OCs this is ethinylestradiol) with a potent progestin. Some antiandrogens have also powerful progestin-like activities. Therefore the combination with ethinylestradiol and a progestationally active antiandrogen (e.g. cyproterone acetate or chlormadinone acetate) is a powerful tool to act as an OC and to block the androgen receptor. These OCs are commercially available and highly effective to treat high LH secretion by the pituitary. Thereby the ovarian testosterone production is also reduced. In addition, the antiandrogens block the androgen receptor in the pilosebaceous unit and prevent thereby the action of the remaining androgens (table 1). Treatment of acne with these OCs is highly effective and a rapid reduction of acne is achieved within several months. In addition, we hope that with such a treatment the development of sterility due to the development of PCOD can be prevented. However, long-term controlled prospective studies are necessary to prove this hypothesis.Some patients with severe hyperandrogenism have also increased 17-OH-progesterone levels, which is a marker enzyme for the adrenogenital syndrome. In these patients, a glucocorticoid treatment by experienced endocrinologists is necessary. In very few patients an adrenal or ovarian androgen-producing tumor is the reason for increased androgen action in the skin which needs surgical correction.Taken all together, dermatologists should know the endocrine disorders described above in some detail and a close collaboration with the gynecological endocrinologist is recommended.

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