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Effects of Testosterone Treatment on Endometrial Proliferation in Postmenopausal Women

Department of Woman and Child Health, Divisions of Obstetrics and Gynecology (H.Z., A.L.H.) and Reproductive Endocrinology (L.S., B.M.), and Department of Oncology–Pathology (E.E.), Division of Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden

Address all correspondence and requests for reprints to: Hong Zang, M.D., Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet, SE-171 76 Stockholm, Sweden. E-mail: hong.zang{at}ki.se.

Context: Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited.

Objective: Our aim was to compare the influence of treatment with testosterone and/or estrogen on endometrial proliferation in healthy postmenopausal women.

Design: This was an open, randomized clinical study with parallel comparison of the groups.

Setting: The study was conducted at a women’s health clinical research unit and a research laboratory at a university hospital.

Participants: Sixty-three women who had experienced natural menopause participated in this study.

Interventions: After random assignment, the participants were administered orally testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or both for 3 months.

Main Outcome Measures: Endometrial thickness was measured, and endometrial proliferation evaluated on the basis of histopathol-ogy and expression of Ki-67, a proliferation marker.

Results: Endometrial thickness was significantly increased by treatment with estrogen alone or in combination with testosterone but was unaltered by testosterone alone. Among the women receiving estrogen alone, the proportion exhibiting histopathology indicative of proliferation increased significantly to 50% (P < 0.05), there was a nonsignificant increase to 28% with the combined treatment, whereas testosterone alone had no effect at all. Expression of Ki-67 was up-regulated significantly in both glands and stroma (P < 0.05, respectively) in both estrogen treatment groups. However, the expression was significantly higher in stroma by estrogen treatment alone than after combined treatment (P < 0.05).

Conclusions: The short-term treatment with testosterone of postmenopausal women does not stimulate endometrial proliferation. In addition, testosterone appears to counteract endometrial proliferation induced by estrogen to a certain extent.

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