Orkun Tan

Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: An up-to-date review

ObjectiveMenopause and its transition represent significant risk factors for the development of vulvovaginal atrophy-related sexual dysfunction. The objective of this study was to review the hormonal and nonhormonal therapies available for postmenopausal women with vulvovaginal atrophy-related sexual dysfunction, focusing on practical recommendations through a literature review of the most relevant publications in this field. MethodsThis study is a literature review. ResultsAvailable vaginal estrogen preparations are conjugated equine estrogens, estradiol vaginal cream, a sustained-release intravaginal estradiol ring, or a low-dose estradiol tablet. Vaginal estrogen preparations with the lowest systemic absorption rate may be preferred in women with history of breast cancer and severe vaginal atrophy. Vaginal lubricants and moisturizers applied on a regular basis have an efficacy comparable with that of local estrogen therapy and should be offered to women wishing to avoid the use of vaginal estrogens. ConclusionsOral, transdermal, or vaginal estrogen preparations are the most effective treatment options for vulvovaginal atrophy-related sexual dysfunction. Selective estrogen receptor modulators such as lasofoxifene and ospemifene showed a positive impact on vaginal tissue in postmenopausal women. Vaginal dehydroepiandrostenedione, vaginal testosterone, and tissue selective estrogen complexes are also emerging as promising new therapies; however, further studies are warranted to confirm their efficacy and safety.

The impact of bariatric surgery on obesity-related infertility and in vitro fertilization outcomes.

Obesity-related infertility is one of the most common problems of reproductive-age obese women who desire childbearing. The various types of bariatric surgeries have proved effective in controlling excessive weight gain, improving fertility, and preventing certain maternal and fetal complications in these women. This article summarizes the current evidence regarding the impact of bariatric surgery on obesity-related infertility and in vitro fertilization (IVF) outcomes. We have also attempted to draw conclusions about maternal and fetal risks and the benefits of bariatric surgery. Laparoscopic adjustable gastric banding and Roux-en-Y procedures are the two most commonly performed bariatric surgeries. Bariatric surgery was believed to improve menstrual irregularity and increase ovulation rate in anovulatory obese women, which lead to increased pregnancy rates. Although there are data in the literature suggesting the improvement of both the ovulatory function and the spontaneous pregnancy rates in obese women who lost weight after bariatric surgery, most of these are case-control studies with a small number of patients. The data are insufficient to determine an ideal time interval for pregnancy after bariatric surgery; however, the general consensus is that pregnancy should be delayed 12 to 18 months after bariatric surgery to avoid nutritional deficiencies. Few data exist regarding IVF success rates in women who have undergone bariatric surgery. One pairwise study discussed five patients who underwent bariatric surgery followed by IVF that resulted in three term pregnancies in three patients after the first IVF cycle. Many studies reported reductions in obesity-related pregnancy complications such as gestational diabetes and hypertensive disorders after bariatric surgery. Although data are inconsistent, some studies reported increased rate of preterm delivery and small for gestational age infants after bariatric surgery. Pregnancies after bariatric surgery may be considered high risk due to the concerns for vitamin deficiencies and gastrointestinal symptoms related to the surgery. Therefore the follow-up of these pregnancies might require a team approach including a maternal fetal medicine specialist, bariatric surgeon, and nutritionist.

Biochemistry, molecular biology and cell biology of gonadotropin-releasing hormone antagonists.

Purpose of review Gonadotropin-releasing hormone (GnRH) receptors are not only detected in the central nervous system but also in tissues such as ovary, endometrium, breast, gastrointestinal system, placenta and malignant tumors of ovary and breast. The direct role of GnRH-antagonists in ovarian function, implantation, cancer pathogenesis and treatment is under extensive investigation. This study reviews the biochemistry and molecular and cellular biology of GnRH-antagonists as well as GnRH types and their receptors. Recent findings The best clinical evidence with GnRH-antagonists has accumulated in controlled ovarian hyperstimulation protocols for prevention of premature luteinizing hormone surge (cetrorelix, ganirelix) and in the treatment of advanced-stage prostate cancer (abarelix and degarelix). GnRH–GnRH receptor pathways may have a role in the embryo implantation. The controversy still exists whether GnRH antagonist protocols result in slightly decreased clinical pregnancy rates compared with the GnRH agonist protocols. GnRH-antagonists could be used in the near future to treat some cancer types that express GnRH receptors. Summary GnRH-antagonists have various clinical applications in gynecology, reproductive medicine, urology and oncology. The emergence of well tolerated, orally active GnRH-antagonists may provide an alternative to long-term injections and is likely to have a major impact on the utility of GnRH analogues in the treatment of human diseases.

The extrapituitary effects of GnRH antagonists and their potential clinical implications: A narrated review

Potential roles of gonadotropin-releasing hormone (GnRH) antagonists on GnRH/GnRH receptor systems and their effects on the extrapituitary tissues are largely elusive. In this narrated review, we summarized the systemic effects of GnRH antagonists on ovary, endometrium, embryo implantation, placental development, fetal teratogenicity, reproductive tissue cancer cells, and heart while briefly reviewing the GnRH and GnRH receptor system. GnRH antagonists may have direct effects on ovarian granulosa cells. Data are conflicting regarding their effects on endometrial receptivity. The GnRH antagonists may potentially have detrimental effect on early placentation by decreasing the invasive ability of cytotrophoblasts if the exposure to them occurs during early pregnancy. The GnRH antagonists were not found to increase the rates of congenital malformations. Comparative clinical data are required to explore their systemic effects on various extrapituitary tissues such as on cardiac function in the long term as well as their potential use in other human cancers that express GnRH receptors.

Expression and activation of the membrane-cytoskeleton protein ezrin during the normal endometrial cycle

OBJECTIVE To examine total ezrin expression (ezrin and phospho-ezrin) through the normal endometrial cycle and to correlate ezrin activation and localization with cytologic changes. DESIGN Experimental laboratory study. SETTING University medical centers. PATIENT(S) Reproductive-age women. INTERVENTION(S) A total of 36 samples of normal early, mid-, and late proliferative- and secretory-phase endometrium were studied for immunoreactive total ezrin (ir-T-ezrin) and phospho-ezrin (ir-p-ezrin) expression by histology, immunohistochemistry, and Western blotting. MAIN OUTCOME MEASURE(S) Total ezrin and phospho-ezrin expressions through the normal endometrial cycle. RESULT(S) Throughout the cycle ir-T-ezrin is present in the epithelium. The intensity and localization of both ir-ezrin and ir-p-ezrin vary greatly throughout the cycle. The main findings include the following: lateral localization of ir-ezrin/ir-p-ezrin in association with membrane specializations; dense staining around secretory vacuoles (secretory phase); dense staining of the apical surfaces, including microvilli and pinopodes of epithelial cells, especially during the mid- to late secretory phases; and the presence of ezrin in the glandular secretions. Immunoreactive total ezrin and ir-p-ezrin were not expressed by stromal fibroblasts. CONCLUSION(S) Ezrin is a prominent protein in the cycling endometrium. The most striking findings were the gravitation of ir-ezrin/ir-p-ezrin to the periphery of secretory vacuoles, localization on apical surfaces of the luminal epithelium, dense ezrin staining in secretory-phase epithelial cell plumes, and the presence of ir-ezrin/ir-p-ezrin in secretory-phase luminal secretions. These findings may have functional implications, especially for implantation biology.

Estradiol Regulates Expression of Polysialated Neural Cell Adhesion Molecule by Human Vascular Endothelial Cells

Rationale: The mechanism of atherogenesis includes leukocyte adhesion to endothelial cells followed by migration into the subendothelial space. The polysialylated neural cell adhesion molecules (PSA-nCAMs) are a group of hydrophilic neural cell adhesion molecule (NCAM) isoforms that inhibit NCAM: NCAM association, thereby blocking cell: cell adhesion. During previous studies, we demonstrated that sialylation of specific NCAMs are upregulated at proestrus in the rat and that PSA-nCAM is expressed by the rat vascular endothelium. Methods and Results: In this study, we sought the presence of PSA-nCAM in human vessels and regulation of its expression in estradiol-treated human umbilical vascular endothelial cells (HUVEC). Immunoreactive PSA-nCAM (ir-PSA-nCAM) was shown in blood and lymph vessels of adult rats and human brain, skin, liver, lung, cervix, endometrium, and ovary. Staining for ir-PSA-nCAM was present on the glycocalyceal surface of estradiol-treated HUVEC, but not in the presence of the estrogen receptor (ER)-blocker fulvestrant. Western blotting confirmed these findings. Conclusions: PSA-nCAM is widely present in the glycocalyx of human and rat vascular endothelium. It also is expressed by HUVEC, in which it is induced by estradiol. The estrogen-regulated presence of vascular PSA-nCAM could diminish NCAM-dependent interactions between vessels and circulating leukocytes, thereby impeding vascular inflammation and atherogenesis, and, contributing to estrogen-induced cardioprotection. This hypothesized action is presently under study.