THE EFFECTS OF LOW-DOSE TESTOSTERONE TREATMENT ON LIPID-METABOLISM, CLOTTING FACTORS AND ULTRASONOGRAPHIC OVARIAN MORPHOLOGY IN WOMEN

INTRODUCTION Low doses of androgen are used in women for the symptomat ic treatment of sexual dysfunction and premenstrual syndrome (PMS). Ho wever, little is known about the long-term safety of androgen use in w omen. This study investigated the effects of low dose exogenous testos terone (T) on lipid metabolism, markers of activation of the coagulati on system and ultrasonographic ovarian morphology in women. PATIENTS T wenty-two patients with severe PMS (age 39.6 +/- 3.1 years, mean +/- S D) treated with subcutaneous T implants (100 mg six monthly) for at le ast two years (mean duration 3.3 (+/- 0.9 years) were compared with 22 age-matched (age 37.7 +/- 2.9 years) control patients with severe PMS who had not previously received T treatment. All women continued to h ave regular menses. MEASUREMENTS Fasting blood samples were obtained f or measurement of lipids and clotting factors and ovarian ultrasound e xamination carried out between days 1-4 of the menstrual cycle (2.3 +/ - 1.2 months after the T implant in T-treated group). RESULTS Mean pla sma T was 4.5 +/- 2.2 nmol/l, and 1.9+/-0.6 nmol/l in the treated and control groups, respectively. In the T-treated group apolipoprotein-A1 (Apo-Al) (treated 99.2 +/- 12 vs controls 116.2 +/- 27.7 g/l, P< 0.01 ) and high density lipoprotein cholesterol (HDL-C) (treated 1.3+/-0.3 vs controls 1.5 +/- 0.4 nmol/l, P< 0.01) were significantly decreased. In addition very low density lipoprotein cholesterol (VLDL-C) (treate d 0.4 +/- 0.3 vs controls 0.2 +/- 0.1 nmol/l, P< 0.05) was increased i n T-treated patients. There were no differences in total serum cholest erol and triglyceride or low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), lipoprotein(a), lecithin:cholesterol acyltra nsferase and cholesteryl ester transfer protein activity. There was no difference in clotting factors between the two groups which included prothrombin time, fibrinogen, antithrombin-III, protein-C, protein-S ( total and free), tissue plasminogen activator, plasminogen activator i nhibitor, beta-thromboglobulin and prothrombin fragments 1.2. Ultrasou nd showed normal ovarian architecture with no evidence of polycystic o varian changes in any patients in the T-treated group. No patient expe rienced adverse symptoms while on T treatment, in particular, there we re no complaints of hirsutism or acne and no one requested termination of treatment. CONCLUSION Low-dose testosterome administration to wome n for over two years did not induce changes in ovarian architecture bu t had small, potentially atherogenic effects on some parameters of lip id and lipoprotein metabolism. However, no differences were detected i n markers of activation of the clotting system to indicate an actual i ncrease in the risk of thrombosis. Overall, this study provides largel y reassuring data about the safety of low-dose androgen treatment in w omen. However, caution should be exercised in women with existing or a familial predisposition to lipid abnormalities, because of the small but significant changes found in HDL-C, ape-Al and VLDL-C.