Effects of testosterone and estrogen treatment on the distribution of sex hormone receptors in the endometrium of postmenopausal women.
OBJECTIVE
Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of sex hormone receptors in glands and stroma of the endometrium of postmenopausal women.


METHODS
An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis.


RESULTS
At baseline, expressions of ER-alpha and progesterone receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone.


CONCLUSIONS
Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of sex hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.
Zang
Hong
H
Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden. hzang@hotmail.com
Sahlin
Lena
L
Masironi
Britt
B
Hirschberg
Angelica Lindén
AL
D000328:Adult; D004338:Drug Combinations; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology
D004338:Drug Combinations; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D013739:Testosterone; D004958:Estradiol; C010792:testosterone undecanoate