Effects of aromatase inhibition in hypogonadal older men: a randomized, double‐blind, placebo‐controlled trial

Burnett-Bowie, Sherri-Ann M.; Roupenian, Kristen C.; Dere, Melissa E; Lee, Hang; Leder, Benjamin Z.

doi:10.1111/j.1365-2265.2008.03327.x

Cited by 60 publications

(59 citation statements)

References 44 publications

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“…Subsequent studies have corroborated these findings and have linked estradiol deficiency to more rapid rates of bone loss in older men (7,8). Additionally, treatment with dihydrotestosterone, a nonaromatizable androgen that reduces estradiol levels, and aromatase inhibitors provoke substantial bone mineral density loss in men (9,10). Furthermore, there is a stronger inverse association between estrogen level and fractures in older men than testosterone (11,12).…”

Section: Introductionsupporting

confidence: 53%

Battle of the sex steroids in the male skeleton: and the winner is…

Weber¹

2016

Journal of Clinical Investigation

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Section: Introductionsupporting

confidence: 53%

Battle of the sex steroids in the male skeleton: and the winner is…

Weber¹

2016

Journal of Clinical Investigation

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“…These include an increase in intratesticular testosterone concentrations together with increased circulating levels of testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH). Analogous effects were observed in young male volunteers, elderly men, elderly men with borderline hypogonadism and MBC patients [50][51][52][53][54]. Thus, increased androgen levels during AI therapy represent a sort of "endocrine side effect", influencing MBC biology in two different ways: i) the excess of substrate for aromatization outcompetes the pharmacological effects of AIs, ii) the excess of androgens directly stimulates AR-expressing cancer cells.…”

Section: Endocrine Concepts Supporting Therapeutic Androgen Suppressimentioning

confidence: 80%

Androgen receptor and antiandrogen therapy in male breast cancer

et al. 2015

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Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients.

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“…It is well established that androgens increase muscle mass in men (26)(27)(28), while the possible role of estrogens and ERs for muscle mass in men remains unclear. Clinical trials investigating the effects of aromatase inhibition in older men showed no effect of the intervention on body composition or muscle strength (29,30) and, thus, did not support an important role of serum E 2 levels for lean mass in men. Nevertheless, animal studies have indicated that not only AR activation but also ER activation modulates lean mass (31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Serum estradiol is associated with lean mass in elderly Swedish men

Vandenput

Mellström

Karlsson

et al. 2010

European Journal of Endocrinology

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Objective: Association studies in men have shown that androgens are inversely related to fat measures, while the relation between sex steroids and lean mass remains unclear. We, therefore, investigated the associations between serum sex steroid levels and body composition in elderly men with a main focus on lean mass measures. Design and methods: A cross-sectional survey of a population-based cohort of 3014 elderly men, aged 69-80 years (Osteoporotic Fractures in Men study, Sweden). Serum levels of testosterone and estradiol (E 2 ) were measured by mass spectrometry, sex hormone-binding globulin (SHBG) levels were measured by IRMA, and measures of body composition were obtained by dual-energy X-ray absorptiometry. Results: Total as well as free serum testosterone associated independently inversely (P!0.001), while total as well as free serum E 2 associated independently directly (P!0.001) with total body fat mass and trunk fat mass. Serum SHBG associated independently inversely with central fat distribution. Serum E 2 and free E 2 but not serum testosterone or free testosterone levels associated positively with lean mass (P!0.01). Elderly men within the lowest quartile of free E 2 had 0.5 kg less lean mass in the legs than subjects within the highest quartile, while the subjects in the different quartiles of free testosterone did not differ in lean mass. Conclusions: Serum E 2 , but not serum testosterone, is directly associated with lean mass in this large study of elderly Swedish men. In addition, serum SHBG is associated with central fat distribution and we confirmed that serum testosterone is inversely associated with fat mass.

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Effects of aromatase inhibition in hypogonadal older men: a randomized, double‐blind, placebo‐controlled trial

Abstract: Anastrozole administration normalized androgen production in older hypogonadal men and decreased estradiol production modestly. These alterations did not improve body composition or strength.

Cited by 60 publications

References 44 publications

Battle of the sex steroids in the male skeleton: and the winner is…

Battle of the sex steroids in the male skeleton: and the winner is…

Androgen receptor and antiandrogen therapy in male breast cancer

Serum estradiol is associated with lean mass in elderly Swedish men

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