- Email: [email protected]
O-32
within 6 months (p⫽0.04). Patients with bilateral VV and mixed VV/EV had essentially equivalent times to patency, and both were significantly faster than patients with bilateral EV. By 6 months, 81% of patients with bilateral VV or mixed VV/EV achieved patency, compared to 31% of patients with bilateral EV (p⬍0.01). Clinically, patient age (ⱕ 40 years and ⬎40 years) was not associated with time to patency after bilateral VV.
CONCLUSION: Medications used for the treatment of depression may have a negative, reversible effect on male fertility. Serotonin-reuptake inhibitor antidepressants may affect sperm transport, resulting in impaired sperm motility and concentration for some patients. Further controlled studies of the effect of serotonin reuptake inhibitors on semen parameters are warranted to identify the clinically significant frequency of this effect. Supported by: None.
Monday, October 23, 2006 4:45 pm O-32 CONCLUSION: The intraoperative finding of motile sperm at either vas deferens predicts the shortest time to patency following vasectomy reversal, with virtually all patients achieving patency by 6 months. On the contrary, less than one-third of patients with bilateral EV showed patency within 6 months. This difference in the kinetics of sperm recovery is important to consider in cases of infertility due to vasectomy in the setting of advanced maternal age. Supported by: None.
Monday, October 23, 2006 4:30 pm O-31 ANTIDEPRESSANT-ASSOCIATED CHANGES IN SEMEN PARAMETERS. C. Tanrikut, P. N. Schlegel. New York Hospital/Cornell Medical Center, New York, NY. OBJECTIVE: To identify a relationship between antidepressant medication use and impaired semen parameters in a subset of male infertility patients. DESIGN: Case report. MATERIALS AND METHODS: We have identified two patients who have had severely impaired sperm concentration and motility closely associated with the use of antidepressant medications. We describe the temporal association between abnormal semen parameters and antidepressant therapy in these two patients (who had normal semen parameters off of any medication) and were identified during evaluation for male infertility. RESULTS: Physical examination and endocrinologic studies were unremarkable in each case. While on antidepressant medications, both patients produced semen samples with marked impairment of sperm concentration and/or motility. Each patient demonstrated a normalization of sperm concentration and motility after discontinuation of antidepressants. (Figures 1 & 2)
S14
Abstracts
PROPAGATION AND MATURATION OF MALE GONOCYTES IN VITRO. Q. V. Neri, N. Tanaka, T. Takeuchi, M. Toschi, Z. Rosenwaks, G. D. Palermo. Cornell Univ, New York, NY. OBJECTIVE: In mammals, millions of spermatozoa are produced daily, ultimately from spermatogonial stem cells (SSCs). The ability to propagate and immortalize SSCs in vitro would allow the creation of colonies which, on intra-testicular transfer, might be able to repopulate the germinal epithelium in azoospermic men with Sertoli-cell-only syndrome. DESIGN: Neonatal testicular cells were exposed to varying combinations of growth factors and gonadotropins for propagation and eventual differentiation. MATERIALS AND METHODS: Testes were obtained from 6-day-old B6 mice and the seminiferous tubules exposed to an enzymatic solution. Cell suspensions were sorted, counted, and evaluated for integrity and morphology. Testicular cells were plated in medium supplemented with GDNF, bFGF, FSH, and LIF. Cells were assessed for AP activity, Thy-1, and VASA to identify PGCs, SSCs, and spermatogenic cells. Histological sections of perfused embryos at E6.5 and E12.5 were studied, while FE-J1 and Scp1 were employed for assessment of post-meiotic stages. RESULTS: E6.5 sectioned embryos expressed VASA on the periphery of the epiblast, while in the E12.5 embryos both VASA and AP activity were localized in the gonadal ridge. Fourteen testes retrieved from seven-6-dpc mice had an average weight of 5.0mg⫾0.01. Sorting of 6 dissected testes (795,000 testicular cells) yielded 43,500 Thy-1⫹ cells with a ⬎80% enrichment rate (P⬍0.0001). After plating the germ cells on a feeder layer, one putative SSC colony proliferated up to day 9 of culture. The remaining eight testes provided about 1.1 million cells with 3% germ cells retrieved after enzymatic digestion. The unselected suspensions of testicular cells were plated under 1)GDNF⫹bFGF, 2)FSH⫹bFGF, 3)GDNF⫹bFGF⫹LIF. The following day, epithelial cells attached to the dish with scattered adherent germ cells. On D3, cell clumps of 25m diameter were uniformly distributed in the dish. There was a spontaneous and progressive migration of the somatic cells around each germ cell, creating dispersed cell clumps. In all media combination, cell aggregates gradually increased to reach a diameter of 100m by D10. In GDNF⫹bFGF and GDNF⫹bFGF⫹LIF they remained as tightly packed entities, whereas the clumps in FSH⫹bFGF started to spread out. When LIF was removed, cell aggregates behaved similarly to FSH⫹bFGF. The putative germ cells in these tridimensional structures were monitored for up to 75 days. Such cellular aggregates had a linear growth up to D56 and then plateaued. VASA expression and AP activity, at different days, were present mainly on the outside periphery of the aggregates and on some individual cells within, indicating that the germ cells were maintained for an extended time. The GDNF⫹bFGF supplemented with LIF was the most suitable to better support the germ cell population. Following administration of FSH and LH, it became possible to identify post-meiotic cells. CONCLUSION: Although enrichment and isolation of SSCs was suc-
Vol. 86, Suppl 2, September 2006
cessful, they proliferated on feeder cells only for a few days. On the other hand, the tridimensional support provided by testicular somatic cells along with essential growth factors, assured the proliferation and propagation of germ cells for an extended time. This work indicates that it may be possible to maintain human SSCs in culture that could be used to repopulate the testes of patients with sertoli-cell-only syndrome, or provide a direct source of haploidized male germ cells. Supported by: Institutional.
CONTRACEPTION SPECIAL INTEREST GROUP Monday, October 23, 2006 3:30 pm O-33 SHOULD LONG-TERM HORMONAL CONTRACEPTION BE RECONSIDERED? METABOLIC AND INFLAMMATORY OUTCOMES IN WOMEN USING ORAL CONTRACEPTIVES AND THE LEVONORGESTREL-RELEASING INTRAUTERINE DEVICE IN A GENERAL POPULATION. L. C. Morin-Papunen, H. Martikainen, M. I. McCarthy, S. Franks, M. Ja¨rvelin, A. Pouta. Univ Hospital, Oulu, Finland; Oxford Center for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom; Institute of Reproductive and Developmental Biology, Imperial Coll London, United Kingdom; Dept of Public Health Science and General Practice, Oulu, Finland; National Public Health Institute, Oulu, Finland. OBJECTIVE: Despite prolonged use during reproductive life, the impact of many commonly-used contraceptive agents on the risk of subsequent metabolic and cardiovascular disease remains controversial. We compared the metabolic and cardiovascular effects of two widely-used contraceptive regimes: the levonorgestrel-releasing intrauterine device (LNG-IUD) and oral contraceptives (OCs). DESIGN: We investigated the effects of the use of these two contraceptive regimes in a representative sample of 2814 women from a general population based Northern Finland Birth Cohort born in 1966. MATERIALS AND METHODS: A range of anthropometric, cardiovascular, metabolic and inflammatory phenotypes were measured at age 31 years. Women were classified as OC-users (N⫽687), LNG-IUD users (N⫽168) or using no hormonal contraception (reference group, N⫽1959). RESULTS: Compared to the reference group, OC-users had higher blood pressure (BP), systolic BP median 121 (interquartile range 114, 129) vs. 118 (111, 126) mmHg, and diastolic BP 76 (69, 82) vs. 74 (68, 82) mmHg, raised levels of inflammatory indices [C-reactive protein 1.90 (0.80-4.70) vs. 0.60 (0.30-1.40) mg/L], and impaired insulin sensitivity [lower homeostasis model assessment, HOMA%S 661 (547, 809) vs. 720 (578, 881)]. In contrast, LNG-IUD-users displayed no unfavorable changes in BP, lipid profile or insulin sensitivity, when compared to those on no hormonal contraception. CONCLUSION: OC-usage was associated with adverse changes in several metabolic, cardiovascular and inflammatory parameters, consistent with an increased future risk of cardiovascular and metabolic disease. No such changes were associated with LNG-IUD usage. These data suggest that non-oral hormonal contraception may offer long-term health benefits over oral methods. Supported by: Academy of Finland.
Monday, October 23, 2006 3:45 pm O-34 RETURN OF FERTILITY AFTER CESSATION OF A CONTINUOUS ORAL CONTRACEPTIVE. K. Barnhart, S. Mirkin, G. Grubb, G. Constantine. Penn Fertility Care, Univ of Pennsylvania, Philadelphia, PA; Wyeth Research, Collegeville, PA. OBJECTIVE: To evaluate the return to fertility among women planning to become pregnant after the use of a continuous oral contraceptive of levonorgestrel 90 g/ethinyl estradiol 20 g (LNG/EE). DESIGN: Prospective Observational Study. MATERIALS AND METHODS: After participation in a large phase 3
FERTILITY & STERILITY威
contraceptive trial of low dose continuous LNG/EE (n⫽ 2134), women who stated that they planned to become pregnant were followed for up to 12 months following their last dose of treatment. Eligible subjects were contacted twice (by phone, per protocol), at 3 and 12 months after discontinuation of continuous LNG/EE to determine whether they were pregnant. At each contact, subjects reported if and when they had conceived. If they were not pregnant, they were asked if they were still trying to conceive or if they had resumed contraception. A Kaplan-Meier analysis displaying the time until conception was performed. RESULTS: Of 30 subjects who stated that they planned to become pregnant and were not already pregnant, 4 initiated other contraception in the first month after discontinuation of the continuous oral contraceptive and 5 subjects were lost to follow up. For the remaining 21 subjects at risk of pregnancy, the average duration of treatment with LNG/EE continuously was 197 days (range, 28-364 days; SD ⫾ 120.6 days). The pregnancy rate was 57 % (12/21) at 3 months and 81% (17/21) at 12 months after discontinuation. After the 12-month post study follow-up, information was sought for the remaining 4 of 21 subjects who had not become pregnant. One subject conceived within 14 months of the last treatment for a total pregnancy rate of 86% (18/21). For the 3 remaining subjects who did not conceive, 1 subject had stopped trying to become pregnant by 12 months, and 2 women were lost to follow-up after 12 months. Eighteen pregnancies resulted in 17 live births and 1 in a spontaneous abortion. Data were obtained from 10 of the 17 newborns. All were uncomplicated term deliveries, with an Apgar score ⱖ 9 at five minutes. The average weight was 7 lb. 11 oz. with a range of 6 lb. 8 oz. to 9 lb. 0 oz. CONCLUSION: This is the first report of return to fertility after up to one year of use of a continuous oral contraceptive regimen. We reported a pregnancy rate of 81% at 12 months after the discontinuation of the LNG/EE continuous oral contraception. These findings indicate that a continuous-use regimen of levonorgestrel 90 g/ethinyl estradiol 20 g does not delay the return to fertility and is comparable to the reported return of fertility observed with cyclic combined oral contraceptives of about 80%-90% after 12 months post treatment. Supported by: Wyeth Research.
Monday, October 23, 2006 4:00 pm O-35 EVALUATION OF THE EFFECTS ON SERUM HORMONE LEVELS OF SUPPLEMENTATION WITH 10 MICROGRAMS ETHINYL ESTRADIOL DAILY DURING THE TYPICAL HORMONEFREE INTERVAL OF A COMBINED ORAL CONTRACEPTIVE. K. Z. Reape, C. E. Diliberti, C. H. Hendy. Duramed Research, Inc, Bala Cynwyd, PA; Barr Pharmaceuticals Inc., Woodcliff Lake, NJ; Novum Pharmaceutical Research Services, Pittsburgh, PA. OBJECTIVE: During the 7-day placebo or hormone-free interval (HFI) of a traditional 28-day oral contraceptive regimen, ethinyl estradiol (EE) is rapidly cleared from the circulation, allowing several hormone-free days in which recovery of the hypothalamic-pituitary-ovarian axis occurs and hormone levels approach those seen in normal ovulatory menstrual cycles. It has been suggested that this recovery increases the risk of follicular development and escape ovulation and may contribute to the occurrence of hormone-related symptoms. It has also been suggested that modification of the traditional HFI by supplementation with 10 micrograms (mcg) of EE may increase ovarian suppression. The aim of this study was to evaluate the effects of a 10 mcg/day dose of oral EE compared to placebo on ovarian activity as reflected by follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin-B levels, during the traditional 7-day HFI in female subjects already taking marketed formulations of combination oral contraceptive tablets containing 150 mcg levonorgestrel and 30 mcg EE. DESIGN: This was a prospective, two-arm, randomized, multicenter, open-label study. MATERIALS AND METHODS: Reproductive-aged females (18-35 years old; [median age-23]) currently taking a 28-day oral contraceptive containing 150 mcg levonorgestrel and 30 mcg EE for a minimum of two 28-day cycles were randomized to receive placebo (n⫽15) or 10 mcg EE (n⫽11) for 7 days following the completion of active combination tablets.
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CONCLUSION: Medications used for the treatment of depression may have a negative, reversible effect on male fertility. Serotonin-reuptake inhibitor antidepressants may affect sperm transport, resulting in impaired sperm motility and concentration for some patients. Further controlled studies of the effect of serotonin reuptake inhibitors on semen parameters are warranted to identify the clinically significant frequency of this effect. Supported by: None.
Monday, October 23, 2006 4:45 pm O-32 CONCLUSION: The intraoperative finding of motile sperm at either vas deferens predicts the shortest time to patency following vasectomy reversal, with virtually all patients achieving patency by 6 months. On the contrary, less than one-third of patients with bilateral EV showed patency within 6 months. This difference in the kinetics of sperm recovery is important to consider in cases of infertility due to vasectomy in the setting of advanced maternal age. Supported by: None.
Monday, October 23, 2006 4:30 pm O-31 ANTIDEPRESSANT-ASSOCIATED CHANGES IN SEMEN PARAMETERS. C. Tanrikut, P. N. Schlegel. New York Hospital/Cornell Medical Center, New York, NY. OBJECTIVE: To identify a relationship between antidepressant medication use and impaired semen parameters in a subset of male infertility patients. DESIGN: Case report. MATERIALS AND METHODS: We have identified two patients who have had severely impaired sperm concentration and motility closely associated with the use of antidepressant medications. We describe the temporal association between abnormal semen parameters and antidepressant therapy in these two patients (who had normal semen parameters off of any medication) and were identified during evaluation for male infertility. RESULTS: Physical examination and endocrinologic studies were unremarkable in each case. While on antidepressant medications, both patients produced semen samples with marked impairment of sperm concentration and/or motility. Each patient demonstrated a normalization of sperm concentration and motility after discontinuation of antidepressants. (Figures 1 & 2)
S14
Abstracts
PROPAGATION AND MATURATION OF MALE GONOCYTES IN VITRO. Q. V. Neri, N. Tanaka, T. Takeuchi, M. Toschi, Z. Rosenwaks, G. D. Palermo. Cornell Univ, New York, NY. OBJECTIVE: In mammals, millions of spermatozoa are produced daily, ultimately from spermatogonial stem cells (SSCs). The ability to propagate and immortalize SSCs in vitro would allow the creation of colonies which, on intra-testicular transfer, might be able to repopulate the germinal epithelium in azoospermic men with Sertoli-cell-only syndrome. DESIGN: Neonatal testicular cells were exposed to varying combinations of growth factors and gonadotropins for propagation and eventual differentiation. MATERIALS AND METHODS: Testes were obtained from 6-day-old B6 mice and the seminiferous tubules exposed to an enzymatic solution. Cell suspensions were sorted, counted, and evaluated for integrity and morphology. Testicular cells were plated in medium supplemented with GDNF, bFGF, FSH, and LIF. Cells were assessed for AP activity, Thy-1, and VASA to identify PGCs, SSCs, and spermatogenic cells. Histological sections of perfused embryos at E6.5 and E12.5 were studied, while FE-J1 and Scp1 were employed for assessment of post-meiotic stages. RESULTS: E6.5 sectioned embryos expressed VASA on the periphery of the epiblast, while in the E12.5 embryos both VASA and AP activity were localized in the gonadal ridge. Fourteen testes retrieved from seven-6-dpc mice had an average weight of 5.0mg⫾0.01. Sorting of 6 dissected testes (795,000 testicular cells) yielded 43,500 Thy-1⫹ cells with a ⬎80% enrichment rate (P⬍0.0001). After plating the germ cells on a feeder layer, one putative SSC colony proliferated up to day 9 of culture. The remaining eight testes provided about 1.1 million cells with 3% germ cells retrieved after enzymatic digestion. The unselected suspensions of testicular cells were plated under 1)GDNF⫹bFGF, 2)FSH⫹bFGF, 3)GDNF⫹bFGF⫹LIF. The following day, epithelial cells attached to the dish with scattered adherent germ cells. On D3, cell clumps of 25m diameter were uniformly distributed in the dish. There was a spontaneous and progressive migration of the somatic cells around each germ cell, creating dispersed cell clumps. In all media combination, cell aggregates gradually increased to reach a diameter of 100m by D10. In GDNF⫹bFGF and GDNF⫹bFGF⫹LIF they remained as tightly packed entities, whereas the clumps in FSH⫹bFGF started to spread out. When LIF was removed, cell aggregates behaved similarly to FSH⫹bFGF. The putative germ cells in these tridimensional structures were monitored for up to 75 days. Such cellular aggregates had a linear growth up to D56 and then plateaued. VASA expression and AP activity, at different days, were present mainly on the outside periphery of the aggregates and on some individual cells within, indicating that the germ cells were maintained for an extended time. The GDNF⫹bFGF supplemented with LIF was the most suitable to better support the germ cell population. Following administration of FSH and LH, it became possible to identify post-meiotic cells. CONCLUSION: Although enrichment and isolation of SSCs was suc-
Vol. 86, Suppl 2, September 2006
cessful, they proliferated on feeder cells only for a few days. On the other hand, the tridimensional support provided by testicular somatic cells along with essential growth factors, assured the proliferation and propagation of germ cells for an extended time. This work indicates that it may be possible to maintain human SSCs in culture that could be used to repopulate the testes of patients with sertoli-cell-only syndrome, or provide a direct source of haploidized male germ cells. Supported by: Institutional.
CONTRACEPTION SPECIAL INTEREST GROUP Monday, October 23, 2006 3:30 pm O-33 SHOULD LONG-TERM HORMONAL CONTRACEPTION BE RECONSIDERED? METABOLIC AND INFLAMMATORY OUTCOMES IN WOMEN USING ORAL CONTRACEPTIVES AND THE LEVONORGESTREL-RELEASING INTRAUTERINE DEVICE IN A GENERAL POPULATION. L. C. Morin-Papunen, H. Martikainen, M. I. McCarthy, S. Franks, M. Ja¨rvelin, A. Pouta. Univ Hospital, Oulu, Finland; Oxford Center for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom; Institute of Reproductive and Developmental Biology, Imperial Coll London, United Kingdom; Dept of Public Health Science and General Practice, Oulu, Finland; National Public Health Institute, Oulu, Finland. OBJECTIVE: Despite prolonged use during reproductive life, the impact of many commonly-used contraceptive agents on the risk of subsequent metabolic and cardiovascular disease remains controversial. We compared the metabolic and cardiovascular effects of two widely-used contraceptive regimes: the levonorgestrel-releasing intrauterine device (LNG-IUD) and oral contraceptives (OCs). DESIGN: We investigated the effects of the use of these two contraceptive regimes in a representative sample of 2814 women from a general population based Northern Finland Birth Cohort born in 1966. MATERIALS AND METHODS: A range of anthropometric, cardiovascular, metabolic and inflammatory phenotypes were measured at age 31 years. Women were classified as OC-users (N⫽687), LNG-IUD users (N⫽168) or using no hormonal contraception (reference group, N⫽1959). RESULTS: Compared to the reference group, OC-users had higher blood pressure (BP), systolic BP median 121 (interquartile range 114, 129) vs. 118 (111, 126) mmHg, and diastolic BP 76 (69, 82) vs. 74 (68, 82) mmHg, raised levels of inflammatory indices [C-reactive protein 1.90 (0.80-4.70) vs. 0.60 (0.30-1.40) mg/L], and impaired insulin sensitivity [lower homeostasis model assessment, HOMA%S 661 (547, 809) vs. 720 (578, 881)]. In contrast, LNG-IUD-users displayed no unfavorable changes in BP, lipid profile or insulin sensitivity, when compared to those on no hormonal contraception. CONCLUSION: OC-usage was associated with adverse changes in several metabolic, cardiovascular and inflammatory parameters, consistent with an increased future risk of cardiovascular and metabolic disease. No such changes were associated with LNG-IUD usage. These data suggest that non-oral hormonal contraception may offer long-term health benefits over oral methods. Supported by: Academy of Finland.
Monday, October 23, 2006 3:45 pm O-34 RETURN OF FERTILITY AFTER CESSATION OF A CONTINUOUS ORAL CONTRACEPTIVE. K. Barnhart, S. Mirkin, G. Grubb, G. Constantine. Penn Fertility Care, Univ of Pennsylvania, Philadelphia, PA; Wyeth Research, Collegeville, PA. OBJECTIVE: To evaluate the return to fertility among women planning to become pregnant after the use of a continuous oral contraceptive of levonorgestrel 90 g/ethinyl estradiol 20 g (LNG/EE). DESIGN: Prospective Observational Study. MATERIALS AND METHODS: After participation in a large phase 3
FERTILITY & STERILITY威
contraceptive trial of low dose continuous LNG/EE (n⫽ 2134), women who stated that they planned to become pregnant were followed for up to 12 months following their last dose of treatment. Eligible subjects were contacted twice (by phone, per protocol), at 3 and 12 months after discontinuation of continuous LNG/EE to determine whether they were pregnant. At each contact, subjects reported if and when they had conceived. If they were not pregnant, they were asked if they were still trying to conceive or if they had resumed contraception. A Kaplan-Meier analysis displaying the time until conception was performed. RESULTS: Of 30 subjects who stated that they planned to become pregnant and were not already pregnant, 4 initiated other contraception in the first month after discontinuation of the continuous oral contraceptive and 5 subjects were lost to follow up. For the remaining 21 subjects at risk of pregnancy, the average duration of treatment with LNG/EE continuously was 197 days (range, 28-364 days; SD ⫾ 120.6 days). The pregnancy rate was 57 % (12/21) at 3 months and 81% (17/21) at 12 months after discontinuation. After the 12-month post study follow-up, information was sought for the remaining 4 of 21 subjects who had not become pregnant. One subject conceived within 14 months of the last treatment for a total pregnancy rate of 86% (18/21). For the 3 remaining subjects who did not conceive, 1 subject had stopped trying to become pregnant by 12 months, and 2 women were lost to follow-up after 12 months. Eighteen pregnancies resulted in 17 live births and 1 in a spontaneous abortion. Data were obtained from 10 of the 17 newborns. All were uncomplicated term deliveries, with an Apgar score ⱖ 9 at five minutes. The average weight was 7 lb. 11 oz. with a range of 6 lb. 8 oz. to 9 lb. 0 oz. CONCLUSION: This is the first report of return to fertility after up to one year of use of a continuous oral contraceptive regimen. We reported a pregnancy rate of 81% at 12 months after the discontinuation of the LNG/EE continuous oral contraception. These findings indicate that a continuous-use regimen of levonorgestrel 90 g/ethinyl estradiol 20 g does not delay the return to fertility and is comparable to the reported return of fertility observed with cyclic combined oral contraceptives of about 80%-90% after 12 months post treatment. Supported by: Wyeth Research.
Monday, October 23, 2006 4:00 pm O-35 EVALUATION OF THE EFFECTS ON SERUM HORMONE LEVELS OF SUPPLEMENTATION WITH 10 MICROGRAMS ETHINYL ESTRADIOL DAILY DURING THE TYPICAL HORMONEFREE INTERVAL OF A COMBINED ORAL CONTRACEPTIVE. K. Z. Reape, C. E. Diliberti, C. H. Hendy. Duramed Research, Inc, Bala Cynwyd, PA; Barr Pharmaceuticals Inc., Woodcliff Lake, NJ; Novum Pharmaceutical Research Services, Pittsburgh, PA. OBJECTIVE: During the 7-day placebo or hormone-free interval (HFI) of a traditional 28-day oral contraceptive regimen, ethinyl estradiol (EE) is rapidly cleared from the circulation, allowing several hormone-free days in which recovery of the hypothalamic-pituitary-ovarian axis occurs and hormone levels approach those seen in normal ovulatory menstrual cycles. It has been suggested that this recovery increases the risk of follicular development and escape ovulation and may contribute to the occurrence of hormone-related symptoms. It has also been suggested that modification of the traditional HFI by supplementation with 10 micrograms (mcg) of EE may increase ovarian suppression. The aim of this study was to evaluate the effects of a 10 mcg/day dose of oral EE compared to placebo on ovarian activity as reflected by follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and inhibin-B levels, during the traditional 7-day HFI in female subjects already taking marketed formulations of combination oral contraceptive tablets containing 150 mcg levonorgestrel and 30 mcg EE. DESIGN: This was a prospective, two-arm, randomized, multicenter, open-label study. MATERIALS AND METHODS: Reproductive-aged females (18-35 years old; [median age-23]) currently taking a 28-day oral contraceptive containing 150 mcg levonorgestrel and 30 mcg EE for a minimum of two 28-day cycles were randomized to receive placebo (n⫽15) or 10 mcg EE (n⫽11) for 7 days following the completion of active combination tablets.
S15