- Email: [email protected]
Androgen administration in normal reproductive-age women promotes proatherogenic inflammation as characterized in polycystic ovary syndrome (PCOS)
steroidogenic enzymes (CYP11A1, CYP17A1) was evaluated by qrt-PCR. Androstenedione and androsterone levels in culture media were determined using liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test. RESULTS: SIM decreased androstenedione levels in culture media by 92% (P<0.001) and androsterone production by 60% (P<0.001), whereas the addition of RES to SIM-treated cultures decreased androstenedione levels by 79-88% (P<0.001) and androsterone production by 82-91% (P<0.001), respectively. SIM inhibited both CYP11A1 and CYP17A1 gene expression, respectively, by 24% (P<0.001) and 87% (P<0.001). However, RES in combination with SIM decreased both CYP11A1 and CYP17A1 gene expression, respectively, by 55-72% (P<0.001) and 95-99% (P<0.001). CONCLUSION: SIM inhibits androgen production in theca-interstitial cells, and this SIM-induced decrease in steroidogenesis is enhanced by the addition of RES. The present findings may lead to the development of novel treatments of PCOS involving a combination of SIM and RES. Supported by: Eunice Kennedy Shriver NICHD Grant RO1 HD050656
O-136 Tuesday, October 18, 2011 05:00 PM METFORMIN INHIBITS CELL PROLIFERATION AND CELL CYCLE REGULATORY PROTEINS OF OVARIAN THECA-INTERSTITIAL CELLS. M. A. Will, M. Palaniappan, H. Peegel, P. Kayampilly, K. M. J. Menon. Obstetrics and Gynecology, University of Michigan Hospitals, Ann Arbor, MI. OBJECTIVE: Metformin, an oral biguanide used to treat diabetes, insulin resistance, and polycystic ovary syndrome (PCOS) has been found to have anti-neoplastic properties related to activation of AMP-activated protein kinase (AMPK), a well-known intracellular regulator of energy metabolism and cell proliferation. Since PCOS is characterized by hyperplasia of ovarian theca-interstitial (TI) cells, our objective was to evaluate if metformin exerts a direct inhibitory effect on ovarian TI cell proliferation. DESIGN: In vitro experimental study. MATERIALS AND METHODS: Purified TI cells were isolated from immature rats and cultured in the absence (control) or presence of metformin and/or insulin (1 mcg/mL). Intracellular effects of metformin were evaluated with Western blot for phosphorylated (activated) and total AMPK. Cell proliferation was assessed by Western blot analysis of proteins involved in cell cycle progression, cyclin D3 and cyclin-dependent kinase 4 (CDK4). DNA synthesis was determined by bromodeoxyuridine (BrdU) incorporation assay. Data were analyzed using one-way ANOVA followed by Tukey’s test. RESULTS: Metformin induced a concentration dependent activation of AMPK in TI cells and inhibition of ovarian TI cell proliferation. DNA synthesis in cells treated with metformin (3mM and 10mM) and insulin for 24 hours was reduced by 25% and 37%, respectively, compared to cells treated with insulin alone (P<0.001). Metformin (3mM) also significantly decreased insulin-induced expression of cyclin D3 and CDK4 by 20% and 35%, respectively, after 18 hours of treatment, compared with insulin alone (P<0.05). CONCLUSION: Metformin activates AMPK and inhibits proliferation of ovarian TI cells. Present findings further validate potential benefits of metformin in the treatment of conditions associated with hyperinsulinemia and excessive growth of ovarian theca-interstitial cells (such as PCOS) and provide a foundation for further studies evaluating pathways involved in theca cell proliferation. Supported by: NIH grant HD 38424.
O-137 Tuesday, October 18, 2011 05:15 PM THE IMPACT OF SUPERVISED WEIGHT LOSS AND WEIGHT REGAIN ON THE ANDROGENIC SEX HORMONE PROFILE: SEX HORMONE BINDING GLOBULIN IS THE MOST SENSITIVE MARKER OF WEIGHT FLUCTUATIONS. M. Aubuchon, A. J. Polotsky, Y. Liu, T. R. Thomas. Obstetrics, Gynecology, and Women’s Health, University of Missouri School of Medicine, Columbia, MO; Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO; Nutrition & Exercise Physiology-Health and Exercise Science, University of Missouri School of Medicine, Columbia, MO. OBJECTIVE: In women, altered androgens are associated with increased metabolic and cardiovascular risk. The objective was to determine the effects of weight loss followed by weight regain on androgen levels. DESIGN: Secondary analysis of stored blood samples.
FERTILITY & STERILITYÒ
MATERIALS AND METHODS: 32 obese menstruating women (mean age of 39.9 6.7 years, mean baseline body mass index of 32.8 4.1 kilogram (kg)/meter2) with metabolic syndrome underwent supervised 10% weight loss (8.6 kg on average) over 4-6 months followed by supervised regain of 50% of the lost weight (4.7 kg on average) over 4-6 months with or without exercise. Log-transformation was applied for non-normal distributions. Changes from baseline, post weight loss, and post weight regain for log-transformed (for skewed distributions) sex hormone binding globulin (LogSHBG), total testosterone (LogTes), free androgen index (LogFAI), and high molecular weight adiponectin (LogHMWAdp) were evaluated. Comparisons of exercise and nonexercise were conducted with Student t test. Repeated measures analysis of variance (ANOVA) was used as appropriate with post-hoc Tukey HSD test. RESULTS: Insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI) improved with weight loss and were maintained despite weight regain and increased % body fat. LogSHBG significantly increased from baseline to weight loss, then significantly decreased with weight regain. LogTes, LogFAI, and LogHMWAdp showed no changes. There were no significant differences by exercise between the groups. CONCLUSION: Although weight loss exerts favorable metabolic changes that are maintained despite weight regain, the effect of weight loss on SHBG is reversed with weight regain. The prominent sensitivity of SHBG to body mass fluctuations suggests that it could be an important marker of the interactions between the metabolic and reproductive systems in obese women. Supported by: University of Missouri Research Council grant (DeptID C2648057 Project CR000307)
O-138 Tuesday, October 18, 2011 05:30 PM ANDROGEN ADMINISTRATION IN NORMAL REPRODUCTIVEAGE WOMEN PROMOTES PROATHEROGENIC INFLAMMATION AS CHARACTERIZED IN POLYCYSTIC OVARY SYNDROME (PCOS). F. Gonzalez, K. S. Nair, E. Basal, D. M. Bearson, J. M. Schimke, H. E. Blair. Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN; (a) Internal Medicine, (b) Obstetrics and Gynecology, and (c) Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN. OBJECTIVE: In PCOS, increased protein expression of MMP-2, a promoter of atherosclerotic plaque rupture, directly correlates with circulating androgens in the fasting state. IL-6 and CRP are also proatherogenic. We examined the effect of oral androgen administration in normal reproductive-age women on the expression of MMP-2 protein and IL-6 RNA in mononuclear cells (MNC), and on plasma IL-6 and CRP while fasting, and following glucose ingestion. DESIGN: Prospective, controlled study. MATERIALS AND METHODS: Sixteen lean ovulatory women (ages 18-40) without androgen excess ingested a 75 gm glucose beverage before and after orally ingesting 130 mg of DHEA (n ¼ 8) or placebo (n ¼ 8) for 5 days, in a randomized double-blind fashion. Expression of MMP-2 protein and IL-6 RNA was quantified in isolated MNC by Western blotting and RT-PCR, respectively; and plasma IL-6 and CRP levels were measured by ELISA, from blood samples drawn fasting and 2 hours after glucose ingestion. RESULTS: Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens, or any of the proatherogenic inflammatory markers while fasting or after glucose ingestion. Compared to placebo, DHEA treatment raised levels of testosterone (123 9 vs. 45 4 ng/dl, P<0.0001) and androstenedione (2.2 0.1 vs. 1.5 0.1 ng/ml, P<0.002). In the fasting state, DHEA treatment increased the percent change in MMP-2 protein (19.2 10.2 vs. -3.6 3.0, P<0.05), IL6 RNA (49.2 24.2 vs. -14.4 15.6, P<0.05), plasma IL-6 (42.4 19.0 vs. -3.8 9.8 P<0.05) and plasma CRP (14.3 6.8 vs. -4.8 5.8, P<0.05) compared to placebo. There were no differences in any of these parameters after DHEA vs. placebo in response to glucose ingestion. CONCLUSION: Fasting MMP-2 protein, IL-6 RNA, and circulating IL-6 and CRP increase in normal reproductive-age women after raising circulating androgens to levels observed in PCOS. Thus, hyperandrogenemia activates
S41
a proatherogenic inflammatory response, but below the threshold to sensitize MNC to glucose in this population. Supported by: NIH grant HD048535 to F.G.
Supported by: NIH/DHHS NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495
O-140 Tuesday, October 18, 2011 06:00 PM O-139 Tuesday, October 18, 2011 05:45 PM HISTORY OF OLIGOMENORRHEA AUGMENTS THE ASSOCIATION OF HYPERANDROGENEMIA WITH METABOLIC SYNDROME: EVIDENCE FOR A PCOS PHENOTYPE IN THE STUDY OF WOMEN’S HEALTH ACROSS THE NATION (SWAN). A. J. Polotsky, A. Allshouse, S. L. Crawford, S. D. Harlow, N. Khalil, R. S. Legro. Obstetrics and Gynecology, University of Colorado, Aurora, CO; Epidemiology, University of Michigan, Ann Arbor, MI; Community Health, Boonshoft School of Medicine, Dayton, OH; Obstetrics and Gynecology, Pennsylvania State University, Hershey, PA; Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA. OBJECTIVE: To evaluate the metabolic impact of serum testosterone (T) & menstrual irregularity (Oligo) in midlife women DESIGN: Cross-sectional. MATERIALS AND METHODS: SWAN is a multi-ethnic cohort of over 3000 US women as they traverse menopause. Those with a lifetime history of more than one 3-month stretch of non-gestational or non-lactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum T was set as hyperandrogenemia (HA). Metabolic syndrome (MetS) was defined by NCEP ATP III criteria. A logistic regression model of MetS was estimated, with adjustment for age, ethnicity, BMI, smoking, & site. RESULTS: Among the analytic sample of 2297 women (mean age 45.8), prevalence of each component of MetS was highest for subjects with both HA and Oligo.
Metabolic Parameters by Menstrual Regularity and Serum Androgens Androgen status
HA
Menstrual regularity
Oligo
Waist circumference2, cm Triglycerides > 150 mg/dl, %(n) HDL Cholesterol <50 mg/dl, %(n) High blood pressure, %(n) Impaired fasting glucose or diabetes, %(n) MetS, Unadjusted OR(95%CI) MetS, Adjusted OR(95%CI)
P1
Normal
Normal
Oligo
Normal
92.5 (89.4-95.7)
86.9 (84.7-89.16)
86.4 (85.4-87.4)
83.3 < .01 (82.6-84.0)
30.4 (38)
18.5 (43)
20.1 (168)
16.5 (272) < .01
50.4 (67)
36.8 (89)
37.8 (330)
33.6 (584) < .01
47.6 (64)
38.8 (94)
36.5 (320)
29.9 (522) < .01
23.0 (31)
11.2 (27)
11.8 (103)
8.6 (150) < .01
3.2 (2.2-4.7)
1.5 (1.3-1.9)
1.4 (1.0-2.0)
1
2.1 (1.3-3.2)
1.3 (1.0-1.7)
1.2 (0.7-1.7)
1
Multivariate analysis revealed that HA conferred a significant risk for MetS for all subjects, while Oligo was only associated with the outcome when coincident with HA. There was no significant interaction between the HA and Oligo in any models tested. 1 P value from chi-square 2 geometric mean, 95%CI CONCLUSION: HA confers detrimental metabolic risk for prevalent MetS independent of other factors (including BMI) in SWAN. Oligo augments this impact. Longitudinal follow-up would reveal the risk of incident MetS.
S42
Abstracts
COMPARATIVE STUDY OF THE THERAPEUTIC EFFECTS OF ORAL PILLS CONTAINING DESOGESTREL, CYPROTERONE ACETATE AND DROSPIRENONE, IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME (PCOS). S. M. Bhattacharya, A. Jha. Obstetrics & Gynecology, S.C. Das Memorial Medical & Research Center, Kolkata, West Bengal, India; Obstetrics & Gynecology, KPC Medical College, Kolkata, West Bengal, India; Division of Epidemiology and Communicable diseases(ECD), Indian Council of Medical Research (ICMR) Head Quarters, New Delhi, India. OBJECTIVE: To compare the therapeutic effects of three oral pills containing desogestrel, cyproterone acetate and drospirenone, in women with polycystic ovary syndrome (PCOS), after six and twelve months of therapy. DESIGN: Single-blind, randomized controlled trial. MATERIALS AND METHODS: 171 women with PCOS (Androgen excess society criteria, 2006), with pre-set inclusion-exclusion criteria, were randomized into 3 groups, receiving desogestrel (n ¼ 58), cyproterone acetate (n ¼ 56), and drospirenone (n ¼ 57) pills cyclically in traditional (21+7) regimen. The primary outcome was comparison of the change in the free androgen index (FAI) between the three groups, at 6 and 12 months of treatment. Body mass index, abdominal circumference, Ferriman- Galwey (F: G) score, presence of acne and acanthosis nigricans were assessed. Serum testosterone, sex hormone binding globulin (SHBG), fasting sugar and fasting insulin levels were measured. RESULTS: Intent-to-treat analysis established that after 6 months of treatment, studied parameters did not demonstrate any significant difference between the 3 groups, irrespective of the progestogen component. In contrast, after 12 months of therapy, cyproterone pill significantly decreased F: G score compared to both desogestrel (post hoc P¼0.003) and drospirenone (post hoc P¼0.02) pills. SHBG level was significantly increased by both cyproterone (post hoc P¼0.002) and drospirenone (post hoc P¼0.035) pills, over desogestrel pill. The FAI was significantly decreased by the cyproterone pill over desogestrel (post hoc P¼0.001). CONCLUSION: Therapeutic effects of the three pills, with different progestogens, are comparable after the first 6 months of treatment. After 12 months, the cyproterone acetate pill shows much stronger anti-androgen activities followed by drospirenone and then desogestrel pills. Effects on metabolic parameters are almost identical. Selection of the pill should depend on the degree of hyperandrogenism in PCOS. CTRI registration no. -CTRI/2010/091/000332
CRYOPRESERVATION AND FROZEN EMBRYO TRANSFER – CLINICAL: ART O-141 Tuesday, October 18, 2011 04:15 PM SAFETY OF PREGNANCY AFTER LETROZOLE-FSH STIMULATION IN BREAST CANCER PATIENTS: A PROSPECTIVE COMPARISON OF FROZEN EMBRYO TRANSFER TO SELF VS. GESTATIONAL CARRIERS. K. Oktay, E. Arslan, M. Karsy, F. Moy. Department of Obstetrics & Gynecology, Institute for Fertility Preservation, Laboratory of Molecular Reproduction, New York Medical College, Valhalla, NY; Department of Pathology, New York Medical College, Valhalla, NY; Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY. OBJECTIVE: Ovarian stimulation with aromatase inhibitor letrozole along with FSH has been suggested as a safe and efficient for women with breast cancer (BCa) undergoing oocyte or embryo cryopreservation for fertility preservation. However, cancer recurrence rates among those who successfully conceived have not been reported with this protocol to this date and some still consider gestational carriers (GC) to avoid risk. Our objective was to compare the outcomes and safety of pregnancy after frozen embryo transfer (FET) to self (ST) vs. GC. DESIGN: Prospective. MATERIALS AND METHODS: 143 women with BCa %Stage-3 underwent ovarian stimulation with letrozole (5mg/day) starting on cycle day 2 (CD2) and gonadotropins 150-450 IU on CD4 to cryopreserve embryos before chemotherapy. Oocyte maturation was triggered either with hCG (n ¼
Vol. 96., No. 3, Supplement, September 2011
O-136 Tuesday, October 18, 2011 05:00 PM METFORMIN INHIBITS CELL PROLIFERATION AND CELL CYCLE REGULATORY PROTEINS OF OVARIAN THECA-INTERSTITIAL CELLS. M. A. Will, M. Palaniappan, H. Peegel, P. Kayampilly, K. M. J. Menon. Obstetrics and Gynecology, University of Michigan Hospitals, Ann Arbor, MI. OBJECTIVE: Metformin, an oral biguanide used to treat diabetes, insulin resistance, and polycystic ovary syndrome (PCOS) has been found to have anti-neoplastic properties related to activation of AMP-activated protein kinase (AMPK), a well-known intracellular regulator of energy metabolism and cell proliferation. Since PCOS is characterized by hyperplasia of ovarian theca-interstitial (TI) cells, our objective was to evaluate if metformin exerts a direct inhibitory effect on ovarian TI cell proliferation. DESIGN: In vitro experimental study. MATERIALS AND METHODS: Purified TI cells were isolated from immature rats and cultured in the absence (control) or presence of metformin and/or insulin (1 mcg/mL). Intracellular effects of metformin were evaluated with Western blot for phosphorylated (activated) and total AMPK. Cell proliferation was assessed by Western blot analysis of proteins involved in cell cycle progression, cyclin D3 and cyclin-dependent kinase 4 (CDK4). DNA synthesis was determined by bromodeoxyuridine (BrdU) incorporation assay. Data were analyzed using one-way ANOVA followed by Tukey’s test. RESULTS: Metformin induced a concentration dependent activation of AMPK in TI cells and inhibition of ovarian TI cell proliferation. DNA synthesis in cells treated with metformin (3mM and 10mM) and insulin for 24 hours was reduced by 25% and 37%, respectively, compared to cells treated with insulin alone (P<0.001). Metformin (3mM) also significantly decreased insulin-induced expression of cyclin D3 and CDK4 by 20% and 35%, respectively, after 18 hours of treatment, compared with insulin alone (P<0.05). CONCLUSION: Metformin activates AMPK and inhibits proliferation of ovarian TI cells. Present findings further validate potential benefits of metformin in the treatment of conditions associated with hyperinsulinemia and excessive growth of ovarian theca-interstitial cells (such as PCOS) and provide a foundation for further studies evaluating pathways involved in theca cell proliferation. Supported by: NIH grant HD 38424.
O-137 Tuesday, October 18, 2011 05:15 PM THE IMPACT OF SUPERVISED WEIGHT LOSS AND WEIGHT REGAIN ON THE ANDROGENIC SEX HORMONE PROFILE: SEX HORMONE BINDING GLOBULIN IS THE MOST SENSITIVE MARKER OF WEIGHT FLUCTUATIONS. M. Aubuchon, A. J. Polotsky, Y. Liu, T. R. Thomas. Obstetrics, Gynecology, and Women’s Health, University of Missouri School of Medicine, Columbia, MO; Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO; Nutrition & Exercise Physiology-Health and Exercise Science, University of Missouri School of Medicine, Columbia, MO. OBJECTIVE: In women, altered androgens are associated with increased metabolic and cardiovascular risk. The objective was to determine the effects of weight loss followed by weight regain on androgen levels. DESIGN: Secondary analysis of stored blood samples.
FERTILITY & STERILITYÒ
MATERIALS AND METHODS: 32 obese menstruating women (mean age of 39.9 6.7 years, mean baseline body mass index of 32.8 4.1 kilogram (kg)/meter2) with metabolic syndrome underwent supervised 10% weight loss (8.6 kg on average) over 4-6 months followed by supervised regain of 50% of the lost weight (4.7 kg on average) over 4-6 months with or without exercise. Log-transformation was applied for non-normal distributions. Changes from baseline, post weight loss, and post weight regain for log-transformed (for skewed distributions) sex hormone binding globulin (LogSHBG), total testosterone (LogTes), free androgen index (LogFAI), and high molecular weight adiponectin (LogHMWAdp) were evaluated. Comparisons of exercise and nonexercise were conducted with Student t test. Repeated measures analysis of variance (ANOVA) was used as appropriate with post-hoc Tukey HSD test. RESULTS: Insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI) improved with weight loss and were maintained despite weight regain and increased % body fat. LogSHBG significantly increased from baseline to weight loss, then significantly decreased with weight regain. LogTes, LogFAI, and LogHMWAdp showed no changes. There were no significant differences by exercise between the groups. CONCLUSION: Although weight loss exerts favorable metabolic changes that are maintained despite weight regain, the effect of weight loss on SHBG is reversed with weight regain. The prominent sensitivity of SHBG to body mass fluctuations suggests that it could be an important marker of the interactions between the metabolic and reproductive systems in obese women. Supported by: University of Missouri Research Council grant (DeptID C2648057 Project CR000307)
O-138 Tuesday, October 18, 2011 05:30 PM ANDROGEN ADMINISTRATION IN NORMAL REPRODUCTIVEAGE WOMEN PROMOTES PROATHEROGENIC INFLAMMATION AS CHARACTERIZED IN POLYCYSTIC OVARY SYNDROME (PCOS). F. Gonzalez, K. S. Nair, E. Basal, D. M. Bearson, J. M. Schimke, H. E. Blair. Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN; (a) Internal Medicine, (b) Obstetrics and Gynecology, and (c) Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN. OBJECTIVE: In PCOS, increased protein expression of MMP-2, a promoter of atherosclerotic plaque rupture, directly correlates with circulating androgens in the fasting state. IL-6 and CRP are also proatherogenic. We examined the effect of oral androgen administration in normal reproductive-age women on the expression of MMP-2 protein and IL-6 RNA in mononuclear cells (MNC), and on plasma IL-6 and CRP while fasting, and following glucose ingestion. DESIGN: Prospective, controlled study. MATERIALS AND METHODS: Sixteen lean ovulatory women (ages 18-40) without androgen excess ingested a 75 gm glucose beverage before and after orally ingesting 130 mg of DHEA (n ¼ 8) or placebo (n ¼ 8) for 5 days, in a randomized double-blind fashion. Expression of MMP-2 protein and IL-6 RNA was quantified in isolated MNC by Western blotting and RT-PCR, respectively; and plasma IL-6 and CRP levels were measured by ELISA, from blood samples drawn fasting and 2 hours after glucose ingestion. RESULTS: Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens, or any of the proatherogenic inflammatory markers while fasting or after glucose ingestion. Compared to placebo, DHEA treatment raised levels of testosterone (123 9 vs. 45 4 ng/dl, P<0.0001) and androstenedione (2.2 0.1 vs. 1.5 0.1 ng/ml, P<0.002). In the fasting state, DHEA treatment increased the percent change in MMP-2 protein (19.2 10.2 vs. -3.6 3.0, P<0.05), IL6 RNA (49.2 24.2 vs. -14.4 15.6, P<0.05), plasma IL-6 (42.4 19.0 vs. -3.8 9.8 P<0.05) and plasma CRP (14.3 6.8 vs. -4.8 5.8, P<0.05) compared to placebo. There were no differences in any of these parameters after DHEA vs. placebo in response to glucose ingestion. CONCLUSION: Fasting MMP-2 protein, IL-6 RNA, and circulating IL-6 and CRP increase in normal reproductive-age women after raising circulating androgens to levels observed in PCOS. Thus, hyperandrogenemia activates
S41
a proatherogenic inflammatory response, but below the threshold to sensitize MNC to glucose in this population. Supported by: NIH grant HD048535 to F.G.
Supported by: NIH/DHHS NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495
O-140 Tuesday, October 18, 2011 06:00 PM O-139 Tuesday, October 18, 2011 05:45 PM HISTORY OF OLIGOMENORRHEA AUGMENTS THE ASSOCIATION OF HYPERANDROGENEMIA WITH METABOLIC SYNDROME: EVIDENCE FOR A PCOS PHENOTYPE IN THE STUDY OF WOMEN’S HEALTH ACROSS THE NATION (SWAN). A. J. Polotsky, A. Allshouse, S. L. Crawford, S. D. Harlow, N. Khalil, R. S. Legro. Obstetrics and Gynecology, University of Colorado, Aurora, CO; Epidemiology, University of Michigan, Ann Arbor, MI; Community Health, Boonshoft School of Medicine, Dayton, OH; Obstetrics and Gynecology, Pennsylvania State University, Hershey, PA; Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA. OBJECTIVE: To evaluate the metabolic impact of serum testosterone (T) & menstrual irregularity (Oligo) in midlife women DESIGN: Cross-sectional. MATERIALS AND METHODS: SWAN is a multi-ethnic cohort of over 3000 US women as they traverse menopause. Those with a lifetime history of more than one 3-month stretch of non-gestational or non-lactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum T was set as hyperandrogenemia (HA). Metabolic syndrome (MetS) was defined by NCEP ATP III criteria. A logistic regression model of MetS was estimated, with adjustment for age, ethnicity, BMI, smoking, & site. RESULTS: Among the analytic sample of 2297 women (mean age 45.8), prevalence of each component of MetS was highest for subjects with both HA and Oligo.
Metabolic Parameters by Menstrual Regularity and Serum Androgens Androgen status
HA
Menstrual regularity
Oligo
Waist circumference2, cm Triglycerides > 150 mg/dl, %(n) HDL Cholesterol <50 mg/dl, %(n) High blood pressure, %(n) Impaired fasting glucose or diabetes, %(n) MetS, Unadjusted OR(95%CI) MetS, Adjusted OR(95%CI)
P1
Normal
Normal
Oligo
Normal
92.5 (89.4-95.7)
86.9 (84.7-89.16)
86.4 (85.4-87.4)
83.3 < .01 (82.6-84.0)
30.4 (38)
18.5 (43)
20.1 (168)
16.5 (272) < .01
50.4 (67)
36.8 (89)
37.8 (330)
33.6 (584) < .01
47.6 (64)
38.8 (94)
36.5 (320)
29.9 (522) < .01
23.0 (31)
11.2 (27)
11.8 (103)
8.6 (150) < .01
3.2 (2.2-4.7)
1.5 (1.3-1.9)
1.4 (1.0-2.0)
1
2.1 (1.3-3.2)
1.3 (1.0-1.7)
1.2 (0.7-1.7)
1
Multivariate analysis revealed that HA conferred a significant risk for MetS for all subjects, while Oligo was only associated with the outcome when coincident with HA. There was no significant interaction between the HA and Oligo in any models tested. 1 P value from chi-square 2 geometric mean, 95%CI CONCLUSION: HA confers detrimental metabolic risk for prevalent MetS independent of other factors (including BMI) in SWAN. Oligo augments this impact. Longitudinal follow-up would reveal the risk of incident MetS.
S42
Abstracts
COMPARATIVE STUDY OF THE THERAPEUTIC EFFECTS OF ORAL PILLS CONTAINING DESOGESTREL, CYPROTERONE ACETATE AND DROSPIRENONE, IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME (PCOS). S. M. Bhattacharya, A. Jha. Obstetrics & Gynecology, S.C. Das Memorial Medical & Research Center, Kolkata, West Bengal, India; Obstetrics & Gynecology, KPC Medical College, Kolkata, West Bengal, India; Division of Epidemiology and Communicable diseases(ECD), Indian Council of Medical Research (ICMR) Head Quarters, New Delhi, India. OBJECTIVE: To compare the therapeutic effects of three oral pills containing desogestrel, cyproterone acetate and drospirenone, in women with polycystic ovary syndrome (PCOS), after six and twelve months of therapy. DESIGN: Single-blind, randomized controlled trial. MATERIALS AND METHODS: 171 women with PCOS (Androgen excess society criteria, 2006), with pre-set inclusion-exclusion criteria, were randomized into 3 groups, receiving desogestrel (n ¼ 58), cyproterone acetate (n ¼ 56), and drospirenone (n ¼ 57) pills cyclically in traditional (21+7) regimen. The primary outcome was comparison of the change in the free androgen index (FAI) between the three groups, at 6 and 12 months of treatment. Body mass index, abdominal circumference, Ferriman- Galwey (F: G) score, presence of acne and acanthosis nigricans were assessed. Serum testosterone, sex hormone binding globulin (SHBG), fasting sugar and fasting insulin levels were measured. RESULTS: Intent-to-treat analysis established that after 6 months of treatment, studied parameters did not demonstrate any significant difference between the 3 groups, irrespective of the progestogen component. In contrast, after 12 months of therapy, cyproterone pill significantly decreased F: G score compared to both desogestrel (post hoc P¼0.003) and drospirenone (post hoc P¼0.02) pills. SHBG level was significantly increased by both cyproterone (post hoc P¼0.002) and drospirenone (post hoc P¼0.035) pills, over desogestrel pill. The FAI was significantly decreased by the cyproterone pill over desogestrel (post hoc P¼0.001). CONCLUSION: Therapeutic effects of the three pills, with different progestogens, are comparable after the first 6 months of treatment. After 12 months, the cyproterone acetate pill shows much stronger anti-androgen activities followed by drospirenone and then desogestrel pills. Effects on metabolic parameters are almost identical. Selection of the pill should depend on the degree of hyperandrogenism in PCOS. CTRI registration no. -CTRI/2010/091/000332
CRYOPRESERVATION AND FROZEN EMBRYO TRANSFER – CLINICAL: ART O-141 Tuesday, October 18, 2011 04:15 PM SAFETY OF PREGNANCY AFTER LETROZOLE-FSH STIMULATION IN BREAST CANCER PATIENTS: A PROSPECTIVE COMPARISON OF FROZEN EMBRYO TRANSFER TO SELF VS. GESTATIONAL CARRIERS. K. Oktay, E. Arslan, M. Karsy, F. Moy. Department of Obstetrics & Gynecology, Institute for Fertility Preservation, Laboratory of Molecular Reproduction, New York Medical College, Valhalla, NY; Department of Pathology, New York Medical College, Valhalla, NY; Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY. OBJECTIVE: Ovarian stimulation with aromatase inhibitor letrozole along with FSH has been suggested as a safe and efficient for women with breast cancer (BCa) undergoing oocyte or embryo cryopreservation for fertility preservation. However, cancer recurrence rates among those who successfully conceived have not been reported with this protocol to this date and some still consider gestational carriers (GC) to avoid risk. Our objective was to compare the outcomes and safety of pregnancy after frozen embryo transfer (FET) to self (ST) vs. GC. DESIGN: Prospective. MATERIALS AND METHODS: 143 women with BCa %Stage-3 underwent ovarian stimulation with letrozole (5mg/day) starting on cycle day 2 (CD2) and gonadotropins 150-450 IU on CD4 to cryopreserve embryos before chemotherapy. Oocyte maturation was triggered either with hCG (n ¼
Vol. 96., No. 3, Supplement, September 2011