Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone.
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 17beta-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.
Wood
Charles E
CE
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA. chwood@wfubmc.edu
Lees
Cynthia J
CJ
Cline
J Mark
JM
D000284:Administration, Oral; D000728:Androgens / Q000008:administration & dosage*; D000818:Animals; D004336:Drug Antagonism; D016503:Drug Delivery Systems; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage; D004965:Estrogen Antagonists; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D008593:Menopause; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects; D013739:Testosterone / Q000008:administration & dosage*
D000728:Androgens; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol