title: Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone.
abstract: 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.
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA. chwood@wfubmc.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Lees
authors.forename: J Mark
authors.initials: JM
authors.lastname: Cline
mesh_terms: 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*
chemical_list: D000728:Androgens; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol