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Lack of AMH Response to EFORT Suggests That AMH Production Is Gonadotropin-Independent in Adult Women
Spearman’s coefficient * P-waarde⬍0,05 ** P-waarde⬍0,01
responsible for the endocrine response and can be seen as a marker for the functional ovarian reserve. Supported by: This study was supported by a grant from the UMC Groningen and a grant from Organon NL. The Netherlands.
P-742 Lack of AMH Response to EFORT Suggests That AMH Production Is Gonadotropin-Independent in Adult Women. R. Fanchin, K. De Pawn, J. Taieb, M. Cavagna, E. Feyereisen, A. Dzik. Hospital A. Beclere, Clamart, France; Dept. Reproductive Medicine, Centro de Referencia da Saude da Mulher, Sao Paulo, Brazil. OBJECTIVE: In women, anti-Mu¨llerian hormone (AMH), a glycoprotein that belongs to the TGF superfamiliy, is produced by ovarian granulosa cells from ovarian follicles not only at the selectable stage but also at earlier stages, when follicles are barely FSH-sensitive. Whereas, in adult men, FSH administration has been shown to upregulate testicular AMH production in absence of testosterone (Young et al., 2005), direct data on the possible regulation of follicular AMH production by pituitary gonadotropins still is lacking. Hence, in an effort to challenge the hypothesis that ovarian AMH production in FSH-independent in adult women, we measured serum AMH dynamics after FSH administration in the early follicular phase, according to a modified exogenous FSH ovarian reserve test (EFORT) (Fanchin et al., 1994). DESIGN: Prospective study. MATERIALS AND METHODS: We studied 29 normo-ovulating, infertile patients. On cycle day 3 (BL), after blood samplings were obtained for serum AMH, E2, and inhibin B measurements, they received 300 IU of recombinant FSH, SC, (FSH group, n⫽14) or served as untreated controls (Control group, n⫽15). Twenty-four hours later (t24), patients underwent similar hormonal measurements as at BL. Changes in hormonal levels were expressed in % of increase from BL to t24 and differences in serum hormone levels between groups were assessed by using the Wilcoxon signed-rank test. RESULTS: FSH administration increased significantly serum E2 (182%, ranges: 38%-484%, P⬍ 0.0001) and inhibin B (95%, ranges: 0%-150%, P⬍ 0.0001), but not AMH (0.2%, ranges: -12.8%-19.8%) levels in the FSH group. Serum levels of all 3 hormones remained steady in the control group. CONCLUSION: These results indicate that FSH administration on cycle day 3 does not exert significant, short-term consequences in serum AMH levels, but induce a remarkable increase in serum E2 and inhibin B levels. The present data provide direct documentation that AMH production by functional granulosa cells probably is FSH-independent in adult women. Supported by: None.
P-743 Treatment of Overweight Women With Polycystic Ovaries (PCO) and Insulin Resistance (IR) With Rosiglitazone vs. Ethinyl Estradiol-Cyproterone Acetate Administered Alone and in Sequential Combinations. A. Lemay, S. Dodin, L. Turcot, F. De´cheˆne, J. Forest. CHUQ, Hoˆpital St-Franc¸ois d’Assise, Que´bec, PQ, Canada. OBJECTIVE: Few studies evaluated insulin sensitizers in association with oral contraceptives (OC) in PCO with IR. The purpose of this study was to assess the efficacy and possible interaction of a thiazolidinedione vs.
S424
Abstracts
an anti-androgenic oestrogen-progestin on the endocrine-metabolic problems of overweight PCO women. DESIGN: PCO candidates with BMI ⬎ 25 kg/m2 and high insulin (⬎ 90 pmol/L) not responding to a 4 months preparatory diet low in refined sugar were randomly assigned to rosiglitazone 4mg/day (group A) or to ethinyl estradiol 35ug/cyproterone acetate 2mg (EE/CPA: group B). After 6 months, each group received both medications for another 6 months for evaluation of additive/interactive effects. MATERIALS AND METHODS: Assessments at screening, at baseline after diet and every 3 months during treatment included biometrical changes, insulin levels, indices of IR and response to an oral glucose tolerance test (OGTT), lipid profile, androgens, clinical symptoms and safety laboratory tests. A group of 10 normal women served as reference values at baseline. RESULTS: Thirty-six percent of 50 admissible PCO candidates were not randomised since diet alone corrected their insulin level. Sixty-one percent of women completed the treatment periods (group A: n ⫽ 10 and group B: n ⫽ 7). As single treatment, rosiglitazone reduced insulin, IR indices (HOMA: homeostasis model assessment and QUICKI: quantitative sensitivity check index) and the insulin area under the curve (AUC) in response to OGTT but had little effect on lipids and androgens. EE/CPA alone did not modify insulin and its response to OGTT but improved low HDL-C, further increased TG, decreased testosterone, androstenedione and free androgen index (FAI). The above effects were similar during combined treatments indicating complementary favourable effects without apparent positive or negative interactions. No changes in diet, physical activity or anthropometric measures as assessed throughout the study could explain the above changes. When used as a single agent, rosiglitazone improved the frequency of menses. The similar decrease in hirsutism score in both groups at the end of the study appeared to be mainly related to the intake of EE/CPA. Both medications alone or combined did not cause appreciable side effects or changes in safety parameters. CONCLUSION: In obese PCO women with high insulin not corrected initially by diet corrections, the combination of rosiglitazone and EE/CPA was necessary to achieve complementary beneficial effects on endocrinemetabolic anomalies and clinical symptoms. The combined treatment was also without apparent antagonizing effects, noticeable side effects and changes in safety parameters. Further studies are required to evaluate the optimal treatment of an overweight PCO patient presenting with IR and requesting an OC. Supported by: Research supported by a grant from the Canadian Health Research Institutes.
P-744 Plasma Homocysteine, C-Reactive Protein and Insulin Resistance in Women With Polycystic Ovary Syndrome in Relation to Cardiovascular Risk Factors. A. A. Rouzi, M. S. Ardawi. King Abdulaziz University, Jeddah, Saudi Arabia. OBJECTIVE: To investigate the role of insulin resistance (IR) in contributing to cardiovascular risk factors among women with polycystic ovarian syndrome (PCOS) in relation to plasma levels of homocysteine and C-reactive protein. DESIGN: Prospective cohort study. MATERIALS AND METHODS: One hundred and thirty women at King Abdulaziz Universtiy Hospital, Jeddah, Saudi Arabia participated in this study. Sixty-five women with infertility and PCOS according to clinical, biochemical, and ultrasonographic criteria were compared to 65 agematched healthy controls. Each woman was requested to have a 75 g-oral glucose challenge test and fasting serum insulin, total cholesterol, triglycerides, LDL- and HDL-cholesterol, C-reactive protein and plasma homocysteine were also measured. Insulin resistance was determined by fasting serum insulin, glucose-to-insulin ratio (GIR) and homeostasis model assessment (HOMA). Cardiovascular risk factors score was calculated for each woman including: waist circumference, total cholesterol, HDL-cholesterol, systolic and diastolic blood pressure measurements and the presence of diabetes mellitus. RESULTS: The age of the women with PCOS (mean ⫾ SD) was 28.6 ⫾ 6.1 years and the age of the control group was 28.2 ⫾ 6.5 years. Women with PCOS who were hyperinsulinaemic (n ⫽ 26; insulin levels were 162 ⫾ 42 pmol/L) exhibited higher cardiovascular risk factors (composite score for cardiovascular risk factors ⫽ 2.59 ⫾ 1.20), higher homocysteine (14.5 ⫾
Vol. 84, Suppl 1, September 2005
responsible for the endocrine response and can be seen as a marker for the functional ovarian reserve. Supported by: This study was supported by a grant from the UMC Groningen and a grant from Organon NL. The Netherlands.
P-742 Lack of AMH Response to EFORT Suggests That AMH Production Is Gonadotropin-Independent in Adult Women. R. Fanchin, K. De Pawn, J. Taieb, M. Cavagna, E. Feyereisen, A. Dzik. Hospital A. Beclere, Clamart, France; Dept. Reproductive Medicine, Centro de Referencia da Saude da Mulher, Sao Paulo, Brazil. OBJECTIVE: In women, anti-Mu¨llerian hormone (AMH), a glycoprotein that belongs to the TGF superfamiliy, is produced by ovarian granulosa cells from ovarian follicles not only at the selectable stage but also at earlier stages, when follicles are barely FSH-sensitive. Whereas, in adult men, FSH administration has been shown to upregulate testicular AMH production in absence of testosterone (Young et al., 2005), direct data on the possible regulation of follicular AMH production by pituitary gonadotropins still is lacking. Hence, in an effort to challenge the hypothesis that ovarian AMH production in FSH-independent in adult women, we measured serum AMH dynamics after FSH administration in the early follicular phase, according to a modified exogenous FSH ovarian reserve test (EFORT) (Fanchin et al., 1994). DESIGN: Prospective study. MATERIALS AND METHODS: We studied 29 normo-ovulating, infertile patients. On cycle day 3 (BL), after blood samplings were obtained for serum AMH, E2, and inhibin B measurements, they received 300 IU of recombinant FSH, SC, (FSH group, n⫽14) or served as untreated controls (Control group, n⫽15). Twenty-four hours later (t24), patients underwent similar hormonal measurements as at BL. Changes in hormonal levels were expressed in % of increase from BL to t24 and differences in serum hormone levels between groups were assessed by using the Wilcoxon signed-rank test. RESULTS: FSH administration increased significantly serum E2 (182%, ranges: 38%-484%, P⬍ 0.0001) and inhibin B (95%, ranges: 0%-150%, P⬍ 0.0001), but not AMH (0.2%, ranges: -12.8%-19.8%) levels in the FSH group. Serum levels of all 3 hormones remained steady in the control group. CONCLUSION: These results indicate that FSH administration on cycle day 3 does not exert significant, short-term consequences in serum AMH levels, but induce a remarkable increase in serum E2 and inhibin B levels. The present data provide direct documentation that AMH production by functional granulosa cells probably is FSH-independent in adult women. Supported by: None.
P-743 Treatment of Overweight Women With Polycystic Ovaries (PCO) and Insulin Resistance (IR) With Rosiglitazone vs. Ethinyl Estradiol-Cyproterone Acetate Administered Alone and in Sequential Combinations. A. Lemay, S. Dodin, L. Turcot, F. De´cheˆne, J. Forest. CHUQ, Hoˆpital St-Franc¸ois d’Assise, Que´bec, PQ, Canada. OBJECTIVE: Few studies evaluated insulin sensitizers in association with oral contraceptives (OC) in PCO with IR. The purpose of this study was to assess the efficacy and possible interaction of a thiazolidinedione vs.
S424
Abstracts
an anti-androgenic oestrogen-progestin on the endocrine-metabolic problems of overweight PCO women. DESIGN: PCO candidates with BMI ⬎ 25 kg/m2 and high insulin (⬎ 90 pmol/L) not responding to a 4 months preparatory diet low in refined sugar were randomly assigned to rosiglitazone 4mg/day (group A) or to ethinyl estradiol 35ug/cyproterone acetate 2mg (EE/CPA: group B). After 6 months, each group received both medications for another 6 months for evaluation of additive/interactive effects. MATERIALS AND METHODS: Assessments at screening, at baseline after diet and every 3 months during treatment included biometrical changes, insulin levels, indices of IR and response to an oral glucose tolerance test (OGTT), lipid profile, androgens, clinical symptoms and safety laboratory tests. A group of 10 normal women served as reference values at baseline. RESULTS: Thirty-six percent of 50 admissible PCO candidates were not randomised since diet alone corrected their insulin level. Sixty-one percent of women completed the treatment periods (group A: n ⫽ 10 and group B: n ⫽ 7). As single treatment, rosiglitazone reduced insulin, IR indices (HOMA: homeostasis model assessment and QUICKI: quantitative sensitivity check index) and the insulin area under the curve (AUC) in response to OGTT but had little effect on lipids and androgens. EE/CPA alone did not modify insulin and its response to OGTT but improved low HDL-C, further increased TG, decreased testosterone, androstenedione and free androgen index (FAI). The above effects were similar during combined treatments indicating complementary favourable effects without apparent positive or negative interactions. No changes in diet, physical activity or anthropometric measures as assessed throughout the study could explain the above changes. When used as a single agent, rosiglitazone improved the frequency of menses. The similar decrease in hirsutism score in both groups at the end of the study appeared to be mainly related to the intake of EE/CPA. Both medications alone or combined did not cause appreciable side effects or changes in safety parameters. CONCLUSION: In obese PCO women with high insulin not corrected initially by diet corrections, the combination of rosiglitazone and EE/CPA was necessary to achieve complementary beneficial effects on endocrinemetabolic anomalies and clinical symptoms. The combined treatment was also without apparent antagonizing effects, noticeable side effects and changes in safety parameters. Further studies are required to evaluate the optimal treatment of an overweight PCO patient presenting with IR and requesting an OC. Supported by: Research supported by a grant from the Canadian Health Research Institutes.
P-744 Plasma Homocysteine, C-Reactive Protein and Insulin Resistance in Women With Polycystic Ovary Syndrome in Relation to Cardiovascular Risk Factors. A. A. Rouzi, M. S. Ardawi. King Abdulaziz University, Jeddah, Saudi Arabia. OBJECTIVE: To investigate the role of insulin resistance (IR) in contributing to cardiovascular risk factors among women with polycystic ovarian syndrome (PCOS) in relation to plasma levels of homocysteine and C-reactive protein. DESIGN: Prospective cohort study. MATERIALS AND METHODS: One hundred and thirty women at King Abdulaziz Universtiy Hospital, Jeddah, Saudi Arabia participated in this study. Sixty-five women with infertility and PCOS according to clinical, biochemical, and ultrasonographic criteria were compared to 65 agematched healthy controls. Each woman was requested to have a 75 g-oral glucose challenge test and fasting serum insulin, total cholesterol, triglycerides, LDL- and HDL-cholesterol, C-reactive protein and plasma homocysteine were also measured. Insulin resistance was determined by fasting serum insulin, glucose-to-insulin ratio (GIR) and homeostasis model assessment (HOMA). Cardiovascular risk factors score was calculated for each woman including: waist circumference, total cholesterol, HDL-cholesterol, systolic and diastolic blood pressure measurements and the presence of diabetes mellitus. RESULTS: The age of the women with PCOS (mean ⫾ SD) was 28.6 ⫾ 6.1 years and the age of the control group was 28.2 ⫾ 6.5 years. Women with PCOS who were hyperinsulinaemic (n ⫽ 26; insulin levels were 162 ⫾ 42 pmol/L) exhibited higher cardiovascular risk factors (composite score for cardiovascular risk factors ⫽ 2.59 ⫾ 1.20), higher homocysteine (14.5 ⫾
Vol. 84, Suppl 1, September 2005