Mechanisms
Low-dose testosterone in women lowers HDL cholesterol without changing CETP activity (Clin Endocrinol 1998)
Original title: The effects of low-dose testosterone treatment on lipid metabolism, clotting factors and ultrasonographic ovarian morphology in women
Twenty-two women with severe premenstrual syndrome treated with subcutaneous testosterone implants for at least two years were compared with 22 age-matched untreated women with severe premenstrual syndrome to assess effects on lipid metabolism, clotting factors and ovarian morphology. Testosterone-treated women had significantly lower apolipoprotein A-I and HDL cholesterol and higher VLDL cholesterol than controls, but there were no differences in total cholesterol, triglyceride, LDL cholesterol, apolipoprotein B, lipoprotein(a), lecithin cholesterol acyltransferase activity, or cholesteryl ester transfer protein activity between groups. No differences in clotting factors or ovarian ultrasound findings were found, and no adverse symptoms were reported, indicating low-dose testosterone causes small, potentially atherogenic lipid changes without altering CETP activity or increasing thrombosis risk markers.
Original abstract
Introduction: Low doses of androgen are used in women for the symptomatic treatment of sexual dysfunction and premenstrual syndrome (PMS). However, little is known about the long-term safety of androgen use in women. This study investigated the effects of low dose exogenous testosterone (T) on lipid metabolism, markers of activation of the coagulation system and ultrasonographic ovarian morphology in women.
Patients: Twenty-two patients with severe PMS (age 39.6 +/- 3.1 years, mean +/- SD) treated with subcutaneous T implants (100 mg six monthly) for at least 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 have regular menses.
Measurements: Fasting blood samples were obtained for measurement of lipids and clotting factors and ovarian ultrasound examination 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 plasma 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-A1) (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) (treated 0.4 +/- 0.3 vs controls 0.2 +/- 0.1 nmol/l, P < 0.05) was increased in T-treated patients. There were no differences in total serum cholesterol and triglyceride or low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), lipoprotein(a), lecithin:cholesterol acyltransferase 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 inhibitor, beta-thromboglobulin and prothrombin fragments 1.2. Ultrasound showed normal ovarian architecture with no evidence of polycystic ovarian changes in any patients in the T-treated group. No patient experienced adverse symptoms while on T treatment, in particular, there were no complaints of hirsutism or acne and no one requested termination of treatment.
Conclusion: Low-dose testosterome administration to women for over two years did not induce changes in ovarian architecture but had small, potentially atherogenic effects on some parameters of lipid and lipoprotein metabolism. However, no differences were detected in markers of activation of the clotting system to indicate an actual increase in the risk of thrombosis. Overall, this study provides largely reassuring data about the safety of low-dose androgen treatment in women. 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, apo-A1 and VLDL-C.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.