Endometriosis is a common
estrogen-dependent disorder. Medical treatments currently consist of
progestins or
GnRH agonists; however, neither is fully effective and both entail significant side effects. Selective
estrogen receptor (ER) modulators (
SERM) have tissue-selective actions, acting as an ER agonist in some tissues and ER antagonist in others. The
SERM bazedoxifene (BZA) effectively antagonizes
estrogen-induced uterine endometrial stimulation without countering
estrogenic effects in bone or central nervous system. These properties make it an attractive candidate for use in the treatment of
endometriosis. Experimental
endometriosis was created in reproductive-age CD-1 mice. After 8 wk, 10 animals received i.p.
injections of BZA (3 mg/kg·d) for 8 wk, whereas 10 received vehicle control. Mice were killed, and implant size was assessed. The mean size of the implants
after treatment was 60 mm(2) in the control group and 21 mm(2) in the BZA treatment group (P = 0.03). Quantitative PCR and immunohistochemical analysis were used to determine the effect on endometrial gene expression.
PCNA, ERĪ±, and LIF
mRNA and
protein expression were significantly decreased in endometrium of the treated group.
Caspase 3 mRNA expression was increased. Expression of PR and Hoxa10 were not significantly altered by treatment. There was no evidence of ovarian enlargement or
cyst formation. Decreased
PCNA and ER expression demonstrated that the regression of
endometriosis likely involved decreased
estrogen-mediated cell proliferation. BZA may be an effective novel agent for the treatment of
endometriosis due to greater endometrial-specific
estrogen antagonism compared with other
SERM.