Effect of methyl testosterone administration on plasma viscosity in postmenopausal women.
BACKGROUND
Coronary heart disease (CHD) is the leading cause of mortality in women, with an incidence that increases after menopause, hence suggesting a cardioprotective role of oestrogen. Menopause also results in a decline in androgen levels with resulting symptoms of decreased libido and sexual dysfunction. Recently, there has been a growing interest in the treatment of postmenopausal women with androgens. However, no data are available on plasma viscosity and fibrinogen levels in postmenopausal women on combined oestrogen/androgen therapy.


METHODS
We conducted a randomized, double-blind, parallel-group 16-week study evaluating the effects of methyltestosterone supplementation on plasma viscosity and fibrinogen levels in postmenopausal women already on oestrogen replacement therapy (ERT) for at least 3 months. Women 21 years and older who were menopausal (natural or surgical) for at least 12 months were enrolled in the study. Participants were randomized to (1) an oestrogen-only group taking 1.25 mg esterified oestrogen (E-group) and (2) an oestrogen plus methyltestosterone (1.25 mg esterified oestrogen and 2.5 mg methyltestosterone) group (EA-group). Progesterone was not administered during the study period and women with intact uteri were given medroxyprogesterone 10 mg daily for 14 days at the completion of the study.


RESULTS
After 16 weeks of treatment, both groups had a significant increase in serum oestradiol levels from baseline. The levels of total oestrogen were significantly higher in the E-group compared to the EA-group (P < 0.001). There was a greater decrease in the LH and SHBG levels in the EA-group (P = 0.01). There was no difference in total testosterone; however, free testosterone levels were significantly higher in the EA-group (P = 0.01). At the end of the study, there was a significant decrease in plasma viscosity only in the EA-group (P = 0.01). Fibrinogen levels increased in both the groups, reaching significance only in the EA-group (P = 0.006). Baseline weight, body mass index (BMI) and the duration of menopausal status did not have any significant impact on the changes in plasma viscosity or fibrinogen. Women in the EA-group showed significant reductions in total cholesterol (P = 0.009), high density lipoprotein (HDL) (P < 0.001) and triglyceride (TG) levels (P = 0.001). There was no significant change in these parameters in the E-group.


CONCLUSIONS
This prospective study shows that the treatment of postmenopausal women on oestrogen with low-dose oral methyltestosterone results in a significant reduction in plasma viscosity. This lowering of plasma viscosity was achieved despite an increase in fibrinogen levels. Significant lowering of lipoproteins, especially TG levels, might have been responsible for this benefit. The combination regimen did not result in major side-effects. Based on these results, we feel confident in recommending low-dose androgens to postmenopausal women with a history of sexual dysfunction and decreased libido.
Basaria
Shehzad
S
Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Nguyen
Tam
T
Rosenson
Robert S
RS
Dobs
Adrian S
AS
D000368:Aged; D000704:Analysis of Variance; D001809:Blood Viscosity / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008525:Medroxyprogesterone / Q000627:therapeutic use; D008777:Methyltestosterone / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D045165:Testosterone Congeners / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
D008075:Lipoproteins, HDL; D012738:Sex Hormone-Binding Globulin; D045165:Testosterone Congeners; D014280:Triglycerides; D004958:Estradiol; D005340:Fibrinogen; D007986:Luteinizing Hormone; D002784:Cholesterol; D008525:Medroxyprogesterone; D008777:Methyltestosterone