Differential effects of selective estrogen receptor modulators on the vagina and its supportive tissues

Objective:Some selective estrogen receptor modulators (SERMs) have been associated with increased incidence of urinary incontinence and pelvic organ prolapse. This study explored the effects of five SERMs on the function and matrix components of the vagina and its supportive tissues.Methods:Fifty-six rats were administered SERMs by oral gavage for 8 weeks (n=8 for each SERM): raloxifene, tamoxifen, idoxifene, bazedoxifene at three different doses, and bazedoxifene with conjugated estrogens. Thirty-two rats were used as controls (n=8 per group): sham operation (no ovariectomy), ovariectomy only, ovariectomy with vehicle gavage, and 17-estradiol (subcutaneous). Vaginal supportive tissue complex was tested by uniaxial tensile testing. Total collagen content (hydroxyproline) and glycosaminoglycan content (Blyscan) were measured.Results:Ovariectomy significantly decreased the mechanical integrity of the vagina and its supportive tissue complex, with a decrease in ultimate load and stiffness (all P<0.05). Although 17-estradiol supplementation maintained these properties similarly to sham operation, none of the SERMs was as effectiveparticularly idoxifene, bazedoxifene at higher doses, and bazedoxifene with conjugated estrogens (all P<0.05). In addition, idoxifene and bazedoxifene induced increased total collagen content compared with sham or 17-estradiol treatment (all P<0.05). Glycosaminoglycan content did not change significantly.Conclusions:Unlike 17-estradiol, SERM supplementation does not fully prevent ovariectomy-induced deterioration in the biomechanical properties of the vagina and its supportive tissues, with the effects of idoxifene and bazedoxifene being the least. The paradoxically increased collagen content in these two groups may be related to increased formation of nonfunctional collagen.