14 REPRODUCTIVE ENDOCRINOLOGY JANUARY 2009 • CLINICAL ENDOCRINOLOGY NEWS Topical Tamoxifen Promising for Mastalgia BY BRUCE JANCIN al, of Cardiff (Wales) University. afimoxifene to their breasts daily for 21 dose showed less robust albeit favorable Denver Bureau Oral tamoxifen, bromocriptine, dana- days. At steady state, achieved after 2 trends on all end points, he continued. zol, and progestins have demonstrated weeks of therapy, mean plasma 4-hy- In an interview, Dr. Goyal said he has S AN A NTONIO — Afimoxifene, a efficacy in treating cyclic mastalgia; how- droxytamoxifen levels were just 1/18 of had some success in using oral tamoxifen novel tamoxifen gel applied directly to ever, their systemic side effects render those measured in 19 healthy controls in men with gynecomastia. He plans to the breasts, performed favorably as top- them poorly suited for long-term treat- taking 20 mg/day of oral tamoxifen. study topical afimoxifene for this condi- ical therapy for moderate to severe cyclic Based upon those encouraging find- tion in a placebo-controlled trial. mastalgia in premenopausal women in a After 4 cycles, ings, Dr. Goyal and colleagues next carried Prevention of breast cancer is an ex- phase II clinical trial. pain intensity out the phase II trial involving 127 pre- citing potential application for the topical Although the topical antiestrogen’s de- was 64% lower menopausal women with moderate to selective estrogen-receptor modulator. veloper, ASCEND Therapeutics Inc., in women on severe cyclic mastalgia. They were ran- “The main reason why some women plans to seek an initial indication for afimoxifene than domized to placebo or either 2 mg or 4 mg and some physicians are reluctant to use cyclic mastalgia, there also is strong in- in the placebo of afimoxifene daily for 4 menstrual cycles. oral tamoxifen, even though we know terest in developing afimoxifene as a group. Significant differences in efficacy be- from [a previous] study that it works, is treatment for male gynecomastia as well tween the 4-mg dose and placebo were because of side effects. If we can show as for breast cancer chemoprevention, DR. GOYAL documented after 2 cycles. After 4 cycles, afimoxifene works to prevent breast can- Dr. Amit Goyal said at the San Antonio mean pain intensity measured on a visual cer as well as oral tamoxifen, I think that Breast Cancer Symposium. ment of a chronic problem. In contrast, analog scale for the 7 worst days per cy- would be an important advance,” Dr. Afimoxifene is 4-hydroxytamoxifen, a transdermal afimoxifene is highly effec- cle was 64% lower in women on 4 Goyal said. potent metabolite of tamoxifen, in a pro- tive within the breast yet has very low mg/day of afimoxifene than in the place- The mastalgia trial was supported by prietary hydroalcoholic gel. Its binding systemic levels, thus reducing the risk of bo group. Physician global assessments ASCEND Therapeutics. Dr. Goyal indi- affinity for the alpha– and beta–estrogen systemic toxicities, he continued. of breast nodularity and tenderness cated he has received research funds receptors is two- to threefold greater In a pharmacokinetic study, 16 healthy showed reductions of 70% and 67%, re- from the company but has no other fi- than that of estradiol, explained Dr. Goy- premenopausal women applied 4 mg of spectively, relative to placebo. The 2-mg nancial involvement with ASCEND. ■ Inflammatory Bowel BMI Greater Than 25 May Increase Risk Disease May Speed of Miscarriage of a Normal Fetus Ovarian Follicle Loss BY SHARON WORCESTER preimplantation genetic diagnosis. S AN F RANCISCO — Inflammatory bowel dis- Southeast Bureau In addition to an increase in euploid miscarriage risk ease does not severely alter ovarian reserve but may based on BMI, a trend toward increased risk among accelerate loss of primordial follicles in those aged S AN F RANCISCO — The risk of miscarriage of a ge- women with polycystic ovary syndrome, compared 30 years and older, study results showed. netically normal fetus is significantly increased in over- with those without PCOS, was observed (48% vs. 39%, The investigators measured anti-müllerian hor- weight women, compared with normal weight women, respectively), but the difference did not reach statistical mone—a reliable hormonal marker for evaluating the findings of a retrospective case-control study of 204 significance. Also, no significant differences in euploid ovarian reserve independently of the menstrual cy- miscarriages suggest. miscarriage were seen based on insulin resistance sta- cle—in 44 women aged 20-41 years who had IBD The rate of euploid miscarriage among 204 first tus. However, because all but one of the women with and were in clinical remission after infliximab treat- trimester missed abortions that occurred between 1999 insulin resistance were on insulin-lowering therapy at ment for either Crohn’s disease (37 patients) or ul- and 2008 in women at a single center was 53% in those the time of conception, the conclusions in these popu- cerative colitis (7 patients). with a body mass index of 25 or greater, compared with lations are limited, Dr. Landres noted. The hormone levels were compared with those 37% in those with a BMI of less than 25. The difference The findings, which suggest that BMI over 25 is a risk of 163 age-matched women undergoing in vitro fer- was statistically significant, Dr. Innes V. Landres re- factor for euploid miscarriage, are important, given the tilization who had a normal ovarian response to ported at the annual meeting of the American Society fact that BMI (unlike age) is a modifiable risk factor. Al- controlled ovarian stimulation (5-15 oocytes re- for Reproductive Medicine. though the study is limited by its retrospective nature, trieved) and a normal serum anti-müllerian hor- The mean age of the women in both groups was the lack of power, and multiple confounders for which the mone level (>1.5 mcg/L). same (34 years). Those over age 39 years were exclud- investigators could not control, it is nonetheless im- The anti-müllerian hormone levels did not differ ed because of the increased risk of miscarriage in portant that elevated BMI be identified as a risk factor significantly overall between the IBD and control women with advanced maternal age, noted Dr. Landres, for euploid miscarriage, and that women with elevated patients (2.72 vs. 2.12 mcg/L), Dr. Thomas Fréour a chief resident in obstetrics and gynecology at Stanford BMI be counseled about the importance of lifestyle reported in a poster at the annual meeting of the (Calif.) University. modification. Also, although more study is needed on American Society for Reproductive Medicine. The groups also were similar in types of assisted re- the effects of insulin-lowering medications in this pop- However, when the women were stratified by age productive technologies used and in pregnancy history. ulation, treatment should be considered. 30 years and older vs. age less than 30 years, the anti- The study was undertaken to explore the cytogenet- Additional study of the effects of BMI on endometrial müllerian hormone levels were found to differ in the ic results of miscarriages in relation to maternal weight dysfunction and miscarriage rates, as well as on the ef- older women, with those aged 30 years and older hav- and insulin resistance, Dr. Landres explained. fects of lifestyle modification, is needed, Dr. Landres ing lower levels than controls (2 vs. 2.96 mcg/L). The Both obesity and insulin resistance have been linked concluded. ■ levels in the younger patients remained comparable with spontaneous abortion and recurrent pregnancy in the patients and controls, said Dr. Fréour of the loss. Most spontaneous abortions are a result of fetal University Hospital Center of Nantes (France). aneuploidy, as was the case in 59% of patients overall Inflammatory bowel disease has been shown in in this study—67% in those over age 34 years, and 50% previous studies to be associated with female sub- in those 34 years and younger. There is some evidence, fertility, mainly through tubal dysfunctions, exten- however, that obesity predisposes women to euploid sive adhesions, or chirurgical consequences on miscarriage, and that there is an increased rate of spon- pelvic function, but alteration of ovarian reserve in taneous abortion even among obese women with ovum those with IBD had not been previously studied, Dr. donation. Fréour noted. For the current study, the medical records of women The findings suggest that in reproductive age with first trimester missed abortion, subsequent dilation IVION women 30 years and older who have IBD, a sub- and curettage, and karyotype analysis of the products S stantially accelerated loss of primordial follicles may of conception were reviewed. Among the patients ex- OMAN occur. This loss might be due to chronic inflam- cluded—other than those older than 39 years—were R mation or to IBD treatments, he noted. those patients with a history of diabetes, those using Elevated BMI should be seen as a risk factor for —Sharon Worcester steroids or narcotics, and those with donor eggs or euploid miscarriage, said Dr. Innes V. Landres. .