- Email: [email protected]
The association of urinary phthalate monoester concentrations with measures of ovarian reserve among patients undergoing fertility treatments
were observed at final on-therapy evaluation for systolic (+3.24 vs +0.92 mm Hg) and diastolic blood pressure (+2.37 vs +1.01 mm Hg) and heart rate (+1.81 vs –0.15 bpm). Laboratory values of potential clinical importance were observed in 42% of the desvenlafaxine group (placebo, 35%). CONCLUSION: Desvenlafaxine 100 mg/d was generally safe and welltolerated in postmenopausal women with VMS, with an AE profile consistent with other serotonin-norepinephrine reuptake inhibitors. Supported by: Funded by Pfizer Inc.
O-14 Monday, October 17, 2011 05:45 AM HORMONE VARIATIONS ASSOCIATED WITH QUANTITATIVE FAT MEASURES IN THE MENOPAUSAL TRANSITION. S. Senapati, H. Lin, G. Pien, R. D. Schwab, E. Freeman, C. Gracia. Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: We have previously found that reproductive hormone levels are associated with body size, and the association between estradiol (E2) and body size varies over the menopausal transition. This study aims to delineate these relationships using quantitative measures of visceral (Visc) and subcutaneous (SC) fat. DESIGN: Cross-sectional assessment of reproductive hormones and fat measures in a subset of women in a longitudinal cohort study of the menopausal transition (Penn Ovarian Aging Study). MATERIALS AND METHODS: Early follicular hormones (FSH, E2, LH, DHEAS, Testosterone) and axial/sagittal T-1 weighted abdominal MRI images were obtained in 78 women. Fat volume (cm3) was quantified using validated software, Amira. Visc and SC fat values were divided into tertiles for analysis. Multivariable linear regression models compared hormone values between tertiles adjusting for race, age, and menopausal status. RESULTS: Mean age was 52.2 and mean BMI was 30.9kg/m2. 44% were African American, 30% were smokers, and 43% had education > high school. There was no difference in age, race or tobacco use among tertiles of Visc or SC fat. Menopausal status was associated with tertiles of SC fat but not Visc fat. In adjusted models, E2 was positively associated with Visc fat tertiles (geometric mean (GM) E2: Low 17.6, Mid 26.8, High 40.0, P¼0.02) while FSH was inversely associated with SC and Visc fat tertiles (SC GM: Low 82.2, Mid 78.9, High 50.0, P¼0.04; Visc GM: Low 90.5, Mid 65.2, High 55.2, P¼0.03). The association of E2 with Visc and SC fat tertiles varied by menopausal status (P¼<0.001). Before menopause, E2 is inversely associated with Visc fat; post-menopause, E2 is positively associated with Visc fat. Other hormones were not associated with fat measures. CONCLUSION: Estradiol is associated with quantitative measures of visceral fat and varies by menopausal status. This finding suggests that visceral fat may be an important mediator in hormone changes over the menopausal transition. Supported by: NIH R01-AG-12745, NIH R01-HL-085695.
O-15 Monday, October 17, 2011 06:00 PM A DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL ON THE EFFECTS OF A LICORICE EXTRACT ON MENOPAUSAL SYMPTOMS. M. B. Baker, M. Ciccone, M. Wilson, F. Stanczyk, D. Shoupe. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, University of Southern California, Los Angeles, CA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: A licorice-extract (licogen) exhibits phytoestrogenic activity that may provide an alternative to traditional hormonal therapy. There is a paucity of data on its clinical effectiveness in treating symptoms associated with the menopausal transition. The objective of this study was to assess the effectiveness of a licorice extract (licogen) on menopausal symptomatology. DESIGN: Double-Blind, Placebo Controlled Trial. MATERIALS AND METHODS: Symptomatic peri- and menopausal subjects were randomized to twelve months of placebo, licogen 50 mg, or licogen 100 mg. Fasting serum, ultrasound measurement of the endometrial thickness, vaginal pH and urinary assessment of N-telopeptide were obtained at these visits. Subjects completed daily diaries recording the number and severity of hot flushes, the number of nighttime awakenings and vaginal dryness. Generalized estimating equations used to compare differences between the groups.
FERTILITY & STERILITYÒ
RESULTS: 51 subjects were randomly assigned to placebo (n ¼ 10), licogen 50 mg (n ¼ 21), or licogen 100 mg (n ¼ 20). The mean age 50.8 yrs (SD 4.8 yrs), median FSH 53.0 mIU/ml (IQR, 19.7 - 66.5), median E2 12.8 pg/ml (IQR, 8.5 - 43.5). Endometrial thickness was not statistically different (P¼0.90). Vaginal pH, urinary N-telopeptide, and vaginal dryness showed a statistically significant treatment effect, however this was not statistically significantly different from placebo. Both treatment groups showed a statistically significant reduction in moderate hot flushes over time however this was not statistically different from placebo (P¼.17). CONCLUSION: These results indicate that use of licogen as an alternative to hormone therapy may help to improve moderate hot flushes and vaginal dryness and be a safe treatment for the endometrium. Further studies with a larger placebo group are indicated. Supported by: F & C Licorice Ltd.
ENVIRONMENT AND REPRODUCTION O-16 Monday, October 17, 2011 04:15 PM THE ASSOCIATION OF URINARY PHTHALATE MONOESTER CONCENTRATIONS WITH MEASURES OF OVARIAN RESERVE AMONG PATIENTS UNDERGOING FERTILITY TREATMENTS. I. Souter, K. W. Smith, I. Dimitriadis, M. G. Keller, J. C. Petrozza, R. Hauser. Obstetrics/Gynecology-Reproductive Endocrinology & Infertility Division, Massachusetts General Hospital-Harvard Medical School, Boston, MA; Environmental Health, Harvard School of Public Health, Boston, MA. OBJECTIVE: To determine the association of urinary phthalate metabolite concentrations with measures of ovarian reserve. DESIGN: Prospective cohort, 201 women undergoing fertility treatment. MATERIALS AND METHODS: Urinary concentrations of 7 phthalate (P) metabolites [mono(2-ethylhexyl)-P (MEHP), monobutyl-P (MBP), monoethyl-P (MEP), monobenzyl-P (MBzP), mono(2-ethyl-5-hydroxyhexyl)-P (MEHHP), mono(2-ethyl-5-oxohexyl)-P (MEOHP), and mono(2-ethyl-5-carboxypentyl)-P (MECPP)] were measured using solid-phase extraction, high performance liquid chromatography, isotope dilution tandem mass spectrometry. Transvaginal ultrasonography was used to determine the ovarian volume and antral follicle count (AFC). Day-3 FSH was measured in the serum. Poisson, linear, and logistic regression were used to evaluate the association of urinary specific-gravity (SG) adjusted phthalate concentrations with measures of ovarian reserve, adjusted for age. RESULTS: SG-MEHP was negatively associated with the number of follicles (p-trend: 0.03), with an average decrease of 21% (95%CI:37%,2%; P¼0.03) and 19% (95%CI:34%,1%; P¼0.04) in the number of follicles for the highest and middle tertiles of SG-MEHP, respectively, compared to the lowest one. SG-MEOHP and SG-MEP were also negatively associated with the number of follicles (p-trend: 0.1). The middle and highest tertiles of SG-MEHP were associated with an increased odds of an AFC<15 (OR: 3.2, 95%CI:1.2-8.6, and OR: 4.2, CI:1.5-12.4, respectively). Similarly, the highest tertile of SG-MEOHP was associated with an increased odds of AFC<15 (OR: 13.1, 95%CI:1.1-8.8). CONCLUSION: Phthalate metabolites were detected in urine from >70% of participating women. There was a trend of lower AFC with higher levels of phthalates (mainly DEHP metabolites). Based on animal data showing that some phthalates are endocrine disruptors through altered endogenous steroid hormone signaling, there is potential concern in humans of an accelerated follicle loss and reproductive aging. Supported by: NIEHS grants ES009718 & ES000002.
O-17 Monday, October 17, 2011 04:30 PM BISPHENOL A (BPA) CONFERS DIRECT GENOTOXICITY TO SPERM WITH INCREASED SPERM DNA FRAGMENTATION. D. H. Wu, Y.-K. Leung, M. A. Thomas, R. Maxwell, S.-M. Ho. Obstetrics and Gynecology, University of Cincinnati, Cincinnati, OH; Environmental Health, University of Cincinnati, Cincinnati, OH. OBJECTIVE: BPA is associated with disruptive effects on spermatogenesis and reproductive organ development in animals, but studies on direct effects of BPA on human sperm function are lacking. We previously reported increased sperm total motility and rapid progression in response to estrogenic compounds and aimed to investigate the in vitro effects on sperm DNA fragmentation induced by BPA and 17b-estradiol (E). DESIGN: Prospective Controlled Study.
S5
O-14 Monday, October 17, 2011 05:45 AM HORMONE VARIATIONS ASSOCIATED WITH QUANTITATIVE FAT MEASURES IN THE MENOPAUSAL TRANSITION. S. Senapati, H. Lin, G. Pien, R. D. Schwab, E. Freeman, C. Gracia. Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: We have previously found that reproductive hormone levels are associated with body size, and the association between estradiol (E2) and body size varies over the menopausal transition. This study aims to delineate these relationships using quantitative measures of visceral (Visc) and subcutaneous (SC) fat. DESIGN: Cross-sectional assessment of reproductive hormones and fat measures in a subset of women in a longitudinal cohort study of the menopausal transition (Penn Ovarian Aging Study). MATERIALS AND METHODS: Early follicular hormones (FSH, E2, LH, DHEAS, Testosterone) and axial/sagittal T-1 weighted abdominal MRI images were obtained in 78 women. Fat volume (cm3) was quantified using validated software, Amira. Visc and SC fat values were divided into tertiles for analysis. Multivariable linear regression models compared hormone values between tertiles adjusting for race, age, and menopausal status. RESULTS: Mean age was 52.2 and mean BMI was 30.9kg/m2. 44% were African American, 30% were smokers, and 43% had education > high school. There was no difference in age, race or tobacco use among tertiles of Visc or SC fat. Menopausal status was associated with tertiles of SC fat but not Visc fat. In adjusted models, E2 was positively associated with Visc fat tertiles (geometric mean (GM) E2: Low 17.6, Mid 26.8, High 40.0, P¼0.02) while FSH was inversely associated with SC and Visc fat tertiles (SC GM: Low 82.2, Mid 78.9, High 50.0, P¼0.04; Visc GM: Low 90.5, Mid 65.2, High 55.2, P¼0.03). The association of E2 with Visc and SC fat tertiles varied by menopausal status (P¼<0.001). Before menopause, E2 is inversely associated with Visc fat; post-menopause, E2 is positively associated with Visc fat. Other hormones were not associated with fat measures. CONCLUSION: Estradiol is associated with quantitative measures of visceral fat and varies by menopausal status. This finding suggests that visceral fat may be an important mediator in hormone changes over the menopausal transition. Supported by: NIH R01-AG-12745, NIH R01-HL-085695.
O-15 Monday, October 17, 2011 06:00 PM A DOUBLE-BLIND, PLACEBO CONTROLLED TRIAL ON THE EFFECTS OF A LICORICE EXTRACT ON MENOPAUSAL SYMPTOMS. M. B. Baker, M. Ciccone, M. Wilson, F. Stanczyk, D. Shoupe. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, University of Southern California, Los Angeles, CA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA. OBJECTIVE: A licorice-extract (licogen) exhibits phytoestrogenic activity that may provide an alternative to traditional hormonal therapy. There is a paucity of data on its clinical effectiveness in treating symptoms associated with the menopausal transition. The objective of this study was to assess the effectiveness of a licorice extract (licogen) on menopausal symptomatology. DESIGN: Double-Blind, Placebo Controlled Trial. MATERIALS AND METHODS: Symptomatic peri- and menopausal subjects were randomized to twelve months of placebo, licogen 50 mg, or licogen 100 mg. Fasting serum, ultrasound measurement of the endometrial thickness, vaginal pH and urinary assessment of N-telopeptide were obtained at these visits. Subjects completed daily diaries recording the number and severity of hot flushes, the number of nighttime awakenings and vaginal dryness. Generalized estimating equations used to compare differences between the groups.
FERTILITY & STERILITYÒ
RESULTS: 51 subjects were randomly assigned to placebo (n ¼ 10), licogen 50 mg (n ¼ 21), or licogen 100 mg (n ¼ 20). The mean age 50.8 yrs (SD 4.8 yrs), median FSH 53.0 mIU/ml (IQR, 19.7 - 66.5), median E2 12.8 pg/ml (IQR, 8.5 - 43.5). Endometrial thickness was not statistically different (P¼0.90). Vaginal pH, urinary N-telopeptide, and vaginal dryness showed a statistically significant treatment effect, however this was not statistically significantly different from placebo. Both treatment groups showed a statistically significant reduction in moderate hot flushes over time however this was not statistically different from placebo (P¼.17). CONCLUSION: These results indicate that use of licogen as an alternative to hormone therapy may help to improve moderate hot flushes and vaginal dryness and be a safe treatment for the endometrium. Further studies with a larger placebo group are indicated. Supported by: F & C Licorice Ltd.
ENVIRONMENT AND REPRODUCTION O-16 Monday, October 17, 2011 04:15 PM THE ASSOCIATION OF URINARY PHTHALATE MONOESTER CONCENTRATIONS WITH MEASURES OF OVARIAN RESERVE AMONG PATIENTS UNDERGOING FERTILITY TREATMENTS. I. Souter, K. W. Smith, I. Dimitriadis, M. G. Keller, J. C. Petrozza, R. Hauser. Obstetrics/Gynecology-Reproductive Endocrinology & Infertility Division, Massachusetts General Hospital-Harvard Medical School, Boston, MA; Environmental Health, Harvard School of Public Health, Boston, MA. OBJECTIVE: To determine the association of urinary phthalate metabolite concentrations with measures of ovarian reserve. DESIGN: Prospective cohort, 201 women undergoing fertility treatment. MATERIALS AND METHODS: Urinary concentrations of 7 phthalate (P) metabolites [mono(2-ethylhexyl)-P (MEHP), monobutyl-P (MBP), monoethyl-P (MEP), monobenzyl-P (MBzP), mono(2-ethyl-5-hydroxyhexyl)-P (MEHHP), mono(2-ethyl-5-oxohexyl)-P (MEOHP), and mono(2-ethyl-5-carboxypentyl)-P (MECPP)] were measured using solid-phase extraction, high performance liquid chromatography, isotope dilution tandem mass spectrometry. Transvaginal ultrasonography was used to determine the ovarian volume and antral follicle count (AFC). Day-3 FSH was measured in the serum. Poisson, linear, and logistic regression were used to evaluate the association of urinary specific-gravity (SG) adjusted phthalate concentrations with measures of ovarian reserve, adjusted for age. RESULTS: SG-MEHP was negatively associated with the number of follicles (p-trend: 0.03), with an average decrease of 21% (95%CI:37%,2%; P¼0.03) and 19% (95%CI:34%,1%; P¼0.04) in the number of follicles for the highest and middle tertiles of SG-MEHP, respectively, compared to the lowest one. SG-MEOHP and SG-MEP were also negatively associated with the number of follicles (p-trend: 0.1). The middle and highest tertiles of SG-MEHP were associated with an increased odds of an AFC<15 (OR: 3.2, 95%CI:1.2-8.6, and OR: 4.2, CI:1.5-12.4, respectively). Similarly, the highest tertile of SG-MEOHP was associated with an increased odds of AFC<15 (OR: 13.1, 95%CI:1.1-8.8). CONCLUSION: Phthalate metabolites were detected in urine from >70% of participating women. There was a trend of lower AFC with higher levels of phthalates (mainly DEHP metabolites). Based on animal data showing that some phthalates are endocrine disruptors through altered endogenous steroid hormone signaling, there is potential concern in humans of an accelerated follicle loss and reproductive aging. Supported by: NIEHS grants ES009718 & ES000002.
O-17 Monday, October 17, 2011 04:30 PM BISPHENOL A (BPA) CONFERS DIRECT GENOTOXICITY TO SPERM WITH INCREASED SPERM DNA FRAGMENTATION. D. H. Wu, Y.-K. Leung, M. A. Thomas, R. Maxwell, S.-M. Ho. Obstetrics and Gynecology, University of Cincinnati, Cincinnati, OH; Environmental Health, University of Cincinnati, Cincinnati, OH. OBJECTIVE: BPA is associated with disruptive effects on spermatogenesis and reproductive organ development in animals, but studies on direct effects of BPA on human sperm function are lacking. We previously reported increased sperm total motility and rapid progression in response to estrogenic compounds and aimed to investigate the in vitro effects on sperm DNA fragmentation induced by BPA and 17b-estradiol (E). DESIGN: Prospective Controlled Study.
S5