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Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations
Franck Mauvais-Jarvis, Sarah H. Lindsey
Franck Mauvais-Jarvis, Sarah H. Lindsey
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Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations

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Abstract

Testosterone (T) and 17β-estradiol (E2) are produced in male and female humans and are potent metabolic regulators in both sexes. When E2 and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by E2 and T for metabolic function human females and males. In females, E2 is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T’s conversion to E2 is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and E2 are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study.

Authors

Franck Mauvais-Jarvis, Sarah H. Lindsey

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Figure 1

Origin of T and E2 in males and females.

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Origin of T and E2 in males and females.
(A) In males, all T is produced...
(A) In males, all T is produced by Leydig cells of the testis. Most E2 (80%) is formed via aromatization of circulating T in the periphery. The testes directly produce approximately 20% of circulating E2. (B) In females of reproductive age, the granulosa cells of the ovaries produce E2, the major circulating estrogen. T is produced by the ovary (25%), the adrenal gland (25%), and in peripheral tissues (50%) following conversion from circulating androstenedione (A4, an androgen that is equally produced by the ovary and the adrenal gland). (C) After menopause, estrone (E1) becomes the major circulating estrogen and is produced by aromatization from A4 (mainly produced by the adrenal gland) in adipose tissue. E1 serves as a reservoir of E2. T is mainly produced by the ovaries (50%) and peripheral conversion of A4 (40%). 17β-HSD, 17β-hydroxysteroid dehydrogenase.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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