A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women

Objective: To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women.Methods: This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with I g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire.Results: the EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. the EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses.Conclusions: EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. in general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.Wyeth, Collegeville, PAPREMARINWyeth Pharmaceut, Collegeville, PA USAMed Coll Georgia, Dept Obstet & Gynecol, Augusta, GA 30912 USAInst Saude & Ben Estar da Mulher, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynaecol, São Paulo, BrazilLoyola Univ Chicago, Dept Obstet & Gynaecol, Maywood, IL USAUniversidade Federal de São Paulo, Dept Gynaecol, São Paulo, BrazilWeb of Scienc

The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

<div><p>Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (<i>Egfr</i>) to be critical for endometrial function during early pregnancy. While ablation of <i>Her2</i> or <i>Erbb3</i> led to only a modest reduction in litter size, mice lacking <i>Egfr</i> expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place <i>Egfr</i> in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of <i>Egfr</i>, wingless-related MMTV integration site 4 (<i>Wnt4</i>) or boneless morphogenic protein 2 (<i>Bmp2</i>); revealing that not only are <i>Bmp2</i> and <i>Wnt4</i> key downstream effectors of <i>Egfr</i>, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that <i>EGFR</i> is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries <i>WNK1</i> and <i>AKT1S1</i>, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.</p></div