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Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone

Wood, Charles E. DVM, PhD; Lees, Cynthia J. DVM, PhD; Cline, J. Mark DVM, PhD

doi: 10.1097/gme.0b013e318191747a
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Objective: The goal of this pilot study was to evaluate the effects of testosterone (T) cotherapy on mammary gland and endometrial measures in a postmenopausal primate model.

Methods: Twenty-five surgically postmenopausal cynomolgus monkeys were randomized by social group to receive daily treatment with (1) placebo, (2) oral micronized 17β-estradiol (1 mg/d equivalent in women) + progesterone (200 mg/d equivalent in women) (E + P), or (3) E + P with T administered via subcutaneous pellets for 8 weeks at a high dose (15 mg) followed by 8 weeks at a low dose (1.5 mg) (E + P + T). The main outcome measures were breast and endometrial epithelial proliferation, as measured by Ki67/MIB1 immunolabeling.

Results: Intralobular breast proliferation did not differ significantly among groups after 8 weeks of treatment but was marginally higher (P = 0.03) in the E + P + T group after 16 weeks of treatment. No significant increase in proliferation was seen for E + P alone. Comparable changes in mammary gland markers of estrogen-receptor activity were seen for the E + P and E + P + T groups. In the endometrium, the addition of T did not increase endometrial glandular proliferation or estrogen-receptor activity or result in any distinct histologic changes.

Conclusions: The findings of this study do not support the idea that T antagonizes the effects of combined hormone therapy on breast proliferation or markers of estrogen-receptor activity. Overall, the short-term effects of T cotherapy on the mammary gland and endometrium were minimal.

The present study aimed to evaluate the effects of testosterone cotherapy on mammary gland and endometrial measures in a postmenopausal primate model. The results do not support the idea that testosterone antagonizes the effects of combined hormone therapy on breast proliferation or markers of estrogen-receptor activity and the short-term effects of testosterone cotherapy on the mammary gland and endometrium were minimal.

From the Section on Comparative Medicine, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC.

Received September 4, 2008; revised and accepted October 15, 2008.

The contents are solely the responsibility of the authors and do not necessarily represent the view of the National Center for Research Resources or the National Institutes of Health.

Funding/support: Funding for this work was provided by the Martin & Sharleen Cohen Foundation for Biomedical Research (J.M.C./C.E.W.) and the National Institutes of Health (National Center for Research Resources grant K01RR021322) (C.E.W.).

Financial disclosure: None reported.

Address correspondence to: Charles E. Wood, DVM, PhD, Section on Comparative Medicine, Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail: chwood@wfubmc.edu

©2009The North American Menopause Society