Risks of Menopausal Androgen Supplementation

Abstract

There is increasing interest in the use of menopausal androgen replacement therapy (MART) in symptomatic women undergoing natural or surgical menopause. However, the efficacy of MART in alleviating these symptoms compared to traditional estrogen/progestin hormone replacement therapy remains a subject of debate. Accordingly, attention must be focused on the side-effects of the various MART preparations. The dose, alkylation, and route of administration of these compounds influences the development of side effects. While all androgens are potential virilizing agents, alkylated compounds have an additional risk of inducing severe hepatic consequences, regardless of their route of administration. Fortunately, the lower doses administered to women compared to men has not resulted in significant hepatic events. Generation of an adverse lipoprotein profile is possible but is not addressed in this article. Thus, virilizing and cutaneous side effects remain the primary concern. While some observational studies indicate acne and/or hirsutism are evident in up to 38% and 36% of oral methyltestosterone-treated patients, respectively, other studies performed in a prospective fashion suggest a much lower incidence of approximately 5%. Other reported virilizing effects include deepening of the voice and clitoromegaly. Additional concerns are related to risks of developing endometrial hyperplasia when MART is used in conjunction with estrogens. Fortunately, concomitant progestin administration is protective. Finally, there is a theoretical concern that MART may increase the risk of developing breast cancer but this has not been demonstrated in clinical practice. Overall, the safety profile of MART appears to be acceptable when dosing avoids supraphysiologic testosterone levels.

Safety of testosterone treatment in postmenopausal women

“…The primary safety issues are androgenic side effects; adverse effects on the cardiovascular system; stimulation of the endometrium and breast leading to neoplasia; hepatotoxicity; induction or aggravation of sleep apnea; and behavioral effects (8)(9)(10)(11). Some of these concerns are based on problems that have been found in males receiving pharmacological doses of T or anabolic steroids, in women with hyperandrogenic polycystic ovaries, and from the Heart and Estrogen/ Progestin Replacement Study (HERS) and Women's Health Initiative (WHI), in which estrogens and progestins were found to have adverse effects (12,13).…”

“…Since most of the studies that evaluated T therapy in postmenopausal women did so in the presence of estrogen (if the patient had undergone a hysterectomy) or estrogen and a progestin (if she had undergone a natural menopause), there has been a concern that adding androgen may compound any adverse cardiovascular effect of the other sex steroid hormones. Additionally, since T is aromatized into E 2 in a variety of peripheral tissues through the action of aromatase, it has been hypothesized that giving T will result in greater tissue exposure to estrogen (10). Thus, it is speculated that estrogen-induced problems may be exacerbated with androgen therapy in which an aromatizable androgen such as T is given.…”

“…Of interest, up to 2 years were required for the T levels to fall to within the normal range in some of these women (60). Clitoromegaly has also been occasionally noted in women receiving T implants (10). In female-to-male transsexuals who received 100-400 mg of intramuscular testosterone cypionate every month, the stretched clitoral length increased from an average of about 1.25 cm to approximately 5 cm over time, with a plateau occurring at about one year (58).…”

Testosterone Treatment in Women – An Overview

“…They all seem to be dose-dependent and rarely occur when testosterone levels are kept within physiological concentrations [120]. They all seem to be dose-dependent and rarely occur when testosterone levels are kept within physiological concentrations [120].…”

“…Methyl testosterone capsules of 10 mg are not recommended since hepatic side effects have been reported [120]. This is a slow release preparation with great individual variations in absorption.…”