Philip M. Hahn

Lasting response to ovariectomy in severe intractable premenstrual syndrome

A total of 14 women with severe premenstrual syndrome unresponsive to conservative medical therapy were treated with danazol in doses sufficient to suppress cyclic ovarian steroidogenesis. In each case medical ovarian suppression resulted in complete relief from symptoms. For ongoing symptom relief, each woman elected to undergo bilateral ovariectomy and concomitant hysterectomy. Both medical ovarian suppression and ovariectomy with low-dose conjugated estrogen therapy afforded lasting relief from cyclic symptoms of premenstrual syndrome and a corresponding improvement in overall quality of life. We conclude that cyclic ovarian steroidogenesis is a powerful determinant for the expression of premenstrual symptomatology. Ovariectomy with low-dose estrogen replacement is an effective alternative for the woman with debilitating premenstrual syndrome who does not respond to conventional interventions.

A double-blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome

Rigorous criteria were used to select women with severe premenstrual syndrome for inclusion in an 8-month double-blind placebo-controlled clinical trial of progesterone vaginal suppositories. Following a control month without treatment, progesterone (200 mg in polyethylene glycol base) or placebo was self administered twice daily by vaginal suppository for a minimum of 12 days before the onset of menstruation for 3 months. Crossover to the opposite medication for a further 3 months was followed by a final control cycle without treatment in month 8. Physician contact was minimized throughout the study to avoid any possible positive effects of psychological support which may have confounded past investigations. Detailed self-report questionnaires were completed every 3 days for the duration of the study. Although the attrition rate was high, 20 women completed the trial and their records are analyzed here. The results of this trial indicate that the response to vaginal progesterone in these dosages is, at best, marginal and not significantly different from response with placebo use.

A randomized, placebo-controlled, crossover trial of danazol for the treatment of premenstrual syndrome.

To investigate whether danazol is more effective than placebo for the treatment of premenstrual syndrome (PMS), we conducted a randomized, double-blind, crossover study comparing three successive cycles of danazol (200 mg bid) to three cycles of placebo. Thirty-one women meeting rigorous criteria for a diagnosis of severe PMS over two pretreatment cycles were enrolled; 28 of these subjects completed at least one cycle of treatment with symptom recordings, which were entered into the analysis. A significant period effect confounded the planned within-subject analysis and therefore, the main treatment comparisons were confined to the first period only. Symptom scores on the Premenstrual Tension Self-Rating Scale (PMTS), Beck Depression Inventory (BDI), and a Visual Analogue Scale (VAS) were compared for the premenstrual week in the last cycle of treatment. For the 16 patients on danazol, scores on the PMTS decreased by an average of 14.0 (10.7) (standard deviation) points from a baseline of 25.4 (5.6) points. For the 12 patients on placebo, PMTS scores decreased by an average of 3.6 (9.5) points from a baseline of 23.5 (5.8) points (14.0 vs. 3.6; p = .0133, unpaired t-test). Seven (43.8%) of the subjects on danazol achieved a clinically relevant reduction of symptoms into the asymptomatic range (PMTS scores < or = 5) as compared to one (8.3%) of the subjects on placebo. Thus, danazol (200 mg bid) provided greater relief from severe PMS during the premenstrual week than did placebo.

Maternal Hemodynamics After Oxytocin Bolus Compared With Infusion in the Third Stage of Labor: A Randomized Controlled Trial

OBJECTIVE: To assess the effects of oxytocin bolus or infusion on maternal hemodynamics in the third stage of labor. METHODS: In a randomized, double-blind, double-dummy fashion, 99 women received an intravenous oxytocin bolus (10 IU push) and 102 women received an infusion (10 IU in 500 mL saline at 125 mL/h) at delivery of the anterior shoulder. Mean arterial pressure and heart rate were measured every minute for 10 minutes, then every 5 minutes for the next 20 minutes. These serial measurements were analyzed using a 2-factor analysis of variance for repeated measures. RESULTS: Serial mean arterial pressure measures varied significantly between groups (interaction effect, P = .002). Mean arterial pressure (± standard deviation) nadirs were reached after 10 minutes, 80.9 (± 11.0) mm Hg in the bolus group compared with 77.0 (± 12.1) mm Hg in the dilute infusion group. The mean difference (95% confidence interval) between groups was 4.0 (0.7–7.2) mm Hg. Serial heart rate measures also varied between groups (interaction effect, P < .001). Mean heart rate (± standard deviation) peaked 1 minute after the oxytocin infusion, 115 (± 27) beats per minute (bpm) in the bolus group compared with 109 (± 21) bpm in the dilute infusion group. The mean difference (95% confidence interval) between groups was 6.6 bpm (−0.1 to 13.3). The dilute oxytocin infusion group experienced a greater mean estimated blood loss (423.7 mL compared with 358.1 mL, P = .029, t test), increased use of additional oxytocics (35.3% compared with 22.2%, P = .044, Fisher exact test) and a greater drop in hemoglobin (admission minus postpartum) (17.4g/L compared with 11.4g/L, P = .002, t test) compared with the oxytocin bolus group. CONCLUSION: Bolus oxytocin of 10 IU is not associated with adverse hemodynamic responses and can safely be administered to women with intravenous access in the third stage of labor for postpartum hemorrhage prophylaxis. LEVEL OF EVIDENCE: I

Menopausal-like hot flashes reported in women of reproductive age

OBJECTIVE To report the occurrence of menopausal-like hot flashes in women of reproductive age (18-45 years). DESIGN Observational, prospective cohort study with a retrospective survey component. SETTING Tertiary care premenstrual syndrome (PMS) clinic and university campus. PATIENT(S) Patients with confirmed PMS (n = 157) were compared with those with chronic menstrual cycle-related symptoms (n = 27). Women without menstrual cycle-related symptoms were solicited as controls (n = 58). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The frequency of episodes of chills and sweats and the magnitude of menstrual cycle-related symptoms were recorded over one cycle using the Prospective Record of the Impact and Severity of Menstrual Symptomatology (PRISM) Calendar. Characteristics of the episodes of chills and sweats were ascertained by a retrospective questionnaire. RESULT(S) In each group, the frequency of episodes of chills and sweats closely patterned the mean daily PRISM Calendar scores. At least one episode of chills and sweats was reported by 83.4% of the PMS group and 81.5% of the chronic group compared with 43.1% of the control group. The mean (+/-SD) number of episodes per cycle was 5.6 +/- 4.9 for the PMS group and 9.5 +/- 9.1 for the chronic group compared with 1.2 +/- 2.0 for the control group (the difference between all means was statistically significant). CONCLUSION(S) Episodes of chills and sweats similar to menopausal hot flashes were commonly reported by women with cyclic and chronic menstrual cycle-related symptoms.

A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparint

Objective: To compare the efficacy of heparin-saturated oxidized regenerated cellulose absorbable adhesion barrier, Interceed (TC7; Johnson and Johnson Medical Inc., New Brunswick, NJ) to oxidized regenerated cellulose alone for the prevention of postoperative adhesions. Design: Clinical trial. By random assignment, one ovary was wrapped in oxidized regenerated cellulose, and the contralateral ovary was wrapped in oxidized regenerated cellulose saturated with a heparin solution (1,000 U/mL). Patient(s): Forty women with defects on both ovaries due to adhesiolysis and/or ovarian cystectomy. Main Outcome Measure: Adhesion formation and raw ovarian surface area were assessed at second-look laparoscopy 10 days to 16 weeks later. Result(s): At the second-look laparoscopy, adhesions were present on 52.5% (21/40) of the ovaries treated with oxidized regenerated cellulose plus heparin and in 65% (26/40) of the contralateral ovaries treated with oxidized regenerated cellulose alone. For ovaries treated with oxidized regenerated cellulose plus heparin, the raw surface area was reduced from 9.41 ± 1.27 cm 2 (mean ± SE) at laparotomy to 1.33 ± 0.52 cm 2 at second-look laparoscopy. The corresponding figures for ovaries treated with oxidized regenerated cellulose alone were from 10.24 ± 1.08 to 1.92 ± 0.54 cm 2 , respectively. The mean difference between the reductions in raw surface area (85.9% for oxidized regenerated cellulose plus heparin; 81.3% for oxidized regenerated cellulose alone) was not significantly different from zero (difference = −0.24 cm 2 ; 95% confidence interval=−2.56 to 3.04). Conclusion(s): Adding heparin did not enhance significantly the adhesion-reducing capacity of oxidized regenerated cellulose adhesion barrier when applied to ovarian surfaces after cystectomy and/or ovariolysis at laparotomy. This conclusion is subject to the possibility of a type II error.

The Acceptance of Medical Students by Women With Gynaecology Appointments

OBJECTIVES To determine the proportion of women unwilling to see medical students for their upcoming gynaecologic appointments and to determine whether information about medical student training could influence their decisions. METHODS Questionnaires were mailed to 1230 women with outpatient gynaecology specialist appointments. The women were asked if they would be willing to see a medical student at their upcoming appointment. Those who declined were asked to indicate the reason(s) for their decision. After reading the surveys information section on medical students, patients who initially rejected student involvement were asked if they would reconsider. Mean differences were analyzed with t tests and associations with Fisher exact tests. RESULTS Thirty percent (367/1230) of the surveys were returned and analyzed. The mean age was 48.4 years (range 17-90). Fifty-three percent (189/358) reported a positive past experience with medical students, and 7% (25/358) reported a negative past experience. Twenty-six percent (96/367) indicated that they would not be willing to be seen by a medical student. Sixty-three percent (60/96) did not wish to have a gynaecologic examination performed by a student. One-third (32/96) identified this as a concern particularly if the examination involved a male student. After reading the information section of the survey, 17% (16/96) of the respondents who initially indicated they were unwilling to see a medical student indicated that they would reconsider. Those who would reconsider were younger than those who remained unwilling (mean age 41.9 vs. 52.1 years, P= 0.045). CONCLUSION The information about medical students embedded in our survey positively influenced one in six unwilling patients to reconsider and accept medical students as part of their health care team.

Photodynamic ablation of early pregnancy in the rat with 5-aminolevulinic acid : a potential new therapy for tubal ectopic pregnancy in the human

OBJECTIVE To determine whether systemic 5-aminolevulinic acid (ALA) could produce photosensitization and photodynamic ablation of early pregnancy in the rat. SETTING A conventional laboratory setting. PATIENTS Female Sprague-Dawley rats, weighing 220 to 275 g at the time of breeding. INTERVENTIONS Rats at 10 days of gestation were injected IV with saline, 20 or 200 mg/kg ALA. Three hours later, the abdominal cavity was opened to record the number of fetuses in both uterine horns. One or both uterine horns were exposed to photoactivating light at 630 nm for 0, 5, 15, or 30 minutes. MAIN OUTCOME MEASURES Mean fetal survival rate was determined 7 days after treatment. RESULTS The mean +/- SEM fetal survival rates in groups (n = 6) treated with saline, 20 or 200 mg/kg ALA followed by 30-minute light exposure were 90.8% +/- 2.8%, 16.0% +/- 4.9%, and 0%, respectively. The mean +/- SEM fetal survival rates in groups (n = 6) treated with 200 mg/kg ALA followed by 0-, 5-, 15-, or 30-minute light exposure were 71.3% +/- 11.8%, 8.9% +/- 6.2%, 0.9% +/- 1.3%, and 0%, respectively. CONCLUSIONS We conclude that systemic ALA followed by transmural exposure to photoactivating light (630 nm) results in resorption of early pregnancies in the rat. This approach could potentially be developed as a new treatment for human ectopic pregnancy.

Treatment of Menorrhagia with Tranexamic Acid

Abstract Objective: to evaluate the efficacy of tranexamic acid for essential menorrhagia. Subjects: women 18 to 45 years of age with a complaint of heavy menstrual bleeding. Design: two pre-treatment baseline cycles were compared to three consecutive treatment cycles of tranexamic acid (one g taken orally every six hours throughout days one to three of each menstrual period). Main outcome measurements: menstrual blood loss using the pictorial blood loss assessment chart (PBAC) and blood haemoglobin (g/L). Results: all eleven patients recruited into the study had objective evidence of menorrhagia, defined as an average PBAC score of greater than or equal to 100 over two pre-treatment cycles. The median difference between baseline and treatment PBAC scores of 96.8 was statistically significant (p = 0.003, Wilcoxon Signed Ranks Test, Range=32.8 to 432.8). This represented a median 47.4 percent decrease in menstrual blood flow. Four patients recorded a mean PBAC score of less than 100 for the three treatment cycles, indicating a return to normal menstrual flow of less than 80 mL. Three patients were anaemic upon entry into the study as defined by WHO (haemoglobin Conclusions: Tranexamic acid is an effective, well-tolerated medication for the treatment of essential menorrhagia and may be utilitized as a first line therapy.

Gender Preference for a Female Physician Diminishes as Women Have Increased Experience With Intimate Examinations

OBJECTIVES To determine the importance of seven statements encouraging medical student participation in the health care team with respect to the effect they would have on a womans decision to allow a medical student to participate in an intimate physical examination, and to explore factors associated with gender bias. METHODS Questionnaires were administered to women attending outpatient clinics in obstetrics and gynaecology at Kingston General Hospital and to students at two local secondary schools. RESULTS Responses from 683 clinic patients and 192 secondary school students were analyzed. The mean age (range) was 42 years (17- 85) and 16 years (15- 22) for the respective samples. More clinic patients rated each of the statements as important or very important than did students (P < 0.01, Fisher exact tests). The largest differences between the sample groups were seen for the statements pertaining to the potential for enhanced understanding (81.0% vs. 60.2%), quality of health care (87.4% vs. 69.8%), and affording medical students the opportunity to participate (92.7% vs. 77.0%); 72.8% (485/666) of clinic patients reported they would accept an intimate examination by a medical student of either gender, compared with 32.1% (61/190) of secondary school students, and 22.2% (148/666) of clinic patients indicated they would only accept a female student compared with 55.3% (105/190) of secondary school students. The proportion of students preferring female medical students was inversely related to the number of previous breast or pelvic examinations (P = 0.031, chi-square test for trend). CONCLUSIONS Educational statements designed to encourage women to allow students to participate in their medical care had less effect on the secondary school students than on the women in a clinic setting. Although secondary school students express a preference for female physicians, it appears that with increasing experience with intimate examinations other factors take precedence in determining choice of health care provider.