Addressing the Needs of Transgender Patients: How Gynecologists Can Partner in Their Care.

IMPORTANCE: With the increase in patients who identify as transgender, it is crucial that gynecologists are culturally and clinically competent in understanding their unique needs. OBJECTIVE: The aim of this study was to identify the key gynecologic issues facing transgender patients and develop an overarching framework of tools needed to address these issues. EVIDENCE ACQUISITION: A review of the existing literature was undertaken to address the key clinical aspects of care. RESULTS: Various aspects of the gynecologic care of transgender patients, including health maintenance and cancer screening examinations, hormone replacement therapy, hysterectomy and salpingo-oophorectomy, and referral and collaboration with the patient's care team, are outlined. CONCLUSIONS AND RELEVANCE: Transgender patients are more likely to be engaged and seek care if their identity and their needs are understood. While many aspects of transgender health care follow standard practices, there are significant and important differences, including gender-affirming therapies. This article aims to give gynecologists the necessary tools to partner in the care of transgender patients.

The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women's Health Initiative Randomized Controlled Trial.

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.

Prospective analysis of association between statin use and breast cancer risk in the women's health initiative.

BACKGROUND: Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Women's Health Initiative (WHI) to assess the relationship between statins and breast cancer risk. METHODS: The population included 154,587 postmenopausal women ages 50 to 79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD, 3.3) years. Information on statins was collected at baseline and years one, three, six, and nine. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided. RESULTS: Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus nonusers was 0.94 (95% CI, 0.83-1.06). In the multivariable-adjusted, time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71-1.07). There was no significant trend by overall duration of use (P value for trend 0.68). There was no effect of tumor stage, grade, or hormone receptor status. CONCLUSION: Overall, statins were not associated with breast cancer risk. IMPACT: Our study is one of the largest prospective observational studies on this topic, and substantially adds to the literature suggesting no relationship between statins and breast cancer risk.

Chlamydia trachomatis antigens recognized in women with tubal factor infertility, normal fertility, and acute infection.

OBJECTIVE: To identify Chlamydia trachomatis antigens associated with tubal factor infertility and acute infection. METHODS: A C trachomatis proteome array was used to compare antibody profiles among women with tubal factor infertility, normal fertility, and acute C trachomatis infection. RESULTS: Thirteen immunodominant antigens reacted with 50% or more sera from all women (n=73). Six C trachomatis antigens were uniquely recognized in women with tubal factor infertility. Combining fragmentation of the six antigens with serum sample dilution, chlamydial antigens HSP60, CT376, CT557, and CT443 could discriminate between women with tubal factor infertility and women with normal fertility with a sensitivity of 63% (95% confidence interval [CI] 0.41-0.77) and specificity of 100% (95% CI 0.91-1), respectively. These antigens were designated as tubal factor infertility-associated antigens. However, these tubal factor antigens were unable to distinguish tubal factor infertility patients from those with acute infection. A combination of CT875 and CT147 distinguished women with acute infection from all other C trachomatis-exposed women with a detection sensitivity of 63% (95% CI 0.41-0.77) and specificity of 100% (95% CI 0.95-1), respectively. Thus, CT875 and CT147 were designated as acute infection-associated antigens. CONCLUSION: A sequential screening of antibodies against panels of C trachomatis antigens can be used to identify women with tubal factor infertility and acute C trachomatis infection. LEVEL OF EVIDENCE: II.

Increased expression of macrophage colony-stimulating factor and its receptor in patients with endometriosis.

OBJECTIVE: To investigate the expression and regulation of colony-stimulating factor 1 (CSF-1) and its receptor, C-FMS, in endometriosis. DESIGN: In vivo and vitro study. SETTING: University-based academic medical center. PATIENT(S): Reproductive-age women undergoing surgery for benign conditions. INTERVENTION(S): Peritoneal and endometrial tissue samples were obtained. MAIN OUTCOME MEASURE(S): CSF-1 and C-FMS expression. RESULT(S): Significantly higher CSF-1 levels were found in peritoneal fluid of patients with endometriosis compared with control subjects. Ectopic endometriotic tissue had 3.5-fold and 1.7-fold increases in CSF-1 and C-FMS expression, respectively, compared with eutopic tissue. Coculture of endometrial cells from either established cell lines or patient samples with peritoneal mesothelial cells (PMCs) led to increased expression of CSF-1 and C-FMS. A higher but nonsignificant increase in levels of C-FMS and CSF-1 was found in cocultures of endometrial epithelial cells from patients with endometriosis compared with those without endometriosis. CONCLUSION(S): Increased CSF-1 levels may contribute to endometriosis lesion formation and progression. Elevation in CSF-1 after coculture of endometrial cells with PMCs suggests that endometrial tissue may be a source of peritoneal CSF-1. Increased C-FMS expression in endometrial cells from women with endometriosis cocultured with PMCs suggests that endometrial tissue involved in lesion formation is highly responsive to CSF-1 signaling.

Serum beta human chorionic gonadotropin levels can inform outcome counseling after in vitro fertilization.

The predictive value of serum beta hCG level for fetal cardiac motion and pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET is a useful predictor of subsequent presence of fetal cardiac activity and live birth and may assist clinicians in counseling patients regarding their IVF outcome.

Genome-wide identification of Chlamydia trachomatis antigens associated with tubal factor infertility.

OBJECTIVE: To identify Chlamydia trachomatis antigens that can be used to differentially diagnose tubal factor infertility in comparison with previously reported heat shock protein 60. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Infertile women with and without tubal pathology diagnosed laparoscopically. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antibody responses to C. trachomatis in infertile women with or without tubal pathologies using a C. trachomatis genome-wide proteome array. RESULT(S): Comparison of the antibody profiles revealed 30 C. trachomatis antigens that were preferentially recognized in women with tubal factor infertility, with a detection sensitivity and specificity of 80.6% and 56.5%, respectively, 10 of which showed 100% specificity. A combination of CT443 and CT381 antigens yielded the highest detection sensitivity (67.7%) while maintaining 100% specificity. CONCLUSION(S): These findings have demonstrated that antibodies to CT443 and CT381, when used in combination, have higher sensitivity and specificity in predicting tubal factor infertility than other indicators for tubal factor infertility, such as heat shock protein 60 antibodies (35.5%, 100%) or hysterosalpingogram (65%, 83%). Using a panel of C. trachomatis antigens to serologically diagnose tubal factor infertility can save the patients from undertaking expensive and invasive procedures for determining tubal pathology and choosing treatment plans.

Localization of Chlamydia trachomatis hypothetical protein CT311 in host cell cytoplasm.

The chlamydia-specific hypothetical protein CT311 was detected both inside and outside of the chlamydial inclusions in Chlamydia trachomatis-infected cells. The extra-inclusion CT311 molecules were distributed in the host cell cytoplasm with a pattern similar to that of CPAF, a known Chlamydia-secreted protease. The detection of CT311 was specific since the anti-CT311 antibody labeling was only removed by absorption with CT311 but not CPAF fusion proteins. In addition, both anti-CT311 and anti-CPAF antibodies only detected their corresponding endogenous proteins without cross-reacting with each other or any other antigens in the whole cell lysates of C. trachomatis-infected cells. Although both CT311 and CPAF proteins were first detected 12 h after infection, localization of CT311 into host cell cytosol was delayed until 24 h while CPAF secretion into host cell cytosol was already obvious by 18 h after infection. The host cell cytosolic localization of CT311 was further confirmed in human primary cells. CT311 was predicted to contain an N-terminal secretion signal sequence and the CT311 signal sequence directed secretion of PhoA into bacterial periplasmic region in a heterologous assay system, suggesting that a sec-dependent pathway may play a role in the secretion of CT311 into host cell cytosol. This hypothesis is further supported by the observation that secretion of CT311 in Chlamydia-infected cells was blocked by a C16 compound known to inhibit signal peptidase I. These findings have provided important molecular information for further understanding the C. trachomatis pathogenic mechanisms.

In vitro fertilization outcomes in Hispanics versus non-Hispanic whites.

The in vitro fertilization (IVF) outcomes, including clinical intrauterine gestation rate and live birth rate, between Hispanic and non-Hispanic white women were compared, and there were no differences. Hispanics were more likely to have a diagnosis of tubal factor infertility, whereas non-Hispanic white women were more likely to have endometriosis as their infertility diagnosis.

Low-fat dietary pattern and change in body-composition traits in the Women's Health Initiative Dietary Modification Trial.

BACKGROUND: The Women's Health Initiative Dietary Modification (DM) Trial was a randomized controlled trial that compared the effects of a low-fat (≤20% of total energy) or a usual diet in relation to chronic disease risk in postmenopausal women. OBJECTIVE: We characterized long-term body-composition changes associated with the DM trial and potential modifiers of these associations. DESIGN: In the DM trial, 48,835 women aged 50-79 y were randomly assigned to intervention (40%) or comparison (60%) groups. We studied a subset with whole-body dual-energy X-ray absorptiometry scans at baseline and during follow-up. Changes in fat mass (FM), lean mass (LM), and percentage body fat between the intervention (n = 1580) and comparison (n = 2731) groups at years 1, 3, and 6 were compared. By using generalized estimating equations, we calculated overall differences between groups and tested for interactions with age, diabetes, race-ethnicity (white, black, and Hispanic), body mass index (BMI), and hormone therapy (HT). RESULTS: The intervention women experienced significantly greater reductions in percentage body fat, FM, and LM at years 1 and 3 than did women in the comparison group (all P < 0.05). At year 6, only the FM change was significantly different between groups. Overall, the intervention was associated with reductions in percentage body fat (-0.8%; 95% CI: -1.0%, -0.6%), FM (-1.1 kg; 95% CI: -1.3, -0.8 kg), and LM (-0.17 kg; 95% CI: -0.28, -0.06 kg) during follow-up (all P < 0.003). Intervention associations varied by race-ethnicity, BMI, diabetes, and HT and remained significant after adjustment for physical activity. CONCLUSION: This intervention was associated with modest long-term body-composition changes; the findings were more robust in years 1 and 3. This trial was registered at clinicaltrials.gov as NCT00000611.

Association of tubal factor infertility with elevated antibodies to Chlamydia trachomatis caseinolytic protease P.

OBJECTIVE: The objective of the study was to assess antibodies against Chlamydia trachomatis heat shock proteins (HSP) in patients with tubal factor infertility (TFI), infertility controls (IFC), and fertile controls (FC). HSPs assist organisms in surviving caustic environments such as heat. STUDY DESIGN: Twenty-one TFI, 15 IFC, and 29 FC patients were enrolled after laparoscopic tubal assessment. The titers of antibodies against C trachomatis organisms and 14 chlamydial HSPs were compared among the 3 groups. RESULTS: TFI patients developed significantly higher levels of antibodies against C trachomatis and specifically recognizing chlamydial HSP60 and caseinolytic protease (Clp) P, a subunit of the ATP-dependent Clp protease complex involved in the degradation of abnormal proteins. CONCLUSION: In addition to confirming high titers of antibodies against C trachomatis organisms and HSP60 in TFI patients, we identified a novel link of TFI with anti-ClpP antibodies. These findings may provide useful information for developing a noninvasive screening test for TFI and constructing subunit anti-C trachomatis vaccines.