Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.

Introduction Vulvovaginal atrophy (VVA) is reported by one-quarter to one-half of postmenopausal women. Aim We evaluated the prevalence, inconvenience of, and issues surrounding hormone use for VVA symptoms in women who were current, past, and never users of menopausal hormone therapy (MHT), along with the relationship of sexual activity to VVA symptoms. Methods An online survey was sent to 3,471 women ≥45 years old participating in a panel of approximately 43,000 U.S. adults maintained by Knowledge Networks. Respondents were stratified by MHT use (current, past, and never) and sexual activity (sexually active and not sexually active). Final respondent data underwent a poststratification process and Chi-square analysis of hormone use and VVA by sexual activity. Main Outcome Measures Percent, calculated as the ratio of response over total responding for each survey question for all and stratified respondents. Results Forty-five percent (1,038/2,290) of respondents (age range 45–89 years; mean 60.7 years) were postmenopausal and currently or previously experienced VVA. Approximately 60% of past or never users of MHT reported vaginal symptoms; >90% found them bothersome. In comparison, 82% of current users reported VVA symptoms prior to use. 85% of all respondents were aware of safety issues associated with MHT. The prevalence and perceived severity of VVA symptoms were substantial but less frequent in nonsexually active women. Analysis of MHT use by past or current hormone use indicated a trend away from oral dosing and towards patch or vaginal hormones. Conclusions Postmenopausal women have a high rate of VVA symptoms. Those who use MHT do so for multiple reasons—hot flashes, VVA, bone protection, dyspareunia—and most have concerns about long-term safety, despite the fact that the majority of MHT use was for >5 years. Safety concerns and lack of physician recommendation were major reasons for not using or discontinuing MHT.

SUMMARYPregnancy is a challenge to the immune system, which not only has to protect the mother and the fetus from invading pathogens but to also maintain immunological tolerance against the fetus. However, the mechanisms inhibiting local immune responses in the maternal decidual tissue are poorly understood. We have studied decidual CD14 + macrophages, which may be important in the maintenance of a tolerance against the developing fetus. Decidual macrophages expressed HLA-DR, but lower levels of costimulatory molecule CD86 than peripheral blood CD14+ monocytes from pregnant and nonpregnant women. Decidual macrophages produced spontaneously high levels of interleukin-10. Our findings suggest that decidual macrophages could represent an inhibitory type of APCs. Supporting this conclusion indoleamine 2,3-dioxygenase (IDO), suggested to have an immunosuppressive role in pregnancy, was expressed in decidual macrophages. Furthermore, decidual macrophages were not able to differentiate into dendritic cells under the influence of IL-4 + GM-CSF. These results suggest an immunoinhibitory function of decidual macrophages at the maternal-fetal interface.

Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period. Such effects would be advantageous if ospemifene were found to be effective in the long-term prevention of osteoporosis.

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2-4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.

Dendritic cells (DC) are professional antigen-presenting cells with a unique capacity to initiate and regulate immune responses. Immature CD1a+ DC can be cultured from CD14+monocytes in the presence of interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor in vitro. Results of this study show that the nonsteroidal anti-estrogens toremifene and tamoxifen inhibit this differentiation. In the presence of anti-estrogens the cells lose CD14 expression, but remain CD1a− and clearly have less dendritic processes than immature DC. Functionally, anti-estrogen-treated cells are inferior to immature DC in inducing proliferation of allogeneic T cells and in producing IL-12 p70 protein after CD40 ligation. The expression of the costimulatory molecules CD80 and CD86 is differentially regulated by anti-estrogens during DC differentiation. Furthermore, anti-estrogens are also able to inhibit the terminal maturation of DC. By inhibiting the functional differentiation of DC, anti-estrogens may have a role in the treatment and prevention of autoimmune diseases.

Ospemifene, at the dose of 90 mg/day, was more estrogenic than raloxifene, as shown by changes in serum follicle-stimulating hormone and sex hormone-binding globulin levels. Neither agent stimulated endometrium, but in contrast to raloxifene, ospemifene had a clear estrogenic effect in the vagina. Further studies with ospemifene are needed in subjects with vaginal atrophy.

Ospemifene is a novel selective estrogen receptor modulator (SERM). Here we studied the effects of ospemifene on bone turnover in postmenopausal women. This was a randomized, double-blind study in which 159 healthy postmenopausal women received 30 (n = 40), 60 (n = 40) or 90 mg (n = 40) of ospemifene or placebo (n = 39) for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal crosslinking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring the levels of procollagen type I N propeptide (PINP), procollagen type I C propeptide (PICP), and bone-specific alkaline phosphatase (bone ALP) in serum. All markers were studied at baseline, 3 months, and 2-4 weeks after cessation of the medication. Ospemifene decreased bone resorption dose-dependently, as seen from falls in NTX by 6.1, 9.4 and 12.9% in the 30, 60 and 90 mg ospemifene groups, respectively (p < 0.05 for all dose levels when compared to placebo). CTX values decreased in the 90 mg ospemifene group by 4.8% (p < 0.05). A dose-dependent decrease was also observed in the bone formation markers: PINP values decreased by 9.8 (p < 0.05) and 15.3% (p < 0.01), and PICP values by 12.0 and 11.9% in the 60 and 90 mg ospemifene groups, respectively. Bone ALP decreased in 60 and 90 mg ospemifene groups by 1.9 and 2.6%, respectively (p < 0.05 for both dose levels when compared to placebo). These results show that ospemifene is effective in reducing bone turnover in postmenopausal women.