20 Gynecology O B .GYN. NEWS • May 15, 2008 More Research Is Needed on Cardiac Events in LQTS Aromatase Inhibitors in PCOS Plunge After Menopause

BY BRUCE JANCIN Mr. Mathew reported on 1,624 BY MARY ELLEN SCHNEIDER clomiphene has yet to be done. The available data Denver Bureau women aged 20-70 years who New York Bureau are derived from very small studies, she noted. were enrolled in the Internation- In a prospective, randomized trial of 74 patients, C HICAGO — The high cardiac al Long QT Syndrome Registry, P HILADELPHIA — The jury is still out on researchers did not find a significant difference in event rate in women with long including 560 who were post- whether aromatase inhibitors could offer an al- pregnancy rates between women who received QT syndrome drops dramatically menopausal. The risk of the com- ternative to clomiphene in the treatment of in- clomiphene and those who received the aromatase post menopause, according to a bined end point of syncope, fertility associated with polycystic ovary syn- inhibitor letrozole (Fertil. Steril. 2006;86:1447-51). registry analysis. LQTS-related sudden death, or drome, based on results in two small clinical trials. However, the researchers found significantly low- This finding suggests that es- aborted cardiac arrest was 94% Aromatase inhibitors are on the horizon, Dr. er estrogen levels in the letrozole group on the day trogen is a major contributor to lower in the postmenopausal Andrea D. Coviello said at Endocrinology in the of human chorionic gonadotropin administra- arrhythmic events in women group. News, sponsored by Boston University, INTERNAL tion, Dr. Coviello said. with long QT syndrome (LQTS), The impact of menopause was MEDICINE NEWS, and FAMILY Another study, published Jehu S. Mathew reported at the particularly striking in women PRACTICE NEWS. Although There are significant online, compared the effica- annual meeting of the American with the LQT2 genotype. Their they have been approved for cy of letrozole and clom- College of Cardiology. annual combined event rate was use in breast cancer, they are concerns about fetal iphene among women who If this indeed proves to be the 11.86/year before menopause and still experimental for ovula- development problems in had failed to ovulate when case, the clinical implications 1.91/year after menopause. tion induction. Instead of taking 100 mg/day of could be profound. Planned fu- Among women with a QTc in- blocking the receptors cen- babies conceived by clomiphene citrate (Fertil. ture observational studies will terval of 500 msec or more, the trally in the hypothalamus women who were using Steril. 2008 January [Epub- look at LQTS patients who are on event rate was 9.68/year before and the pituitary, aromatase doi:10.1016/j.fertnstert. antiestrogen therapy—tamoxifen menopause and 2.35/year after- inhibitors completely block aromatase inhibitors. 2007.08.044]). Sixty-four pa- or aromatase inhibitors—for pre- ward. And among women with a estradiol production. Like tients were randomized to vention of breast cancer. If their history of syncope before age 20, clomiphene, aromatase inhibitor drugs are used receive either 7.5 mg/day of letrozole or 150 cardiac event rate turns out to be the event rate was 8.21/year pri- during the follicular phase, she said. mg/day of clomiphene. The researchers found substantially lower than expected, or to menopause, compared with The rationale for moving to aromatase in- that letrozole had better ovulation and pregnan- it could open the door to a whole 2.26/year postmenopause. hibitors is that this class of drugs is thought to cy rates compared with clomiphene. However, new form of cardiovascular pre- The genesis for this study ex- have fewer antiestrogenic side effects, including those results came as no surprise because the ventive therapy in the extremely amining the influence of a lower risk of ovarian hyperstimulation syn- women in the study were clomiphene resistant, high-risk population of women menopause on cardiac events in drome and a lower risk of multiple gestation. But Dr. Coviello said. So although it showed that with heritable LQTS, added Mr. LQTS was prior work establish- there are also significant concerns about fetal de- letrozole is not inferior in terms of ovulation, it Mathew, a fourth-year medical ing that females have a substan- velopment problems in the babies conceived by failed to make the case that aromatase inhibitors student at the University of tially higher cardiac event rate women who were using aromatase inhibitors, ex- outperform clomiphene. Rochester (N.Y.), in an interview. than have males with LQTS and plained Dr. Coviello, of the Endocrinology, Dia- Dr. Coviello stated she had no financial con- “The potential impact of those that women with LQTS have a betes, and Nutrition Section, Boston University flicts of interest to disclose. INTERNAL MEDICINE therapies on women with long QT higher event rate during the first School of Medicine. NEWS,FAMILY PRACTICE NEWS, and this newspa- syndrome is astounding if estro- 9 months post partum—a period A definitive study that would help physicians as- per are published by the International Medical gens are actually implicated in their of hormonal flux—than they do sess how aromatase inhibitors stack up to News Group, a division of Elsevier. ■ cardiac event risk,” he observed. during pregnancy. ■ Lamotrigine Aids Pain, Depression Urinary Incontinence Is Not In Women With Chronic Pelvic Pain More Severe With Bacteriuria S AVANNAH, GA . — Uri- session at the annual meeting BY KERRI WACHTER After baseline assessments, the women were nary incontinence symptoms of the Society of Gynecologic Senior writer titrated up to a therapeutic dosage of 400 mg/day do not appear to be more Surgeons. UDI6 and MESA lamotrigine over 8 weeks. This dosage was contin- prevalent or more severe in scores were compared be- B ALTIMORE — The anticonvulsant lamotrigine ued for weeks 8-12. Patients then were slowly dis- women with bacteriuria, tween women with and with- shows promise for reducing pain and improving continued from the drug over a 2-week period. A based on a study of 530 uro- out positive cultures. mood symptoms associated with chronic pelvic total of 31 women completed the 8-week titration gynecology patients seen at Uropathogen antibiotic sensi- pain, particularly in women with the vulvovaginal phase and 21 completed all 12 weeks of treatment. one institution. tivities were compared with subtype. Patients completed the McGill Pain Scale at each Dr. Mary P. Fitzgerald, of those of the general hospital In a study of 43 women with chronic pelvic pain, visit. Patients were also administered the Hamilton the obstetrics and gynecology population at that time. researchers at the University of North Carolina Depression Rating Scale. department at Loyola Univer- Uropathogens included Es- found that treatment with lamotrigine resulted in sig- The women completing 8 weeks of treatment sity in Chicago, and her col- cherichia coli (43), Klebsiella nificant reductions in total pain, overall pain inten- were aged 41 years on average and were predomi- leagues conducted a chart re- pneumoniae (13), Proteus sity, and depressive symptoms at 8 weeks, compared nantly white (95%). The average dosage in that pe- view of all new urogynecology mirabilis (4), Group B Strepto- with baseline. riod was 340 mg/day. Most of the women had the patients seen from March to coccus (1), and Citrobacter fre- There were slightly greater reductions in those vulvodynia/vulvar vestibulitis syndrome subtype December 2004. Scores from undii complex (4). Antibiotic measures at 12 weeks that achieved significance. The (17). The remaining women were evenly split be- the Urogenital Distress Inven- resistance profiles of the study, which was presented as a poster at the annu- tween diffuse abdominal pain (7) and neuropathic tory (UDI6) and Medical, Epi- uropathogens were similar to al meeting of the American Psychosomatic Society, pain (7). demiological, and Social As- those found in the general was funded by GlaxoSmithKline Inc., maker of The researchers also analyzed the data by chron- pects of Aging (MESA) hospital population. Lamictal (lamotrigine). ic pelvic pain subtype. Those with the vulvovaginal incontinence questionnaires “We suggest that inconti- Dr. Samantha Meltzer-Brody of the department of pain subtype (VVS) had significant reductions in were available. Urine cultures nence may not be a reliable psychiatry at the University of North Carolina, McGill total pain and visual analog scale overall pain had been obtained by catheter- symptom of bacteriuria in Chapel Hill, and her colleagues recruited women intensity scores at weeks 8 and 12. They also had a ization. Significant infection women attending a female from a tertiary care clinic. Participants had to have significant reduction in Hamilton Depression Rat- was considered to be present if urology/urogynecology clin- pelvic pain for at least 6 months. Women were ex- ing Scale scores at 12 weeks. However, the investi- at least 10,000 colonies of ic,” the researchers wrote. cluded if they had active systemic disease or sub- gators noted in the poster that “VVS patients have uropathogen were present. Dr. Fitzgerald reported that stance abuse, pelvic surgery in the previous 6 better mental health and decreased rates of sexual Of the 530 patients, 62 (12%) she had no relevant financial months, or initiation/change in psychiatric medica- and/or physical abuse history compared to women had positive cultures, Dr. relationships. tions in the previous month. with other chronic pelvic pain subtypes.” ■ Fitzgerald reported in a poster —Kerri Wachter