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Defining the menopausal transition: A new definition to detect early hormonal changes in women
echogenic gray layers), and 5 patients exhibited a type C EP (homogenous, hyperechogenic endometrium). Endometrial thickness was measured in millimeters. Data were analyzed by Fisher’s exact test, unpaired t test and/or logistic regression with Statview software. Clinical pregnancy was the primary outcome variable. Two-tailed p⬍0.05 was considered significant. Sample size was determined by study interval, and not power analysis. Results: Overall, clinical pregnancy was established in 64% of the 447 patients after transfer of embryos at the blastocyst or morula stage of development. Two hundred fifty-four of the 376 (68%) pattern A patients became pregnant versus 31 of the 66 (47%) of pattern B patients (P ⫽ 0.0024). There was no statistically significant relationship between pattern A and B patients with regard to the variables of endometrial thickness (P ⫽ 0.37), age (P ⫽ 0.58), ART method (P ⫽ 0.23) or number of embryos transferred (P ⫽ 0.17). Excluding the 41 women who had only morula transferred, the difference in pregnancy between patterns A and B remained significant (P ⫽ 0.013) for women who had a blastocyst transfer. Of the 5 women with pattern C endometrium, 3 became pregnant. If patients with B and C patterns were combined and compared to group A, as other investigators have suggested, there was still a significant difference between groups (P ⫽ 0.0028). Conclusion: The presence of a B pattern endometrium on the day of hCG administration was associated with a significant reduction in clinical pregnancy in women undergoing blastocyst transfer. These results suggest that the endometrium may represent an obstacle to the establishment of pregnancy at ART for some patients. However, in patients with a B pattern, we would still proceed with embryo transfer rather than cryopreservation, since 47% of these patients achieved pregnancy. Based on these findings, further characterization of the endometrium defined as B pattern by ultrasound may identify barriers to implantation. Supported by: Division of Intramural Research, NICHD.
MENOPAUSE SPECIAL INTEREST GROUP Monday, October 13, 2003 2:00 P.M. O-39 Defining the menopausal transition: A new definition to detect early hormonal changes in women. Clarisa R. Gracia, Mary D. Sammel, Ellen W. Freeman, Li Liu, Elizabeth Langan, Deborah Nelson. Univ of Pennsylvania, Philadelphia, PA. Objective: The menopausal transition is not an abrupt event, but rather a process, occurring over time. Since the age of onset and duration of this period varies greatly among women, age alone is not a good indicator of where a particular woman falls in this continuum. At least three different staging systems based on menstrual changes are being used in cohort studies to define changes during the menopause. The objective of this study is to determine which staging system best distinguishes menopausal stages in women, using hormone values as the gold standard measure of menopausal status. We also propose a new definition to help differentiate the earliest hormonal changes during this transition. Design: Prospective cohort study. Methods: Women aged 35– 47 years old identified through random digit dialing were prospectively followed for 5 years with assessments at approximately 8-month intervals. At each assessment period, hormones were measured on two occasions one month apart during the first 6 days of the cycle, if cycling, and standardized questionnaires were administered. Women were classified as premenopaual, early transition, late transition, and post-menopausal by three different staging systems defined by bleeding pattern. The SWAN study definition, STRAW consensus definition, and the Penn Ovarian Aging definitions were used. Using a 4-by-4 table approach, it was clear that women in the early stages of transition were classified differently by the various staging systems. A new staging system with 5 groups rather than 4 was created to help distinguish women in the earliest stages: premenopausal ⫽ no change in cycle length; early transition A ⫽ 7 day or more change in 1 cycle (from personal baseline cycle length); early transition B ⫽ 7 day or more change in 2 cycles; late transition ⫽ 3-11 months of no bleeding; post-menopausal ⫽ at least 12 months of no bleeding. For each staging system (SWAN, STRAW, Penn Ovarian Aging, New definition), a linear regression model was created comparing mean hormone values at assessment 7 among stages. We adjusted for race, body
FERTILITY & STERILITY威
mass index, cycle day, and smoking in this model. Log transformed mean follicle stimulating hormone (FSH), estradiol, and inhibin B were assessed in separate models. Results: We found that each of the 3 preexisting staging systems equally distinguished later menopausal stages in this cohort. No consistent statistically significant differences in mean hormone measures were detected among the stages. We observed trends in hormone levels with changing menopausal status consistent with findings from other studies. When we examined results from our new staging system, we were able to detect statistically significant differences in mean inhibin B levels at the earliest menopausal stages (28.8pg/mL premenopausal vs. 20.9pg/mL early transition A; p ⫽ .01). We were not able to detect a statistically significant difference in FSH or estradiol between these two groups. Conclusions: Overall, current menopausal staging systems appear to be equivalent in their ability to distinguish subjects who have progressed to late and post menopausal states. We have created a new staging system that appears to be able to discriminate inhibin B levels in women with very early changes in cycle length. Subtle differences in bleeding pattern are important in defining a woman’s menopausal status, as they correspond with significant differences in hormone measures.
Monday, October 13, 2003 2:15 P.M. O-40 The Factor V Leiden polymorphism is associated with early menopause in Caucasian women. Eva-Katrin Riener, Clemens B. Tempfer, Lukas A. Hefler, Christian Schneeberger, Johannes C. Huber. Univ of Freiburg, Freiburg, Germany; Univ of Vienna, Vienna, Austria. Objective: Polymorphisms in genes encoding Factor V and ProthrombinFactor II, known to be key components of the coagulation cascade, are also thought to influence reproductive functions in humans. Materials and Methods: We investigated the influence of the Factor V Leiden G1691A and the Prothrombin-Factor II G20210A gene polymorphisms on timing of menarche and menopause in 154 Caucasian women. Results: Presence of the Factor V Leiden G1691A polymorphism significantly influenced timing of menopause overall, i.e., natural and surgical menopause combined (42.6 ⫹ 6.8 yr vs. 48.5 ⫹ 5.2 yr, p ⫽ 0.005), and timing of natural menopause (42.2 ⫹ 8 yr vs. 49.6 ⫹ 4.1 yr, p ⫽ 0.001), but not the timing of menarche and the risk for undergoing hysterectomy. The Prothrombin-Factor G20210A polymorphism was not associated with any of the investigated parameters. Smokers experienced menopause significantly earlier than non-smokers. Body Mass Index, age at first full-time pregnancy, and number of children did not influence timing of menopause. Conclusion: We conclude that presence of a polymorphic allele of Factor V Leiden and smoking habits are significant predictors of early menopause. Women should be counseled accordingly.
Monday, October 13, 2003 2:30 P.M. O-41 Identification of osteoporosis risk in postmenopausal women by the combined use of ultrasounds and clinical factors. Umberto Omodei, Caterina Benussi, Michela Feller, Laura Decca, Marco Gambacciani. Univ of Brescia, Brescia, Italy; Univ of Pisa, Pisa, Italy. Objective: Dual Energy X-ray Absorptiometry (DEXA) is considered the gold standard for osteoporosis diagnosis and identification of postmenopausal women at high risk for osteoporotic fractures. However DEXA supposes the use of expensive and not easily available instruments. The aim of this study was to verify the possibility of identifying osteoporotic patients by the association of clinical-anamnestic algorithms with ultrasonographical bone evaluation, using portable, noninvasive, and less expensive instrument. Design: Two hundred twenty-four postmenopausal women (57.9⫾6.2 years old) were recruited at the Menopause Clinic in Brescia and Pisa. All subjects were evaluated by ultrasonography at the phalanxes (DBM Sonic BP) and by DEXA at the femur and lumbar spine (Hologic QDR 4500 W
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MENOPAUSE SPECIAL INTEREST GROUP Monday, October 13, 2003 2:00 P.M. O-39 Defining the menopausal transition: A new definition to detect early hormonal changes in women. Clarisa R. Gracia, Mary D. Sammel, Ellen W. Freeman, Li Liu, Elizabeth Langan, Deborah Nelson. Univ of Pennsylvania, Philadelphia, PA. Objective: The menopausal transition is not an abrupt event, but rather a process, occurring over time. Since the age of onset and duration of this period varies greatly among women, age alone is not a good indicator of where a particular woman falls in this continuum. At least three different staging systems based on menstrual changes are being used in cohort studies to define changes during the menopause. The objective of this study is to determine which staging system best distinguishes menopausal stages in women, using hormone values as the gold standard measure of menopausal status. We also propose a new definition to help differentiate the earliest hormonal changes during this transition. Design: Prospective cohort study. Methods: Women aged 35– 47 years old identified through random digit dialing were prospectively followed for 5 years with assessments at approximately 8-month intervals. At each assessment period, hormones were measured on two occasions one month apart during the first 6 days of the cycle, if cycling, and standardized questionnaires were administered. Women were classified as premenopaual, early transition, late transition, and post-menopausal by three different staging systems defined by bleeding pattern. The SWAN study definition, STRAW consensus definition, and the Penn Ovarian Aging definitions were used. Using a 4-by-4 table approach, it was clear that women in the early stages of transition were classified differently by the various staging systems. A new staging system with 5 groups rather than 4 was created to help distinguish women in the earliest stages: premenopausal ⫽ no change in cycle length; early transition A ⫽ 7 day or more change in 1 cycle (from personal baseline cycle length); early transition B ⫽ 7 day or more change in 2 cycles; late transition ⫽ 3-11 months of no bleeding; post-menopausal ⫽ at least 12 months of no bleeding. For each staging system (SWAN, STRAW, Penn Ovarian Aging, New definition), a linear regression model was created comparing mean hormone values at assessment 7 among stages. We adjusted for race, body
FERTILITY & STERILITY威
mass index, cycle day, and smoking in this model. Log transformed mean follicle stimulating hormone (FSH), estradiol, and inhibin B were assessed in separate models. Results: We found that each of the 3 preexisting staging systems equally distinguished later menopausal stages in this cohort. No consistent statistically significant differences in mean hormone measures were detected among the stages. We observed trends in hormone levels with changing menopausal status consistent with findings from other studies. When we examined results from our new staging system, we were able to detect statistically significant differences in mean inhibin B levels at the earliest menopausal stages (28.8pg/mL premenopausal vs. 20.9pg/mL early transition A; p ⫽ .01). We were not able to detect a statistically significant difference in FSH or estradiol between these two groups. Conclusions: Overall, current menopausal staging systems appear to be equivalent in their ability to distinguish subjects who have progressed to late and post menopausal states. We have created a new staging system that appears to be able to discriminate inhibin B levels in women with very early changes in cycle length. Subtle differences in bleeding pattern are important in defining a woman’s menopausal status, as they correspond with significant differences in hormone measures.
Monday, October 13, 2003 2:15 P.M. O-40 The Factor V Leiden polymorphism is associated with early menopause in Caucasian women. Eva-Katrin Riener, Clemens B. Tempfer, Lukas A. Hefler, Christian Schneeberger, Johannes C. Huber. Univ of Freiburg, Freiburg, Germany; Univ of Vienna, Vienna, Austria. Objective: Polymorphisms in genes encoding Factor V and ProthrombinFactor II, known to be key components of the coagulation cascade, are also thought to influence reproductive functions in humans. Materials and Methods: We investigated the influence of the Factor V Leiden G1691A and the Prothrombin-Factor II G20210A gene polymorphisms on timing of menarche and menopause in 154 Caucasian women. Results: Presence of the Factor V Leiden G1691A polymorphism significantly influenced timing of menopause overall, i.e., natural and surgical menopause combined (42.6 ⫹ 6.8 yr vs. 48.5 ⫹ 5.2 yr, p ⫽ 0.005), and timing of natural menopause (42.2 ⫹ 8 yr vs. 49.6 ⫹ 4.1 yr, p ⫽ 0.001), but not the timing of menarche and the risk for undergoing hysterectomy. The Prothrombin-Factor G20210A polymorphism was not associated with any of the investigated parameters. Smokers experienced menopause significantly earlier than non-smokers. Body Mass Index, age at first full-time pregnancy, and number of children did not influence timing of menopause. Conclusion: We conclude that presence of a polymorphic allele of Factor V Leiden and smoking habits are significant predictors of early menopause. Women should be counseled accordingly.
Monday, October 13, 2003 2:30 P.M. O-41 Identification of osteoporosis risk in postmenopausal women by the combined use of ultrasounds and clinical factors. Umberto Omodei, Caterina Benussi, Michela Feller, Laura Decca, Marco Gambacciani. Univ of Brescia, Brescia, Italy; Univ of Pisa, Pisa, Italy. Objective: Dual Energy X-ray Absorptiometry (DEXA) is considered the gold standard for osteoporosis diagnosis and identification of postmenopausal women at high risk for osteoporotic fractures. However DEXA supposes the use of expensive and not easily available instruments. The aim of this study was to verify the possibility of identifying osteoporotic patients by the association of clinical-anamnestic algorithms with ultrasonographical bone evaluation, using portable, noninvasive, and less expensive instrument. Design: Two hundred twenty-four postmenopausal women (57.9⫾6.2 years old) were recruited at the Menopause Clinic in Brescia and Pisa. All subjects were evaluated by ultrasonography at the phalanxes (DBM Sonic BP) and by DEXA at the femur and lumbar spine (Hologic QDR 4500 W
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