Vivian Lewis

Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding.

OBJECTIVE To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous combined therapy. DESIGN The Womens Health, Osteoporosis, Progestin, Estrogen (Womens HOPE) study, a randomized, double-blind, placebo-controlled trial. SETTING Study centers across the United States. PATIENT(S) Two thousand six hundred seventy-three healthy, postmenopausal women. INTERVENTION(S) Women received CEE, 0.625 mg/d; CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d, plus MPA, 1.5 mg/d; CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year. MAIN OUTCOME MEASURE(S) Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations. RESULT(S) Cumulative amenorrhea and no bleeding rates were higher with lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time since menopause and cumulative amenorrhea was observed (P<.05) in all CEE/MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients who experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05). CONCLUSION(S) Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.

Cortical and trabecular bone mineral content in women with endometriosis: effect of gonadotropin-releasing hormone agonist and danazol * †

Cortical bone (distal radius and ulna) and trabecular bone mineral content of the thoracolumbar vertebrae (T-12 to L-4) were measured with single-photon absorptiometry and quantitative computed tomography, respectively, in 55 women with laparoscopically staged endometriosis before, during, and after treatment with a gonadotropin-releasing hormone agonist (GnRH-a) or danazol. Mean pretreatment potassium phosphate mineral contents of T-12 to L-4 were 174 to 201 mg/ml in stage I to IV endometriosis and were within the 100 to 115th percentile of normal women. Similarly, cortical bone mineral contents were normal and were not significantly affected by either medication. Trabecular bone decreased significantly to 92.6 +/- 1.7% (n = 11, P less than 0.001) and 92.3 +/- 2.5% (n = 7, P less than 0.01) of baseline year after 6 months and 9 months of GnRH-a treatment and remained significantly depressed at 95.8 +/- 1.9% (P less than 0.0025) and 94.8 +/- 2.5% (P less than 0.005) 6 months after stopping treatment. Thus, cortical and trabecular bone mineral contents of women with endometriosis are normal, but treatment with GnRH-a induced significant loss of trabecular bone.

Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women

OBJECTIVE To evaluate the effect of bazedoxifene/conjugated estrogens (BZA/CE), a tissue selective estrogen complex, on uterine bleeding in postmenopausal women. DESIGN International, multicenter, randomized, double-blind, placebo- and active-controlled, phase III study (Selective estrogen Menopause And Response to Therapy [SMART]-1). SETTING Outpatient clinical. PATIENT(S) Healthy, postmenopausal women (N = 3,397) aged 40 to 75 years with an intact uterus. INTERVENTION(S) Daily oral therapy with BZA 10, 20, or 40 mg, each with CE 0.625 or 0.45 mg, raloxifene 60 mg, or placebo. MAIN OUTCOME MEASURE(S) Cumulative amenorrhea profiles and the incidence of bleeding or spotting over 2 years. RESULT(S) Treatment with BZA 20 or 40 mg with CE 0.625 or 0.45 mg was associated with rates of cumulative amenorrhea (>83% during cycles 1-13 and >93% during cycles 10-13) and bleeding or spotting that were comparable to those with placebo. Subjects who received BZA 10 mg/CE 0.625 mg experienced slightly lower cumulative amenorrhea rates throughout the study compared with placebo-treated subjects. CONCLUSION(S) Postmenopausal women treated with BZA 20 or 40 mg with CE 0.625 or 0.45 mg had high rates of cumulative amenorrhea that were similar to those reported with placebo. This new menopausal therapy may offer a favorable bleeding and tolerability profile.

Undertreatment of menopausal symptoms and novel options for comprehensive management

Abstract Objective: There is currently a gap in treatment options for menopausal symptoms and a need for comprehensive therapies that are safe and effective for postmenopausal women. This review discusses challenges in the management of menopausal symptoms and the effect of the Womens Health Initiative (WHI) study findings on current treatment patterns. It also examines present and future therapies. Research design and methods: A literature search was conducted using Medline, the Cochrane Database, and the National Heart Lung and Blood Institute WHI website with the following search terms: primary care, menopause, vasomotor symptoms, hormone therapy, osteoporosis, and vaginal atrophy. Searches were limited to articles published between 1995 and 2009. Results: Comprehensive therapies that target several aspects of menopause, such as vasomotor symptoms and chronic disease prevention, are currently hormone based. These hormone-based approaches are considered more effective than currently available nonhormonal therapies for the relief of menopausal symptoms. However, hormone therapy is not recommended for women at high risk for venous thromboembolic events, cardiovascular disease, and/or breast cancer. A need exists for novel therapies that mitigate menopausal symptoms, provide protection from osteoporosis, and encourage patient compliance without promoting cancer, heart disease, or stroke. Emerging modalities and strategies, such as the tissue selective estrogen complex (TSEC), Org 50081, MF101, and desvenlafaxine, may provide improved options for postmenopausal women. Conclusions: Several new menopausal therapies that may help to address the ongoing unmet need for safe and effective therapies for postmenopausal women are currently in development. In particular, the TSEC, which provides the benefits of both a selective estrogen receptor modulator and conjugated estrogens with an improved tolerability profile, may offer advantages over currently available treatment options. Limitations of this review include the narrow search criteria and limited search period.

Mitochondrial DNA integrity and copy number in sperm from infertile men

OBJECTIVE To determine the integrity and copy number of mitochondrial DNA (mtDNA) in spermatozoa from infertile men. We also compared mtDNA integrity to nuclear DNA integrity. DESIGN Observational. SETTING Tertiary care center. PATIENT(S) Semen samples were collected from 57 men, whose wives were undergoing in vitro fertilization, including 24 men with normal semen parameters. MAIN OUTCOME MEASURE(S) Quantitative long polymerase chain reaction (PCR) and real-time PCR were used to measure mtDNA integrity and copy number in spermatozoa. We also measured nuclear DNA integrity of spermatozoa with flow cytometry after acridine orange staining. RESULT(S) A significant increase in mtDNA copy number and a decrease in mtDNA integrity were observed in the spermatozoa samples from patients with abnormal semen parameters compared to the patients with normal semen parameters. The integrity and copy number of mtDNA were significantly correlated with sperm count. CONCLUSION(S) Mitochondrial DNA quantity and quality may serve as useful diagnostic markers of sperm quality in infertile men.

POLYCYSTIC OVARY SYNDROME A Diagnostic Challenge

Polycystic ovary syndrome remains a diagnostic challenge because there is no single defining test. The clinical presentation must dictate the extent of the work-up. The typical PCOS patient has a history of irregular menses and appears hirsute. Demonstration of ovulatory dysfunction and hyperandrogenism can also be made by appropriate hormonal measurements. An ultrasound showing multiple small ovarian follicles can support a diagnosis of PCOS in the patient for whom the clinical diagnosis has been made. Other causes of hyperandrogenism and ovulatory dysfunction should be excluded.

A prospective comparison of Synthetic Serum Substitute * and human serum albumin in culture for in vitro fertilization-embryo transfer †

OBJECTIVE To compare the efficacy of a globulin-containing protein source, Synthetic Serum Substitute (Irvine Scientific, Santa Ana, CA) and human serum albumin (HSA) in the early culture of human oocytes and embryos. DESIGN Oocytes from 31 consecutive IVF cycles were assigned alternately to dishes containing human tubal fluid (HTF) and either Synthetic Serum Substitute or HSA as the protein source. Each semen sample was split for processing in Synthetic Serum Substitute or HSA. Sperm processed in Synthetic Serum Substitute was added to oocytes cultured in Synthetic Serum Substitute, and sperm processed in HSA was added to oocytes cultured in HSA. After determination of fertilization, zygotes were placed in HTF containing the same protein supplement. Before transfer, the embryos were graded morphologically. MAIN OUTCOME MEASURES Occurrence of normal fertilization and embryo quality as assessed by morphological grading. RESULTS There was no significant difference in the occurrence of fertilization or in embryo morphological quality between oocytes cultured in Synthetic Serum Substitute as compared with HSA. CONCLUSIONS The use of a globulin-containing protein source in culture for IVF-ET did not improve the fertilization rate or embryo quality. Our design did not allow for demonstration of an effect on pregnancy rate.

Survey of genetic screening for oocyte donors

OBJECTIVE To describe current screening practices of oocyte donation programs in the Society for Assisted Reproductive Technologies (SART). DESIGN Descriptive data from a mailed questionnaire. SETTING Academic medical center. PARTICIPANT(S) In vitro fertilization programs in SART. INTERVENTION(S) Survey mailed to IVF programs in the SART registry. MAIN OUTCOME MEASURE(S) Current practices, opinions, and genetic criteria for oocyte donor selection. RESULT(S) Results from 159 of 229 (69%) eligible oocyte donation programs are described. Most centers (70%) completed fewer than 25 cycles and used both anonymous and directed donors. There was considerable variability in limits on numbers of cycles or births allowed per donor, with many centers having no limits. As well, the use of well-established screening tests for genetic disorders, such as sickle cell anemia and cystic fibrosis, varied considerably. Consultation with a geneticist was possible at most (89%) centers and specifically mentioned by some centers as a means to help make decisions. CONCLUSION(S) Most programs follow recommendations made by the American Society of Reproductive Medicine (ASRM) for screening of gamete donors, but a significant percentage does not use well-established testing. The widespread availability of genetic consultation should promote responsible screening practices.

A Sustainable Course in Research Mentoring

In this report, we describe a six‐year experience (2007‐2012) in a single CTSA awardee institution on the development, implementation and evaluation of a hybrid online mentoring curriculum that is applicable to CTSA trainees at various levels (graduate, medical students, and junior faculty) of career training. The curriculum offers convenience, engagement, and financial sustainability. Overall, we found high levels of satisfaction with the curriculum and mentoring experience among both protégés and mentors. Qualitative data showed remarkable consensus of 14 of the 15 domains of mentoring that form the framework of the mentoring curriculum: (1) accessibility, (2) selectivity, (3) engagement/support, (4) teaching/training, (5) clarity of performance/expectations, (6) sponsorship/sharing power judiciously, (7) demystifying the system (academia), (8) challenging/encouraging risk taking, (9) affirming, (10) providing exposure/visibility, (11) being an intentional role model, (12) protecting, (13) providing feedback, (14) self‐disclosure, and lastly (15) counseling, with the fifteenth domain “counseling” being the most controversial. Quantitative survey data of both mentors and protégés indicated a high degree of overall satisfaction in their mentor‐protégé dyad with 86% (59) of protégés and 86% (55) of mentors responding good or excellent to the “quality of time spent.” Mentors and protégés were most satisfied in the area of research, with 93% (62) of protégés and 96% (57) of mentors finding discussions in research very to somewhat useful for their own career advancement. Along with wide acceptability, this format is a useful option for institutions where face‐to‐face time is limited and education budgets are lean.

A randomized controlled trial of mentoring interventions for underrepresented minorities

Purpose To conduct a randomized controlled trial to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia. Method Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010 to 2013 into mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows, and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability. The primary analysis was a comparison of intervention effects on changes in protégés’ satisfaction of their basic psychological needs (competence, autonomy, and relatedness) with their mentor. They completed a well-validated, online questionnaire every two months for one year. Results There was no significant effect at the end of one year of either mentor training or peer mentoring on protégés’ psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés’ overall psychological need satisfaction with their mentor at two months, the time point closest to completing mentor training. Conclusions This randomized controlled trial showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study.