Influence of methyltestosterone postmenopausal therapy on plasma lipids, inflammatory factors, glucose metabolism and visceral fat: a randomized study

Abstract

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42-62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E 2 ) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E 2 , testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG ðP , 0:001Þ and increase in free testosterone index (P , 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group ðP , 0:05Þ, but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E 2 , for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.

Testosterone, SHBG and cardiovascular health in postmenopausal women

“…Experimental data suggest direct effects of testosterone on body composition, lipid levels and glucose metabolism. We postulate that increased androgenicity contributes to the accumulation of visceral fat and impairment of glucose metabolism, creating a vicious circle, whereby the increase in insulin and fat tissue in turn promote the production of 123 Surgical T Transdermal (patch) 300 mg per day 24 weeksBraunstein et al 124 Surgical T Transdermal (patch) 150/300/450 mg per day 24 weeksSimon et al 125 Surgical T Transdermal (patch) 300 mg per day 24 weeksDavis et al 126 Surgical T Transdermal (patch) 300 mg per day 24 weeksShifren et al 120 Natural T Transdermal (patch) 300 mg per day 24 weeksNathorst-Boost et al 127 Natural T Transdermal (gel) 10 mg per day 3 monthsBurger et al 128 Natural/surgical T Implant 50 mg  1 6 weeks -Davis et al 122 Natural/surgical T Implant 50 mg per 3 months 24 months k fat mass Farish et al 129 Surgical T Implant 100 mg  1 6 monthsHickok et al 130 -MT Oral 1.25 mg per day 6 months k HDL-C Watts et al 131 Surgical MT Oral 2.5 mg per day 24 months k HDL-C, triglycerides Basaria et al 132 Natural/surgical MT Oral 2.5 mg per day 16 weeks k HDL-C, triglycerides m fibrinogen Dobs et al 133 Natural/surgical MT Oral 2.5 mg per day 16 weeks k HDL-C, triglycerides, fat mass Lobo et al 134 Natural/surgical MT Oral 1.25 mg per day 16 weeks k HDL-C, triglycerides Warnock et al 135 Surgical MT Oral 1.25 mg per day 8 weeks k HDL-C, triglycerides Leao et al 136 Surgical MT Oral 1.25 mg per day 12 months k HDL-C m visceral fat mass Barrett-Connor et al 137 Surgical MT Oral 1.25 mg per day 24 months k HDL-C, triglycerides Raisz et al 138 Natural/surgical MT Oral 2.5 mg per day 9 weeks k HDL-C, triglycerides Penotti et al 139 Natural TU Oral 40 mg per day 8 months k HDL-C, m pulsatile index (PI)…”

“…An increase in lean body mass and decrease in fat mass have been reported after coadministration of methyltestosterone 133 and testosterone implants. 122 In contrast, Leao et al 136 described an increase in body weight and visceral fat mass after the addition of 1.25 mg methyltestosterone to transdermal estradiol therapy.…”

Benefits and risks of testosterone treatment for hypoactive sexual desire disorder in women: a critical review of studies published in the decades preceding and succeeding the advent of phosphodiesterase type 5 inhibitors

“…In contrast, Lellano et al (60) reported that testosterone provided cardiovascular protection, whereas other authors found neither an increased cardiovascular risk nor cardiovascular protection (61-63). Therefore, the effect of testosterone on the cardiovascular system remains inconclusive.…”

Cardiovascular Physiology of Androgens and Androgen Testosterone Therapy in Postmenopausal Women

“…It has also been noticed that free testosterone was not significantly corrected with triglycerides and HDL [52,55,56], the two lipids most frequently associated with the metabolic syndrome. A more recent study shows that combination of low-dose oral methyltestosterone and percutaneous oestradiol for 1 year only affects adversely HDL cholesterol and enhances visceral fat but does not result in significant increase of the components of metabolism syndrome, including glucose metabolism, other lipids, inflammatory markers or blood pressure [59].…”