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ABSTRACT: The most recent meta-analysis appearing in Fertility and Sterility on acupuncture was reevaluated in view of the marked heterogeneity of interventions, controls, data analysis, and timing of interventions in the trials that were included. After removing some of the trials and data based on more rigorous standards for a high quality meta-analysis, a significant benefit of the intervention could no longer be shown. When studies with and without placebo controls were analyzed separately, a placebo effect was suggested. Individual trials with a confidence limit below unity emphasized the potential for a detrimental impact on outcomes, which should be considered both in using acupuncture clinically as an adjunct for IVF and in design of future trials. Much more data that includes a placebo control will be required before a conclusion can be made that acupuncture has a true treatment effect on IVF outcomes. However, unless the timing and method of the acupuncture are standardized, practitioners will still have difficulty being sure that their particular method will help beyond the apparent benefit provided by a placebo.
Fertility and sterility 01/2013; · 3.97 Impact Factor
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ABSTRACT: PURPOSE: To compare ovarian morphology in adolescent girls with and without polycystic ovary syndrome (PCOS) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 21 adolescent girls (age 12-18 years) without and 19 adolescents with PCOS (diagnosis based on excessive hair growth and irregular menstrual cycles) ovarian volume, antral follicle count (AFC) per ovary, and follicle size were evaluated. MRI was performed at 1.5 T or 3 T and axial or angled-axial single-shot echo-train spin echo images of 6 mm slice thickness were acquired. In a subset of subjects, 2-mm images were also obtained. PCOS and non-PCOS groups were compared using mixed affects regression. RESULTS: Mean AFC per ovary and ovarian volume were substantially greater in PCOS subjects compared to non-PCOS subjects. Mean follicle size was similar between groups. Follicles exceeding 10 mm were seen in 2/19 PCOS subjects versus 9/21 non-PCOS subjects. Consistently higher follicle counts were detected in images obtained at 2 mm compared to 6-mm slice thickness. CONCLUSION: In adolescence, MRI of the ovary reveals distinct differences between girls with and without PCOS. MRI may help evaluate young patients in whom transvaginal ultrasound is contraindicated. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Predicals, Inc.
Journal of Magnetic Resonance Imaging 01/2013; · 2.70 Impact Factor
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ABSTRACT: Breast cancer survivors (BCS) taking aromatase inhibitors (AIs) are at an increased risk for decreased bone density and fractures. Given the role vitamin D plays in bone metabolism, we examined the prevalence of and risk factors for vitamin D deficiency in a study of postmenopausal BCS on AIs.
We collected data on 391 postmenopausal women with stage I-III breast cancer on AI therapy. Vitamin D levels were measured by radioimmunoassay from patients' sera; deficiency was defined as a level < 30 ng/mL. Multivariate models were created to assess risk factors for deficiency.
The median vitamin D level was 35 ng/mL (range 6.78-93.15), and 35% of women were vitamin D deficient. When adjusting for age and vitamin D supplementation, minority participants were more likely to be vitamin D deficient than white women, (adjusted odds ratio [AOR] 2.18, 95% confidence interval [CI]1.22-3.89, p=0.009). Both overweight (AOR 3.05, 95% CI 1.72-5.41, p<0.001) and obese participants (AOR 3.21, 95% CI 1.79-5.78, p<0.001) had higher deficiency rates than did normal weight participants.
Hypovitaminosis D is common in BCS, and those who are nonwhite or overweight are at a higher risk of deficiency despite taking vitamin D supplements.
Journal of Women s Health 03/2012; 21(4):456-62. · 1.57 Impact Factor
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ABSTRACT: In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety.
A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI).
Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel.
Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study.
Contraception 11/2011; 84(5):525-32. · 2.72 Impact Factor
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ABSTRACT: Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA.
We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders.
Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001).
Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.
Breast cancer research: BCR 01/2011; 13(1):R8. · 5.24 Impact Factor
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ABSTRACT: In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway.
This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women.
We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women. Setting: The study was conducted in a General Clinical Research Center in an academic medical center.
Women with PCOS (age, 18-37 yr; n = 10) and normal ovulatory controls (age, 18-37 yr; n = 11) were recruited. Interventions: For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 μg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 μg of recombinant hCG. Main Outcome Measure(s): We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration.
In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women.
In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.
The Journal of clinical endocrinology and metabolism 01/2011; 96(4):1106-13. · 6.50 Impact Factor
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ABSTRACT: In breast cancer survivors, antral follicle count appears to provide data on ovarian function that are independent of antimullerian hormone, FSH, and inhibin B. Therefore, ultrasound appears to be a tool that may not only corroborate, but also add to the accuracy of hormone measures for determining ovarian function in breast cancer survivors.
Fertility and sterility 12/2010; 95(5):1857-9. · 3.97 Impact Factor
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ABSTRACT: Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes.
We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables.
In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen.
These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer.
Breast cancer research: BCR 05/2010; 12(3):R26. · 5.24 Impact Factor
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ABSTRACT: Hot flashes in breast cancer survivors (BCS) receiving adjuvant aromatase inhibitor (AI) therapy are common, but risk factors for these symptoms are ill-defined. This study tested if body size is associated with hot flashes in BCS on AI therapy. A cross-sectional study of postmenopausal BCS receiving adjuvant AI therapy was performed. The primary outcome was occurrence of patient-reported hot flashes. The primary exposures of interest were current body size and weight change since breast cancer diagnosis. Three hundred participants were enrolled at a mean age of 61 years (range 33-86) after an average AI exposure of 23 months (range 1 month-9 years). Fifty-nine percent reported hot flashes, 32% reported moderate to severe hot flashes, and 25% reported significant worsening of hot flashes since starting AI therapy. Sixty-one percent experienced weight maintenance (±10 lb), while 27% had weight gain (gained 10 lb or more), and 11% had weight loss (lost 10 lb or more). In multivariable analysis, weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1-4.4) and hot flash severity (OR 2.6, 95% CI 1.3-5.0) after adjusting for confounding. Current body size was not associated with hot flash occurrence, severity or change with AI therapy. In an outpatient BCS population on AI therapy, weight gain is a risk factor for hot flash occurrence. Women who gained at least 10 lb since breast cancer diagnosis were two times more likely to have hot flashes than women who maintained or lost weight. These results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population.
Breast Cancer Research and Treatment 02/2010; 124(1):205-11. · 4.43 Impact Factor
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ABSTRACT: In late reproductive-aged breast cancer survivors, there is a need for real-time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age-matched control women and determined the association between these hormones and postchemotherapy menstrual pattern.
Breast cancer patients (n = 127) with American Joint Committee on Cancer stage I to III disease who were premenopausal at diagnosis were enrolled postchemotherapy and observed. The primary endpoint was chemotherapy-related amenorrhea (CRA) (> or = 12 months of amenorrhea after chemotherapy). Matched pair analyses compared AMH, inhibin B, and follicle-stimulating hormone (FSH) levels between cancer and age-matched control subjects. Associations between hormones, CRA status, and change in CRA status over time were assessed.
The median age of the patients at chemotherapy was 43.2 years (range, 26.7-57.8 years). At enrollment, median follow-up since chemotherapy was 2.1 years, and 55% of subjects had CRA. Compared with age-matched controls, cancer subjects had significantly lower AMH (P = .004) and inhibin B (P < .001) and higher FSH (P < .001). AMH (P = .002) and inhibin B (P = .001) were found to be significantly associated with risk of CRA, even after controlling for FSH. AMH was significantly lower (P = .03) and FSH was significantly higher (P = .04) in menstruating subjects who developed subsequent CRA.
AMH and inhibin B are 2 additional measures of postchemotherapy ovarian function in late reproductive-aged breast cancer survivors. With further research and validation, these hormones may supplement limited current tools for assessing and predicting postchemotherapy ovarian function.
Cancer 11/2009; 116(3):592-9. · 4.77 Impact Factor
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ABSTRACT: This prospective cohort study tested whether the most common hereditary thrombophilia, factor V Leiden (FVL) mutation, is associated with nonpregnancy after IVF. Factor V Leiden mutation prevalence was very low (1.6%) and had a preliminarily positive association with pregnancy, suggesting that routine testing in a general IVF population for FVL mutation as a cause of IVF failure and infertility is not indicated.
Fertility and sterility 06/2009; 92(4):1256-9. · 3.97 Impact Factor
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ABSTRACT: To determine if genetic variation in chemotherapy metabolism are associated with risk of ovarian failure in breast cancer patients after adjuvant chemotherapy.
Prospective cohort study.
Comprehensive cancer center.
Early-stage breast cancer patients who were premenopausal at cancer diagnosis and treatment.
None.
Chemotherapy-related ovarian failure (CROF).
A total of 127 breast cancer subjects who were premenopausal at cancer diagnosis and underwent cyclophosphamide-based chemotherapy were genotyped for nine single-nucleotide polymorphisms (SNPs) in enzymes involved in cyclophosphamide activation (CYP3A4, CYP2B6, CYP3A5) and detoxification (GSTA1, GSTM1, GSTP1, GSTT1). Median age at chemotherapy was 43.2 years. Median follow-up after chemotherapy was 5.2 years. For the entire cohort, there was no significant association between CROF and SNPs. However, the association between CROF and SNPs was modified by age at chemotherapy. In subjects younger than 45 years old at chemotherapy, CYP3A4 *1B variants had significantly longer time to CROF than CYP3A4 *1A homozygotes in an adjusted multivariable Cox model. Age and tamoxifen use were also independently associated with CROF.
A common SNP in a cyclophosphamide drug-metabolizing enzyme appears to be related to ovarian failure after cyclophosphamide-based chemotherapy in young women with breast cancer. Larger prospective studies to validate these results should be directed toward women younger than 45 years of age at chemotherapy.
Fertility and sterility 05/2009; 94(2):645-54. · 3.97 Impact Factor
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ABSTRACT: This study evaluated whether genes involved in the metabolism of steroid hormones are associated with hormone levels or menopausal symptoms.
We used a population-based prospective sample of 436 African American (AA) and European American (EA) women who were premenopausal at enrollment and were followed longitudinally through menopause. We evaluated the relationship between steroid hormone metabolism genotypes at COMT, CYP1A2, CYP1B1, CYP3A4, CYP19, SULT1A1, and SULT1E1 with hormone levels and menopausal features.
In EA women, SULT1E1 variant carriers had lower levels of dehydroepiandrosterone sulfate, and SULT1A1 variant carriers had lower levels of estradiol, dehydroepiandrosterone sulfate, and testosterone compared with women who did not carry these variant alleles. In AA women, CYP1B1*3 genotypes were associated with hot flashes (odds ratio [OR], 0.62; 95% CI, 0.40-0.95). Interactions of CYP1A2 genotypes were associated with hot flashes across menopausal stage (P = 0.006). Interactions of CYP1B1*3 (P = 0.02) and CYP1B1*4 (P = 0.03) with menopausal stage were associated with depressive symptoms. In EA women, SULT1A1*3 was associated with depressive symptoms (OR, 0.53; 95% CI, 0.41-0.68) and hot flashes (OR, 2.08; 95% CI, 1.64-2.63). There were significant interactions between SULT1A1*3 and hot flashes (P < 0.001) and between SULT1A1*2 and depressive symptoms (P = 0.007) on menopausal stage, and there were race-specific effects of SULT1A1*2, SULT1A1*3, CYP1B1*3, and CYP3A4*1B on menopause.
Our results suggest that genotypes are associated with the occurrence of menopause-related symptoms or the timing of the menopausal transition.
Menopause (New York, N.Y.) 17(5):1026-34. · 3.08 Impact Factor
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ABSTRACT: these statistics, improvements in treat- ment have significantly increased the number of survivors over the past 25 years. 3 In women, the 5-year survival for all cancers has increased from 57% to 64% over the last quarter century, most notably for breast cancer, whose survival rate has increased from 75% to 90% in the same timeframe. 4 For childhood cancers, the 5-year survival rate for all cancers has improved from 68% to 81%, with the largest increases observed in hematologic cancers. 4 It is estimated that 1 in 1000 adults in their thirties is a survivor of child- hood cancer. 5 The increasing number of survivors has highlighted the need for clinicians to consider survivorship issues from early menopause to fer- tility preservation in the care of this population.
