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Review
. 2023 Feb 16;13(2):341.
doi: 10.3390/jpm13020341.

What Role do Androgens Play in Endometrial Cancer?

Petra Maček  1 , Nikolaus Molinari  1 , Monika Sobočan  1   2 , Jure Knez  1   2
Affiliations
Review

What Role do Androgens Play in Endometrial Cancer?

Petra Maček et al. J Pers Med. .

Abstract

The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of androgens. There are five different androgens produced in women: dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T) and dihydrotestosterone (DHT). The most potent hormones are T and DHT, the latter being mainly produced from T in peripheral tissues, including endometrium. Although they are considered to exert antiproliferative effects in many settings and the expression of their receptors is more often associated with a good prognosis in EC, it is still unknown in which specific settings androgens have carcinogenic or protective effects in EC.

Keywords: androgens; androstenedione; dehydroepiandrosterone; endometrial cancer; testosterone.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Androgens are produced mostly in the adrenal cortex and the ovaries from cholesterol, apart from DHT, which is mostly synthesized in the peripheral tissues (liver, adipose tissue and the pilosebaceous unit) through conversion from testosterone by 5α-reductase, this conversion also takes place in endometrial tissue After their production, they are released into the blood stream, and their serum concentration ratios are presented in the picture above in a descending order, which is opposite to their biological activity. Created with BioRender.com.
Figure 2
Figure 2
Testosterone can undergo a transformation into estrogen (E) and DHT. Transformation of E from androgens takes place in adipose tissue. Once T is already converted into DHT, the transformation can not be reversed, which leaves less T available for production of E. Increasing DHT relative to its precursor, testosterone, was associated with reduced risk of endometrial cancer, which suggests that higher endometrial cancer risk is associated with the potential for testosterone to be aromatized and that for the etiology of most endometrial cancers, the estrogenic pathway is more important than the androgenic. Created with BioRender.com.
See this image and copyright information in PMC

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