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Aromatase inhibitors

Aug. 1, 2019

Aromatase is an enzyme that converts androgens into estrogens. Aromatase activity occurs mainly in the sexual glands and the placenta, but also in the brain, the fatty tissues, the muscles, the hair, and the bones [1].

Aromatase inhibitors can be classified as substances known as anti-estrogens. Typically, they are used for the treatment of post-menopausal female breast cancer. The indications for men are related to infertility treatments while those for boys are related to body growth regulation. Sometimes aromatase inhibitors are also used instead of testosterone for the treatment of low male testosterone, helping to improve the male testosterone/estradiol (T/E) ratio [1, 2, 3, 4]. Aromatase inhibitors work especially in situations where a man has normal testosterone values, but an abnormal T/E ratio [5.]

In the case of men, aromatase inhibitors are not associated with potentially rising estrogen levels of the kind which may occur with the use of selective estrogen receptor modulators (SERMs) [3, 5].

Currently, there are three different aromatase inhibitors available in Finland by prescription. The active ingredients of these three drugs are the following: anastrozole, exemestane, and letrozole. Exemestane is steroidal, but anastrozole and letrozole are non-steroidal [2]. The binding of a non-steroidal aromatase inhibitor to aromatase protein is reversible, whereas the binding of a steroidal one is irreversible [6].

Purpose of use as a doping substance

Because testosterone and anabolic steroids are aromatized into estrogens, consequent gynecomastia (breast enlargement) may occur in men, as well as low gonadotrophin and testosterone levels [1, 7]. Users seek to prevent these changes with aromatase inhibitors. Trials of aromatase inhibitors have not shown them to be very potent in the treatment of male gynecomastia [1].

Aromatase inhibitors do not fully normalize the estrogen count in men. Aromatase inhibitors also raise the levels of testosterone, the luteinizing hormone, and the follicle-stimulating hormone by lowering the estrogen level. With mere aromatase inhibitors, testosterone levels should not rise to supraphysiological levels [1, 8]. For some test subjects, however, 2.5 mg of letrozole once a week led to a rise in their testosterone to the supraphysiological level [9].

Adverse effects

The most serious potential adverse effect of aromatase inhibitors is related to skeletal health. They may lower bone mineral density and increase the risk of a fracture [1, 2]. Estrogen is an important hormone not only for women, but for male bone health as well [10].

When used for medical purposes, some of the reported adverse effects include headaches, hot flashes, nausea, eczema, arthralgia, stiffness in the joints, arthritis, and asthenia [2]. Adverse effects have rarely been found in male infertility treatments [3].

Some known trade names (8/2019): Anastrozol Sandoz, Anazol, Aromasin, Exemestan, Femar, Letrozol.

 

Joni Askola
Master of Health Sciences (MHSc)
Dopinglinkki

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[2] Duodecim lääketietokanta. 2019. Aromataasin estäjät. Terveysportti

[3] Schlegel P. Aromatase inhibitors for male infertility. Fertility and Sterility. 2012; 98(6): 1359–1362

[4] Mauras N, Ross J, Gagliardi P, Yu M, Hossain J, Permuy J, Damaso L, Merinbaum D, Sing R, Gaete X, Mericq V. Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic, short stature. JCEM. 2016;101(12):4984–4993

[5] Ring J, Lwin A, Köhler T. Current medical management of endocrine-related male infertility. Asian J Androl. 2016:18(3):357–363

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[8] Handelsman D. Indirect androgen doping by oestrogen blockade in sports. Br J Pharmacol. 2008;154(3):598–605

[9] Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol. 2008;158(5):747–7

[10] Khosla S, Melton J, Riggs L. Estrogen and the male skeleton. J Clin Endo Metab. 2002;87(4):1443–1450

[11] Vanderschueren D, Laurent M, Claessens F, Gielen E, Lagerquist M, Vandenput L, Börjesson A, Ohlsson C. Sex steroid actions in male bone. Endocr Rev. 2014;35(6):906-960



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