- Email: [email protected]
Efficacy and safety of venlafaxine for premenstrual dysphoric disorder
Methods: The Council on Resident Education in Obstetrics and Gynecology training guidelines were used to determine our cognitive and technical objectives. Two half-hour lectures were followed by an OSCE with four skills stations. Program participants were evaluated cognitively with a 25-question examination, and each participant was objectively rated on level of technical confidence in performing 20 common laparoscopic tasks before the OSCE and after the skills stations were complete. Results: There were 29 program participants, including 18 ob-gyn residents, 7 medical students, and 4 staff members. The overall technical confidence survey score improved from 61.7 to 79.6 (P ⫽ 0.005), and the examination scores improved from 51.5% to 95.1% (P ⫽ 0.0003). Technical confidence scores and cognitive scores improved at all year levels. Conclusion: Our Lapar-OSCE improved both laparoscopic technical confidence and laparoscopic surgical knowledge in our department. We believe that a standardized program for evaluating and improving operative laparoscopic technique will improve operator confidence and skill and may decrease operative time, complications, and anesthesia exposure in our patient population.
Acne Treatment with a Low-Dose Oral Contraceptive Melissa Gilliam, MD, MPH University of Illinois at Chicago, IL
G. Elam, MD, J. M. Maloney, M. R. Flack, MD, C. L. Sevilla, PhD, C. J. M. McLaughlin-Miley, PharmD, and R. Derman, MD Objective: To test whether a lower-dose oral contraceptive (Estrostep) that reduces circulating androgens is effective in acne treatment. Methods: Five hundred ninety-three women, aged 13– 49 years, were enrolled in two 6-cycle, randomized, placebocontrolled, parallel-group, multicenter studies; 297 received Estrostep (1 mg norethindrone acetate and 20, 30, and 35 g ethinyl estradiol) and 296 placebo. Demographics and discontinuation rates were similar across the two studies and between treatment groups. Efficacy was determined by changes in acne lesion counts, investigator’s overall rating of facial acne, subject assessment of acne severity, and acne-specific quality-of-life questionnaires. Results: Estrostep-treated subjects had greater decreases from baseline in all acne lesion counts relative to placebo (P ⬍0.0001) and a higher proportion of investigator ratings of absent or minimal facial acne (P ⫽ 0.0004). Eighty-four percent of Estrostep-treated subjects assessed their acne severity as improved at study exit, and there were significant increases in acne-specific quality of life (P ⬍0.0001). Conclusion: Estrostep is efficacious in the treatment of moderate acne vulgaris, providing an alternative to higher-dose oral contraceptives.
VOL. 97, NO 4 (SUPPLEMENT), APRIL 2001
Effect of a New Monophasic Oral Contraceptive on Perimenstrual Symptoms* Candace Brown, PharmD University of Tennessee, Memphis, TN
Frank Ling, MD, and Jim Wan, PhD Introduction: Drospirenone (DRSP) is a novel progestin with antimineralocorticoid and antiandrogenic activities. Methods: In this open-label, multicenter study, 322 healthy women aged 18 to 35 years used a monophasic oral contraceptive consisting of 30 g ethinyl estradiol (EE) and 3 mg DRSP for six cycles. Subjects completed a 23-item Women’s Health Assessment Questionnaire (WHAQ) at baseline and at the end of the sixth cycle. The WHAQ scored symptoms on a five-point scale during the premenstrual and menstrual phases and during the rest of the cycle (postmenstrual phase). Results: At baseline, mean scores for negative affect, water retention, and impaired concentration were higher during the premenstrual and menstrual phases than during the postmenstrual phase. At the end of cycle 6, premenstrual and menstrual symptom scores of negative affect and water retention were reduced significantly relative to baseline (P ⬍0.001), with similar improvements seen among women who were new users of hormonal contraceptives (P ⬍0.01) and those who switched from their previous contraceptives (P ⬍0.001). Impaired concentration scores were not significantly reduced from baseline. Conclusions: These results suggest that an oral contraceptive containing DRSP/EE may reduce perimenstrual symptoms, notably those related to negative affect and water retention. A controlled, prospective trial in women with more severe perimenstrual symptoms is needed to confirm these findings.
Efficacy and Safety of Venlafaxine for Premenstrual Dysphoric Disorder Ellen W. Freeman, PhD University of Pennsylvania, Philadelphia, PA
Steven J. Sondheimer, MD, Karl Rickels, MD, Mary Kay McPherson, MS, and Nadia R. Kunz, PharmD Objective: Some serotonergic antidepressants have been effective in treating premenstrual dysphoric disorder (PMDD). This study evaluated the efficacy of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, for treating PMDD. * This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.
Tuesday Papers 9S
Method: One hunded fifty-seven women were randomly assigned to double-blind treatment with venlafaxine or placebo for four menstrual cycles. Dosing ranged from 50 –200 mg/day with dose adjustments for lack of efficacy or AEs early in each cycle. Primary outcome was the total Daily Symptom Report (DSR) scores. Results: At the end of the first cycle, venlafaxine was significantly better than placebo (P ⬍ 0.001). Improvement slightly increased in the second cycle and was maintained for the remaining 2 months (P ⬍0.001 versus placebo). Mean premenstrual-week dose ranged from 50 –130 mg/day. Seven subjects (9%) in the venlafaxine group and 5 (6%) in the placebo group discontinued treatment because of adverse effects (AEs). Overall mild and transient, AEs included nausea (45% versus 13%), insomnia (35% versus 16%), and dizziness (32% versus 5%). Conclusions: Venlafaxine was effective and well tolerated in the treatment of PMDD. Improvement was seen early (first cycle) and at a relatively low dose.
and years since menopause was 6.2. All routes and concentrations of PC resulted in significant decrease in EPS from pretreatment and posttreatment EMB (P ⬍0.05). Both topical and vaginal placebo groups showed no difference in their EPS pretreatment and posttreatment EMB. Aversion to the application of PC was 35 % in the vaginal group versus 0% in the topical group. Conclusion: Topical and vaginal application of progesterone cream appears to have an antiproliferative effect on the endometrium. Patients preferred the topical application of progesterone cream.
Safety Profile: Transdermal Testosterone Treatment of Women After Oophorectomy* James A. Simon, MD
THIRD PRIZE PAPER Topical Progesterone Cream Has Antiproliferative Effect on Estrogen-Stimulated Endometrium James N. Anasti, MD St. Luke’s Hospital, Bethlehem, PA
H.B. Leonetti, MD, and K.J. Wilson, PhD Objective: Transdermal progesterone cream (PC) has become a popular alternative to hormone replacement therapy despite the lack of control trials. We designed a study to determine the effect of topical PC on the estrogen-stimulated endometrium of postmenopausal women. Method: Healthy postmenopausal women underwent an initial EMB after 14 days of oral estrogens only (0.625 mg conjugated equine estrogen [CEE]). Subjects then were randomized to 4 weeks of daily CEE with twice-daily application of vaginal or topical PC in various concentrations (placebo, 1.5%, 4%). A final EMB was performed after the 4 weeks of CEE and PC treatment. The EMBs were scored as to the degree of proliferation (EPS). The pretreatment and posttreatment EPS then were compared by ANOVA of ranks. Results: Fifty-eight women finished the study. The average age was 55.2 years, body mass index (BMI) was 26.7 kg/m2,
10S Tuesday Papers
Women’s Health Research Center, Laurel, MD
Norman A. Mazer, MD, PhD, and Kathryn Wekselman, RN, PhD Purpose: To evaluate the safety of two doses of testosterone (T) administered by investigational transdermal matrix patch to women with impaired sexual function after surgical menopause. Methods: Seventy-five women, aged 31–56 years, 1 to 10 years after TAH-BSO, received oral conjugated equine estrogens and, in random order, placebo, 150 g T, and 300 g T per day transdermally for 12 weeks each. Results: Serum-free and bioavailable T increased to normal values with both T treatments. Dihydrotestosterone and total T increased to above normal with 300 g T treatment, a finding related to higher than normal SHBG levels in women on oral estrogen. The hormones DHEA-S, estradiol, estrone, LH, FSH, and other safety parameters, hirsutism and acne scores, total cholesterol, HDL, LDL, triglycerides, hematocrit, platelets, WBC, bilirubin, AST, GGT, albumin, fasting glucose, insulin, heart rate, blood pressure, and hot flush frequency were not significantly affected by T treatment. Facial depilation rates (times/month) were similar for baseline (0.5), placebo (0.8) and 150 g T (0.7) and rose slightly for 300 g T (1.4). Adverse events during T and placebo treatments were comparable. One woman withdrew because of a skin reaction to the placebo patch; three others withdrew because of adverse events possibly or probably related to treatment.
* This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.
Obstetrics & Gynecology
Acne Treatment with a Low-Dose Oral Contraceptive Melissa Gilliam, MD, MPH University of Illinois at Chicago, IL
G. Elam, MD, J. M. Maloney, M. R. Flack, MD, C. L. Sevilla, PhD, C. J. M. McLaughlin-Miley, PharmD, and R. Derman, MD Objective: To test whether a lower-dose oral contraceptive (Estrostep) that reduces circulating androgens is effective in acne treatment. Methods: Five hundred ninety-three women, aged 13– 49 years, were enrolled in two 6-cycle, randomized, placebocontrolled, parallel-group, multicenter studies; 297 received Estrostep (1 mg norethindrone acetate and 20, 30, and 35 g ethinyl estradiol) and 296 placebo. Demographics and discontinuation rates were similar across the two studies and between treatment groups. Efficacy was determined by changes in acne lesion counts, investigator’s overall rating of facial acne, subject assessment of acne severity, and acne-specific quality-of-life questionnaires. Results: Estrostep-treated subjects had greater decreases from baseline in all acne lesion counts relative to placebo (P ⬍0.0001) and a higher proportion of investigator ratings of absent or minimal facial acne (P ⫽ 0.0004). Eighty-four percent of Estrostep-treated subjects assessed their acne severity as improved at study exit, and there were significant increases in acne-specific quality of life (P ⬍0.0001). Conclusion: Estrostep is efficacious in the treatment of moderate acne vulgaris, providing an alternative to higher-dose oral contraceptives.
VOL. 97, NO 4 (SUPPLEMENT), APRIL 2001
Effect of a New Monophasic Oral Contraceptive on Perimenstrual Symptoms* Candace Brown, PharmD University of Tennessee, Memphis, TN
Frank Ling, MD, and Jim Wan, PhD Introduction: Drospirenone (DRSP) is a novel progestin with antimineralocorticoid and antiandrogenic activities. Methods: In this open-label, multicenter study, 322 healthy women aged 18 to 35 years used a monophasic oral contraceptive consisting of 30 g ethinyl estradiol (EE) and 3 mg DRSP for six cycles. Subjects completed a 23-item Women’s Health Assessment Questionnaire (WHAQ) at baseline and at the end of the sixth cycle. The WHAQ scored symptoms on a five-point scale during the premenstrual and menstrual phases and during the rest of the cycle (postmenstrual phase). Results: At baseline, mean scores for negative affect, water retention, and impaired concentration were higher during the premenstrual and menstrual phases than during the postmenstrual phase. At the end of cycle 6, premenstrual and menstrual symptom scores of negative affect and water retention were reduced significantly relative to baseline (P ⬍0.001), with similar improvements seen among women who were new users of hormonal contraceptives (P ⬍0.01) and those who switched from their previous contraceptives (P ⬍0.001). Impaired concentration scores were not significantly reduced from baseline. Conclusions: These results suggest that an oral contraceptive containing DRSP/EE may reduce perimenstrual symptoms, notably those related to negative affect and water retention. A controlled, prospective trial in women with more severe perimenstrual symptoms is needed to confirm these findings.
Efficacy and Safety of Venlafaxine for Premenstrual Dysphoric Disorder Ellen W. Freeman, PhD University of Pennsylvania, Philadelphia, PA
Steven J. Sondheimer, MD, Karl Rickels, MD, Mary Kay McPherson, MS, and Nadia R. Kunz, PharmD Objective: Some serotonergic antidepressants have been effective in treating premenstrual dysphoric disorder (PMDD). This study evaluated the efficacy of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, for treating PMDD. * This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.
Tuesday Papers 9S
Method: One hunded fifty-seven women were randomly assigned to double-blind treatment with venlafaxine or placebo for four menstrual cycles. Dosing ranged from 50 –200 mg/day with dose adjustments for lack of efficacy or AEs early in each cycle. Primary outcome was the total Daily Symptom Report (DSR) scores. Results: At the end of the first cycle, venlafaxine was significantly better than placebo (P ⬍ 0.001). Improvement slightly increased in the second cycle and was maintained for the remaining 2 months (P ⬍0.001 versus placebo). Mean premenstrual-week dose ranged from 50 –130 mg/day. Seven subjects (9%) in the venlafaxine group and 5 (6%) in the placebo group discontinued treatment because of adverse effects (AEs). Overall mild and transient, AEs included nausea (45% versus 13%), insomnia (35% versus 16%), and dizziness (32% versus 5%). Conclusions: Venlafaxine was effective and well tolerated in the treatment of PMDD. Improvement was seen early (first cycle) and at a relatively low dose.
and years since menopause was 6.2. All routes and concentrations of PC resulted in significant decrease in EPS from pretreatment and posttreatment EMB (P ⬍0.05). Both topical and vaginal placebo groups showed no difference in their EPS pretreatment and posttreatment EMB. Aversion to the application of PC was 35 % in the vaginal group versus 0% in the topical group. Conclusion: Topical and vaginal application of progesterone cream appears to have an antiproliferative effect on the endometrium. Patients preferred the topical application of progesterone cream.
Safety Profile: Transdermal Testosterone Treatment of Women After Oophorectomy* James A. Simon, MD
THIRD PRIZE PAPER Topical Progesterone Cream Has Antiproliferative Effect on Estrogen-Stimulated Endometrium James N. Anasti, MD St. Luke’s Hospital, Bethlehem, PA
H.B. Leonetti, MD, and K.J. Wilson, PhD Objective: Transdermal progesterone cream (PC) has become a popular alternative to hormone replacement therapy despite the lack of control trials. We designed a study to determine the effect of topical PC on the estrogen-stimulated endometrium of postmenopausal women. Method: Healthy postmenopausal women underwent an initial EMB after 14 days of oral estrogens only (0.625 mg conjugated equine estrogen [CEE]). Subjects then were randomized to 4 weeks of daily CEE with twice-daily application of vaginal or topical PC in various concentrations (placebo, 1.5%, 4%). A final EMB was performed after the 4 weeks of CEE and PC treatment. The EMBs were scored as to the degree of proliferation (EPS). The pretreatment and posttreatment EPS then were compared by ANOVA of ranks. Results: Fifty-eight women finished the study. The average age was 55.2 years, body mass index (BMI) was 26.7 kg/m2,
10S Tuesday Papers
Women’s Health Research Center, Laurel, MD
Norman A. Mazer, MD, PhD, and Kathryn Wekselman, RN, PhD Purpose: To evaluate the safety of two doses of testosterone (T) administered by investigational transdermal matrix patch to women with impaired sexual function after surgical menopause. Methods: Seventy-five women, aged 31–56 years, 1 to 10 years after TAH-BSO, received oral conjugated equine estrogens and, in random order, placebo, 150 g T, and 300 g T per day transdermally for 12 weeks each. Results: Serum-free and bioavailable T increased to normal values with both T treatments. Dihydrotestosterone and total T increased to above normal with 300 g T treatment, a finding related to higher than normal SHBG levels in women on oral estrogen. The hormones DHEA-S, estradiol, estrone, LH, FSH, and other safety parameters, hirsutism and acne scores, total cholesterol, HDL, LDL, triglycerides, hematocrit, platelets, WBC, bilirubin, AST, GGT, albumin, fasting glucose, insulin, heart rate, blood pressure, and hot flush frequency were not significantly affected by T treatment. Facial depilation rates (times/month) were similar for baseline (0.5), placebo (0.8) and 150 g T (0.7) and rose slightly for 300 g T (1.4). Adverse events during T and placebo treatments were comparable. One woman withdrew because of a skin reaction to the placebo patch; three others withdrew because of adverse events possibly or probably related to treatment.
* This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.
Obstetrics & Gynecology