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The association of leptin levels, hormone levels and hot flashes in mid-life women
Monday, October 15, 2007 4:30 pm O-14 DOXYCYCLINE INHIBITS VASCULAR LEAKAGE AND PREVENTS OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN A MURINE MODEL. O. Fainaru, L. Bazinet, A. Adini, D’Amato R., M. D. Hornstein, J. Folkman. Vascular Biology Program, Department of Surgery, Children’s Hospital Boston and Harvard Medical School, Boston, MA; Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. OBJECTIVE: Gonadotropin-induced angiogenesis and capillary leakage play a key role in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Doxycycline has been reported to inhibit angiogenesis. Some angiogenesis inhibitors inhibit vascular leakage. We postulated that doxycycline would inhibit OHSS. DESIGN: Determining the effect of doxycycline on vascular leakage in a murine OHSS model. MATERIALS AND METHODS: OHSS was induced in 4 week old C57Bl/6 female mice. Pregnant mare serum gonadotropin (PMSG) was administered intraperitoneally (20 IU/day) for three days and on day 4, human chorionic gonadotropin (HCG) (5 IU) was injected to induce ovulation. For the Miles vascular permeability assay, mice were anesthetized 48 hours after HCG, and 0.1 ml of 5 mM Evans Blue dye was injected intravenously. After thirty minutes, the peritoneal cavity was infused with 2 ml of 0.9% NaCl. Subsequently, the fluid was extracted and Evans Blue concentration was measured spectrophotometrically at 620 nm. Designated groups of mice were treated during hormone stimulation with daily oral doxycycline (10–80 mg/kg/day). Ascites volume was determined spectrophotometrically using dye dilution. Ovaries were weighed, sectioned and stained with H&E for morphology and corpus luteum formation, and stained with anti-CD31 antibody for blood microvessel density. RESULTS: Doxycycline inhibited peritoneal vascular permeability 2.5 fold (0.126 0.069 vs. 0.311 0.163 OD 620 nm, P¼0.048) and ascites accumulation by 25% (307.9 35.0 mL vs. 399.2 16.6 mL, P¼0.046) in PMSG stimulated mice when compared to PMSG alone. Notably, doxycycline decreased vascular permeability to levels observed in non-stimulated mice (0.126 0.069 vs. 0.156 0.054 OD 620 nm, P¼0.46). Furthermore, doxycycline treatment did not inhibit ovarian stimulation or ovulation when compared to controls, as indicated by similar ovarian morphology, ovarian weights (25.7 5.4 mg vs. 25.1 2.5 mg, P¼0.83) and corpus luteum counts (12.7 3.2 vs.13.2 3.0, P¼0.81). Importantly, vessel density within the corpora lutea was similar in the two groups. CONCLUSIONS: Doxycycline effectively prevents OHSS in a murine model without compromising ovarian stimulation and consequent ovulation. This effect is most likely due to inhibition of vascular leakage. Its safety and implication in the prevention of human OHSS warrant further studies. Supported by: Fulbright and Rothschild foundations’ fellowships (O.F.). Department of Defense grant 76334–01 (J.F.).
Monday, October 15, 2007 4:45 pm O-15 LOCAL LUTEOTROPIC ROLE OF THE CORTICOTROPIN RELEASING HORMONE/UROCORTIN-RECEPTOR-BINDING PROTEIN (CRH/UCN-R-BP) SYSTEM IN THE PRIMATE CORPUS LUTEUM (CL). J. Xu, F. Xu, J. D. Hennebold, T. A. Molskness, R. L. Stouffer. Division of Neuroscience, and Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR. OBJECTIVE: We reported that components of the CRH/UCN-R-BP system are dynamically expressed in the primate ovary, particularly CL during the menstrual cycle. The ligands/Rs were mainly expressed at early luteal phase (LP), whereas BP expression was highest at late LP. DESIGN: In vivo study was designed to investigate the role of the CRH/ UCN-R-BP system in the ovulatory/luteinizing follicle of the primate ovary. MATERIALS AND METHODS: Either vehicle or 5 mg CRHR antagonist Astressin was injected into the preovulatory follicle (1day prior to luteinizing hormone surge) of monkeys (n ¼ 5) during the menstrual cycle. Ovaries were evaluated on day 3 post-injection for ovulation. Daily blood samples were analyzed for serum concentrations of progesterone (P) and estradiol (E) until
S6
Abstracts
menses. In subsequent treatment cycles, ovaries (n ¼ 3) bearing the injected follicles were removed on day 9 of the LP for histology. Nuclear DNA fragmentation was detected using the DeadEnd Colorimetric TUNEL System. RESULTS: All the control and Astressin-treated monkeys displayed typical stigmata on the ovary bearing the antecedent preovulatory follicle on day 3 post-injection. After the preovulatory surge, E levels declined by early LP in both groups. Thereafter, while increased in controls, the E levels of the Astressin-treated monkeys remained at baseline and were diminished (P<0.05) at midlate LP. P levels increased in both control and Astressintreated monkeys during the early LP. However, Astressin administration significantly (P<0.05) suppressed P levels during the mid-to-midlate LP compared to controls. All the control monkeys began menses on day 17 of the LP, whereas menstruation in Astressin-treated monkeys began on day 13 1.8 (P<0.05). On the day of ovariectomy, P levels were lower in Astressin-treated vs. control animals (2.3 0.4 vs. 4.6 0.3 ng/ml; P<0.05). There was an empty cavity lined by a single layer of fibroblastic cells in the CL following Astressin treatment, whereas control CL were filled with luteal cells. Unlike in controls, positive TUNEL staining was observed in large luteal cells (brown nuclei) and small cells (condensed fragmented nuclei; apoptotic cells) in the CL following Astressin treatment. CONCLUSIONS: The results of in vivo study are consistent with the hypothesis that activation of the CRH/UCN-R system in the primate CL promotes luteal development and/or structure-function and its loss is associated with luteal regression during the menstrual cycle. Supported by: The study was supported by NIH NICHD HD20869, HD42000,U54 HD 18185 and NCRR RR00163.
MENOPAUSE SIG ABSTRACTS Monday, October 15, 2007 3:00 pm O-16 THE ASSOCIATION OF LEPTIN LEVELS, HORMONE LEVELS AND HOT FLASHES IN MID-LIFE WOMEN. C. J. Alexander, C. Schilling, L. Gallicchio, J. A. Flaws, H. A. Zacur. Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD. OBJECTIVE: Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines, such as IL-1. When injected peripherally into rats, leptin induces significant dose-dependent increases in core body temperature. This study examined the associations between leptin levels and hot flashes, hormone levels and CYP genotypes in midlife women. DESIGN: Cross-sectional study. MATERIALS AND METHODS: Data were analyzed from a subset of women participating in a study on risk factors for menopausal symptoms among midlife women. To be eligible for this study, women had to be between the ages of 45 and 54 years, have intact ovaries and uterus, and report at least 3 menstrual periods in the last 12 months. Further, women could not be pregnant, have a history of cancer of the reproductive organs, or taking hormone replacement therapy, herbal supplements, or hormonal contraception. All women gave informed consent, completed a questionnaire, and donated a fasting blood sample. Blood samples were used to measure endogenous hormone levels and to genotype participants for polymorphisms in COMT, CYPc17, and CYP1B1. Of the 639 women who originally participated in the study, 200 women who were non-smokers and of Caucasian race had their blood samples assayed for leptin using ELISA kits. Among these women, correlation and regression methods were carried out to examine associations between leptin and hot flashes, hormone levels, and CYP genotypes. RESULTS: Leptin was associated with free estrogen index (P<0.0001), sex hormone binding globulin (SHBG) (P<0.0001), the duration of hot flashes (P¼0.02) and hot flashes experienced within the last 30 days (P¼0.02). As expected, leptin was highly correlated with BMI (r ¼ 0.75). Estradiol, estrone, testosterone, androstenedione and progesterone were not correlated to leptin when comparing women with and without hot flashes. Leptin levels were lower among current alcohol drinkers compared to former and never alcohol drinkers (P¼0.08). Leptin levels were not associated with the CYP genotypes in this study. CONCLUSIONS: In mid-life women, the data from this study suggest that leptin levels are associated with free estrogen index, SHBG levels and hot flashes. Genetic polymorphisms may be involved in the mechanism of hot
Vol. 88, Suppl 1, September 2007
flashes, as reported in our earlier studies, but were not associated with leptin levels. Alcohol use is not associated with leptin levels. Further studies are necessary to confirm these findings. Supported by: NIH Grant: R01AG018400.
Monday, October 15, 2007 3:15 pm O-17 BILATERAL OOPHORECTOMY AND DEPRESSION 12 MONTHS AFTER HYSTERECTOMY. J. Rohl, K. Kjerulff, J. Steege. Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC; Health Evaluation Sciences, Penn State Milton S. Hershey Medical Center, Hershey, PA. OBJECTIVE: This study was performed to assess the relationship between bilateral oophorectomy and depression after hysterectomy. DESIGN: The authors performed a secondary analysis of data collected from a cohort study of 1,299 women undergoing hysterectomy with or without concomitant oophorectomy in 49 Maryland hospitals between 1992– 1993. The data was previously collected for the Maryland Womens Health Study, a large prospective study designed to measure outcomes after hysterectomy for benign indications. MATERIALS AND METHODS: Women that were premenopausal by history at the time of surgery were included. The age range was 24–57 years of age. Oophorectomy status was based on abstracted data from the medical chart. Data on depression (defined as R2.6 on the Profile of Mood States scale) were collected at baseline (pre-surgical) and at 12-months follow-up. A complete case analysis was performed on 1,047 women. Bivariate analysis was performed using students t-test for continuous variables and Pearsons chi-square test for categorical variables. Binomial regression was used to obtain model estimates and confounding was assessed using backwards elimination. A sensitivity analysis was performed by running the final model after excluding women older than age 51. RESULTS: There were 614 women who were classified as not having bilateral oophorectomy and 433 women who were classified as having bilateral oophorectomy. Unadjusted bivariate analysis revealed that bilateral oophorectomy was associated with decreased risk of depression at 12 months post-operative: RR ¼ 0.59 (95% CI 0.42, 0.85). Stratified tabular analysis revealed that the effect of bilateral oophorectomy on depression varied depending on the presence of baseline depression: women with no baseline depression, RR ¼ 0.36 (95% CI 0.18, 0.69) and women with baseline depression, RR ¼ 0.87 (95% CI 0.59, 1.30). After adjusting for age, race, parity, income, diagnosis of endometriosis, and current smoking status, bilateral oophorectomy decreased the risk of depression in women without baseline depression [RR ¼ 0.36 (95% CI 0.17, 0.78)] but did not significantly affect those with baseline depression [RR 1.21 (95% CI 0.73, 2.00)]. The results of the sensitivity analysis showed similar risk ratios. CONCLUSIONS: Bilateral oophorectomy does not increase the risk of post-operative depression in women undergoing hysterectomy. Baseline depression, however, attenuates this effect. Improved mood most likely represents relief from symptoms for which surgical intervention is indicated. Supported by: None.
Monday, October 15, 2007 3:30 pm O-18 IS ANTRAL FOLLICLE COUNT (AFC) A GENETIC TRAIT? PREDICTIVE ABILITY OF MOTHER’S MENOPAUSAL AGE. S. J. Gillham, A. E. Modan, A. Mancuso, M. P. Rosen, M. I. Cedars. OB/GYN, University of California, San Francisco, San Francisco, CA. OBJECTIVE: Several studies have affirmed that at least 50% of the individual variability in menopausal age is genetically determined (Murabito, 2005) and, therefore, women with family histories of early menopause are, themselves, at increased risk for early menopause and early reproductive failure (Tibiletti, 1999). The objective of this study is to determine the relationship between maternal age at menopause and a patient’s current antral follicle count (AFC). DESIGN: Cross-sectional survey.
FERTILITY & STERILITYÒ
MATERIALS AND METHODS: Data was analyzed on 106 women, of reproductive age (19–47 years), who were seeking infertility treatment. Data included each participant’s age, BMI, ethnicity, medical and surgical diagnoses, AFC (determined by 5–7 mHz trans-vaginal ultrasound), and mother’s age at menopause (as reported by the subjects). Subjects with medical histories that affected ovarian volume or AFC, including endometriosis and ovarian surgery, were excluded. Multiple linear regression analysis, controlling for the subjects’ age, was performed to determine if the maternal age at menopause was associated with AFC in the daughter. RESULTS: The multivariate model suggests that the menopausal age of the mother is associated with the daughter’s AFC (Coeff ¼ 0.630, P<0.001, 95% CI 0.319, 0.951). In addition, this model suggests that for every year a patient ages, antral follicle count declines, in a linear fashion, by 0.65 follicles on average. TABLE 1.
AFC Total Age of Maternal Menopause Year
Coefficient
P-value
95% CI
0.630
<0.001
0.319
0.951
0.650
<0.001
0.937
0.362
CONCLUSIONS: AFC has increasingly been used as a predictor of stimulation response in fertility treatment (Bansci, 2002). Our data indicate that since the maternal age of menopause is directly related to the AFC in the daughter, that AFC itself may be a genetic trait. Therefore, these results support the role of AFC as a predictor of time to, and age of, menopause. Supported by: NIH/NICHD/NIA R01 HD044876, Cedars (PI).
Monday, October 15, 2007 3:45 pm O-19 DOES BODY SIZE AFFECT MEASURES OF OVARIAN RESERVE IN LATE REPRODUCTIVE AGE WOMEN? I. H. Su, C. R. Gracia, M. D. Sammel, H. Lin, E. W. Freeman. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA; Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Research on Reproduction and Women’s Health, University of Pennsylvania School of Medicine, Philadelphia, PA; Departments of Obstetrics and Gynecology and Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA. OBJECTIVE: We have reported that anti-mullerian hormone (AMH) and inhibin B are decreased in obese women in late reproductive years. The study objectives were to explore the association between obesity and antral follicle count (AFC) and to further examine the association between obesity and hormonal markers of ovarian reserve. DESIGN: Cross-sectional. MATERIALS AND METHODS: Thirty-six healthy, late reproductive age women were recruited in a 1:1 ratio of normal weight (BMI<25) to obese women (BMI>30). All had regular menstrual cycles (q22–35), an intact uterus, both ovaries, and no hormone use. Subjects underwent a blood draw, anthropometric measurements and a transvaginal ultrasound in the first 4 days of a cycle. Blood was assayed for AMH, inhibin B, estradiol and follicle stimulating hormone (FSH). Body mass index (BMI), ovarian volume and AFC were recorded. A priori size calculations were conducted to detect a two-fold increase in the proportion of obese subjects with low AFC (<4) with 80% power. Bivariable analyses assessed the association between obesity, demographic variables, AFC, ovarian volume and hormone measures. Separate multivariable linear regression models were developed for AMH and inhibin B. RESULTS: Mean age was 45 (95% CI 41–49). Mean BMI (95% CI) was 22.4 (21.6–23.2) for normal weight and 37.6 (34.2–40.8) for obese subjects. Mean AFC (95% CI) was 7.6 (5–10.2) for lean and 6.3 (3.3–9.3) for obese subjects (P¼0.35). Proportions of normal weight (17%) vs. obese subjects (22%) with AFC less than 4 were similar (P¼0.8). Ovarian volumes did not differ by body size. AMH levels in obese women were 72% lower on average than in lean women, after adjusting for age, AFC, smoking and race
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Monday, October 15, 2007 4:45 pm O-15 LOCAL LUTEOTROPIC ROLE OF THE CORTICOTROPIN RELEASING HORMONE/UROCORTIN-RECEPTOR-BINDING PROTEIN (CRH/UCN-R-BP) SYSTEM IN THE PRIMATE CORPUS LUTEUM (CL). J. Xu, F. Xu, J. D. Hennebold, T. A. Molskness, R. L. Stouffer. Division of Neuroscience, and Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR. OBJECTIVE: We reported that components of the CRH/UCN-R-BP system are dynamically expressed in the primate ovary, particularly CL during the menstrual cycle. The ligands/Rs were mainly expressed at early luteal phase (LP), whereas BP expression was highest at late LP. DESIGN: In vivo study was designed to investigate the role of the CRH/ UCN-R-BP system in the ovulatory/luteinizing follicle of the primate ovary. MATERIALS AND METHODS: Either vehicle or 5 mg CRHR antagonist Astressin was injected into the preovulatory follicle (1day prior to luteinizing hormone surge) of monkeys (n ¼ 5) during the menstrual cycle. Ovaries were evaluated on day 3 post-injection for ovulation. Daily blood samples were analyzed for serum concentrations of progesterone (P) and estradiol (E) until
S6
Abstracts
menses. In subsequent treatment cycles, ovaries (n ¼ 3) bearing the injected follicles were removed on day 9 of the LP for histology. Nuclear DNA fragmentation was detected using the DeadEnd Colorimetric TUNEL System. RESULTS: All the control and Astressin-treated monkeys displayed typical stigmata on the ovary bearing the antecedent preovulatory follicle on day 3 post-injection. After the preovulatory surge, E levels declined by early LP in both groups. Thereafter, while increased in controls, the E levels of the Astressin-treated monkeys remained at baseline and were diminished (P<0.05) at midlate LP. P levels increased in both control and Astressintreated monkeys during the early LP. However, Astressin administration significantly (P<0.05) suppressed P levels during the mid-to-midlate LP compared to controls. All the control monkeys began menses on day 17 of the LP, whereas menstruation in Astressin-treated monkeys began on day 13 1.8 (P<0.05). On the day of ovariectomy, P levels were lower in Astressin-treated vs. control animals (2.3 0.4 vs. 4.6 0.3 ng/ml; P<0.05). There was an empty cavity lined by a single layer of fibroblastic cells in the CL following Astressin treatment, whereas control CL were filled with luteal cells. Unlike in controls, positive TUNEL staining was observed in large luteal cells (brown nuclei) and small cells (condensed fragmented nuclei; apoptotic cells) in the CL following Astressin treatment. CONCLUSIONS: The results of in vivo study are consistent with the hypothesis that activation of the CRH/UCN-R system in the primate CL promotes luteal development and/or structure-function and its loss is associated with luteal regression during the menstrual cycle. Supported by: The study was supported by NIH NICHD HD20869, HD42000,U54 HD 18185 and NCRR RR00163.
MENOPAUSE SIG ABSTRACTS Monday, October 15, 2007 3:00 pm O-16 THE ASSOCIATION OF LEPTIN LEVELS, HORMONE LEVELS AND HOT FLASHES IN MID-LIFE WOMEN. C. J. Alexander, C. Schilling, L. Gallicchio, J. A. Flaws, H. A. Zacur. Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD. OBJECTIVE: Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines, such as IL-1. When injected peripherally into rats, leptin induces significant dose-dependent increases in core body temperature. This study examined the associations between leptin levels and hot flashes, hormone levels and CYP genotypes in midlife women. DESIGN: Cross-sectional study. MATERIALS AND METHODS: Data were analyzed from a subset of women participating in a study on risk factors for menopausal symptoms among midlife women. To be eligible for this study, women had to be between the ages of 45 and 54 years, have intact ovaries and uterus, and report at least 3 menstrual periods in the last 12 months. Further, women could not be pregnant, have a history of cancer of the reproductive organs, or taking hormone replacement therapy, herbal supplements, or hormonal contraception. All women gave informed consent, completed a questionnaire, and donated a fasting blood sample. Blood samples were used to measure endogenous hormone levels and to genotype participants for polymorphisms in COMT, CYPc17, and CYP1B1. Of the 639 women who originally participated in the study, 200 women who were non-smokers and of Caucasian race had their blood samples assayed for leptin using ELISA kits. Among these women, correlation and regression methods were carried out to examine associations between leptin and hot flashes, hormone levels, and CYP genotypes. RESULTS: Leptin was associated with free estrogen index (P<0.0001), sex hormone binding globulin (SHBG) (P<0.0001), the duration of hot flashes (P¼0.02) and hot flashes experienced within the last 30 days (P¼0.02). As expected, leptin was highly correlated with BMI (r ¼ 0.75). Estradiol, estrone, testosterone, androstenedione and progesterone were not correlated to leptin when comparing women with and without hot flashes. Leptin levels were lower among current alcohol drinkers compared to former and never alcohol drinkers (P¼0.08). Leptin levels were not associated with the CYP genotypes in this study. CONCLUSIONS: In mid-life women, the data from this study suggest that leptin levels are associated with free estrogen index, SHBG levels and hot flashes. Genetic polymorphisms may be involved in the mechanism of hot
Vol. 88, Suppl 1, September 2007
flashes, as reported in our earlier studies, but were not associated with leptin levels. Alcohol use is not associated with leptin levels. Further studies are necessary to confirm these findings. Supported by: NIH Grant: R01AG018400.
Monday, October 15, 2007 3:15 pm O-17 BILATERAL OOPHORECTOMY AND DEPRESSION 12 MONTHS AFTER HYSTERECTOMY. J. Rohl, K. Kjerulff, J. Steege. Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC; Health Evaluation Sciences, Penn State Milton S. Hershey Medical Center, Hershey, PA. OBJECTIVE: This study was performed to assess the relationship between bilateral oophorectomy and depression after hysterectomy. DESIGN: The authors performed a secondary analysis of data collected from a cohort study of 1,299 women undergoing hysterectomy with or without concomitant oophorectomy in 49 Maryland hospitals between 1992– 1993. The data was previously collected for the Maryland Womens Health Study, a large prospective study designed to measure outcomes after hysterectomy for benign indications. MATERIALS AND METHODS: Women that were premenopausal by history at the time of surgery were included. The age range was 24–57 years of age. Oophorectomy status was based on abstracted data from the medical chart. Data on depression (defined as R2.6 on the Profile of Mood States scale) were collected at baseline (pre-surgical) and at 12-months follow-up. A complete case analysis was performed on 1,047 women. Bivariate analysis was performed using students t-test for continuous variables and Pearsons chi-square test for categorical variables. Binomial regression was used to obtain model estimates and confounding was assessed using backwards elimination. A sensitivity analysis was performed by running the final model after excluding women older than age 51. RESULTS: There were 614 women who were classified as not having bilateral oophorectomy and 433 women who were classified as having bilateral oophorectomy. Unadjusted bivariate analysis revealed that bilateral oophorectomy was associated with decreased risk of depression at 12 months post-operative: RR ¼ 0.59 (95% CI 0.42, 0.85). Stratified tabular analysis revealed that the effect of bilateral oophorectomy on depression varied depending on the presence of baseline depression: women with no baseline depression, RR ¼ 0.36 (95% CI 0.18, 0.69) and women with baseline depression, RR ¼ 0.87 (95% CI 0.59, 1.30). After adjusting for age, race, parity, income, diagnosis of endometriosis, and current smoking status, bilateral oophorectomy decreased the risk of depression in women without baseline depression [RR ¼ 0.36 (95% CI 0.17, 0.78)] but did not significantly affect those with baseline depression [RR 1.21 (95% CI 0.73, 2.00)]. The results of the sensitivity analysis showed similar risk ratios. CONCLUSIONS: Bilateral oophorectomy does not increase the risk of post-operative depression in women undergoing hysterectomy. Baseline depression, however, attenuates this effect. Improved mood most likely represents relief from symptoms for which surgical intervention is indicated. Supported by: None.
Monday, October 15, 2007 3:30 pm O-18 IS ANTRAL FOLLICLE COUNT (AFC) A GENETIC TRAIT? PREDICTIVE ABILITY OF MOTHER’S MENOPAUSAL AGE. S. J. Gillham, A. E. Modan, A. Mancuso, M. P. Rosen, M. I. Cedars. OB/GYN, University of California, San Francisco, San Francisco, CA. OBJECTIVE: Several studies have affirmed that at least 50% of the individual variability in menopausal age is genetically determined (Murabito, 2005) and, therefore, women with family histories of early menopause are, themselves, at increased risk for early menopause and early reproductive failure (Tibiletti, 1999). The objective of this study is to determine the relationship between maternal age at menopause and a patient’s current antral follicle count (AFC). DESIGN: Cross-sectional survey.
FERTILITY & STERILITYÒ
MATERIALS AND METHODS: Data was analyzed on 106 women, of reproductive age (19–47 years), who were seeking infertility treatment. Data included each participant’s age, BMI, ethnicity, medical and surgical diagnoses, AFC (determined by 5–7 mHz trans-vaginal ultrasound), and mother’s age at menopause (as reported by the subjects). Subjects with medical histories that affected ovarian volume or AFC, including endometriosis and ovarian surgery, were excluded. Multiple linear regression analysis, controlling for the subjects’ age, was performed to determine if the maternal age at menopause was associated with AFC in the daughter. RESULTS: The multivariate model suggests that the menopausal age of the mother is associated with the daughter’s AFC (Coeff ¼ 0.630, P<0.001, 95% CI 0.319, 0.951). In addition, this model suggests that for every year a patient ages, antral follicle count declines, in a linear fashion, by 0.65 follicles on average. TABLE 1.
AFC Total Age of Maternal Menopause Year
Coefficient
P-value
95% CI
0.630
<0.001
0.319
0.951
0.650
<0.001
0.937
0.362
CONCLUSIONS: AFC has increasingly been used as a predictor of stimulation response in fertility treatment (Bansci, 2002). Our data indicate that since the maternal age of menopause is directly related to the AFC in the daughter, that AFC itself may be a genetic trait. Therefore, these results support the role of AFC as a predictor of time to, and age of, menopause. Supported by: NIH/NICHD/NIA R01 HD044876, Cedars (PI).
Monday, October 15, 2007 3:45 pm O-19 DOES BODY SIZE AFFECT MEASURES OF OVARIAN RESERVE IN LATE REPRODUCTIVE AGE WOMEN? I. H. Su, C. R. Gracia, M. D. Sammel, H. Lin, E. W. Freeman. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA; Biostatistics and Epidemiology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Research on Reproduction and Women’s Health, University of Pennsylvania School of Medicine, Philadelphia, PA; Departments of Obstetrics and Gynecology and Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA. OBJECTIVE: We have reported that anti-mullerian hormone (AMH) and inhibin B are decreased in obese women in late reproductive years. The study objectives were to explore the association between obesity and antral follicle count (AFC) and to further examine the association between obesity and hormonal markers of ovarian reserve. DESIGN: Cross-sectional. MATERIALS AND METHODS: Thirty-six healthy, late reproductive age women were recruited in a 1:1 ratio of normal weight (BMI<25) to obese women (BMI>30). All had regular menstrual cycles (q22–35), an intact uterus, both ovaries, and no hormone use. Subjects underwent a blood draw, anthropometric measurements and a transvaginal ultrasound in the first 4 days of a cycle. Blood was assayed for AMH, inhibin B, estradiol and follicle stimulating hormone (FSH). Body mass index (BMI), ovarian volume and AFC were recorded. A priori size calculations were conducted to detect a two-fold increase in the proportion of obese subjects with low AFC (<4) with 80% power. Bivariable analyses assessed the association between obesity, demographic variables, AFC, ovarian volume and hormone measures. Separate multivariable linear regression models were developed for AMH and inhibin B. RESULTS: Mean age was 45 (95% CI 41–49). Mean BMI (95% CI) was 22.4 (21.6–23.2) for normal weight and 37.6 (34.2–40.8) for obese subjects. Mean AFC (95% CI) was 7.6 (5–10.2) for lean and 6.3 (3.3–9.3) for obese subjects (P¼0.35). Proportions of normal weight (17%) vs. obese subjects (22%) with AFC less than 4 were similar (P¼0.8). Ovarian volumes did not differ by body size. AMH levels in obese women were 72% lower on average than in lean women, after adjusting for age, AFC, smoking and race
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