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An abstract of the article "The acceptability of a small intrauterine progestogen-releasing system for continuous combined hormone therapy in early postmenopausal women," by D. Sturdee, M. L. Rantala, J. C. Colau, Hp Zahradnik, and F. E. Riphagen is presented. It explains the reason why hormone therapy increases the risk of breast cancer. The objective of the study is to assess the acceptability of intrauterine progesterone releasing system for postmenopausal women.

Background: Homeopathic medicines have a place among the non-hormonal therapies for the treatment of hot flashes during the menopause., Objective: The objective of this study was to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women., Study Design: This was a multicenter, randomized, double-blind, placebo-controlled study carried out between June 2010 and July 2011., Setting: The study was conducted in 35 active centers in France (gynecologists in private practice)., Patients: One hundred and eight menopausal women, ≥ 50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥ 5 hot flashes per day with a significant negative effect on the women's professional and/or personal life., Intervention: Treatment was either BRN-01 tablets, a registered homeopathic medicine containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or identical placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrollment and was continued for 12 weeks., Main Outcome Measure: The main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded., Results: One hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01., Conclusion: BRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication. Trial registration number (EudraCT): 2009-016959-21.

Growing evidence indicates that androgens play a positive role in follicle proliferation and growth. Hence, many authors have assumed that androgen supplementation in women with poor ovarian reserve might improve the number of antral follicles available for ovarian stimulation. As androgen administration may become more frequently used in reproductive medicine, this study aimed at describing the histological changes observed in the genital tract and the breast of female-to-male (FTM) transsexuals. A pathological analysis of the genital tract of 112 FTM subjects who were given androgen for at least 6 months before hystero-salpingo-oophorectomy was performed. In addition, 100 bilateral mastectomies were performed, allowing a study of the breast tissue. Mean ovarian volume was increased, with histological characteristics of polycystic ovaries (PCO), defined as >12 antral follicles per ovary, observed in 89 patients (79.5%). Endometrial atrophy was observed in 45%. Breast examination revealed marked reduction of glandular tissue and increase of fibrous connective tissue in 93%, without atypical hyperplasia or carcinoma. The present data confirms and expands the putative associations between long-term androgen administration and abnormalities in ovarian architecture with macroscopic and microscopic characteristics of PCO, increased risk of endometrial atrophy and fibrotic breast tissue with marked glandular reduction., (Copyright (c) 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: This follow-up study was planned to establish the frequency with which women miss their contraceptive pill, and to observe their behavior when they forget it. In those women who changed from a continuous cycle to an interrupted type of cycle, or vice versa, the study also aimed to evaluate the impact of this change on the pattern of omission of pills., Methods: The longitudinal, prospective cohort study included healthy women of child-bearing age for whom a change of pill was being prescribed by their gynecologist. Data were recorded during the 6 months preceding inclusion in the study, and for the 6 months of follow-up; the women were asked to complete a diary in which they recorded the number and exact times of pill omission, and their behavior at each omission., Results: A total of 617 gynecologists included 3316 women into the study; of these, a group of 2418 (73%) revisited the same gynecologist at follow-up. The groups who either visited the same or a different gynecologist were similar with respect to age, oral contraception type, omission type and frequency. A large non-compliance rate and women's difficulties in maintaining safe contraception after missing a pill were observed in the group with follow-up. Women were never risk-free when they missed a pill; they turned to numerous sources for discordant or conflicting information; 15% of 'not-forgetting' women at the pre-inclusion cycle recorded at least one omission at the last cycle of the 6-month follow-up period. Omission fluctuations during the observational period make it difficult to designate 'forgetful' or 'non-forgetful' classes of women. Administration of the pill in a continuous cycle, and probably 'study' and 'auto-questionnaire' effects, contributed to an improvement in compliance. In the group taking the continuous cycle pill, the omission number slightly decreased, particularly on the first day and week of the cycle, irrespective of the initial cycle type., Conclusions: The importance of the phenomenon of non-compliance rate is confirmed as well as women's difficulties in knowing how to maintain contraceptive safety. The continuous cycle regimen is likely to improve women's compliance during the critical period of the cycle.

Objective: To assess the acceptability, ease of insertion, tolerance and associated bleeding of a novel intrauterine progestogen-releasing system, combined with transdermal estradiol, in postmenopausal women., Design: An open non-comparative study of 294 postmenopausal women with an intact uterus at 27 centers in six countries., Method: All subjects had requested treatment for menopausal symptoms and had received transdermal estradiol 50 microg/day by patch and an experimental intrauterine system (MLS) releasing levonorgestrel 10 microg/day. Details of the insertion were recorded and subsequent bleeding, side-effects and adverse events were documented on a daily diary. Endometrial thickness was measured by transvaginal ultrasound scan prior to insertion of the MLS and after 12 months. The study is of 3 years duration. This report summarizes the results after the first year., Results: The median age of the subjects was 52.6 years (range 41.7-59.6 years), 90% were within 3-5 years of menopause and 78% had previously used hormone therapy (HT). The MLS was inserted at the first attempt in 297/294 (94%) subjects and was facilitated by dilatation of the cervical canal in 65 (22%) subjects. Local anesthesia was given to 30 (10%) subjects. Of the 17 with a failed first insertion, two subjects did not want a second attempt, in 14 a second attempt succeeded, facilitated by cervical dilatation in seven and local anesthetic in three subjects. There was one failed insertion. Investigators rated 80% of first insertions as easy, 14% as slightly difficult and 6% as very difficult. The second insertion was easy in 9/15 subjects, slightly difficult in 4/15 and very difficult in one (data from one subject missing). During insertion, 34% subjects had no pain, 49% said it was mild, in 15% it was moderate and in 2% the pain was severe. At 12 months, one MLS had been expelled. Spotting was the most common form of bleeding and this decreased from a median of 9 to 0 days at 4 months, although 10% of subjects continued to report spotting up to 12 months. Bleeding days were few and mainly in the first 2 months. At the end of month 11, 66.8% were amenorrheic and 87% non-bleeding. Only nine subjects discontinued because of bleeding. There was no correlation between the bleeding profiles and number of years since menopause, previous HT use or body mass index. The median endometrial thickness at entry to the study (without HT) was 2.6 mm and 3.4 mm at 12 months. Of the adverse events, after the pain associated with insertion, headache was the next most common at 13.3% and mastalgia was experienced by 7.8% of subjects. Overall, the dropout rate was low at 28 subjects (9.5%). There were favorable changes in the serum lipid profile consistent with the effects of estradiol and suggesting minimal attenuation by the intrauterine progestogen. Conclusion This interim report of a 3-year study has confirmed that the menopausal levonorgestrel intrauterine system is easy to insert and is well tolerated by postmenopausal women.

Objectives: To determine the number of times women failed to take their oral contraceptive medication and their behavior in response to a missed pill. Another objective was to determine the potential benefit provided by a continuously administered oral contraceptive compared with an oral contraceptive involving a pill-free interval during a 6-month period., Methods: Healthy women were enrolled in a cohort study; their contraceptive practices were followed by their gynecologists. Data were collected at inclusion using cross-sectional method with retrospective data collection for the previous 6 months and, more specifically, on their previous or their current menstrual cycle. Women on the pill were asked to specify the number of times and precise time at which they missed one or more pills and what they did in response to missing a pill., Results: A total of 617 gynecologists enrolled and followed 3316 patients from six geographic areas throughout France. The mean age of patients was 30 years. Duration of oral contraceptive use was 8 years. During their previous cycle, 23% of women (n = 737) missed a pill at least once. Among women on the pill involving a treatment-free interval, 42% of instances of missing a pill occurred during the first week following the treatment-free interval. In response to missing a pill, patients read the product information leaflet (39%) or asked someone's advice (28%), mainly their gynecologist (63%) or their family physician (18%). Almost one-third of women did not take any specific measures., Conclusions: Patients on a discontinuous oral contraceptive regimen tended to miss a pill during the first week of treatment. Prescription of a continuous regimen without a treatment-free interval may improve compliance.

Objective: The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug., Study Design: In this multinational, double-blind, parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were randomly assigned to receive either 300 microg/d intranasal 17beta-estradiol (S21400) or 2 mg/d oral micronized estradiol, plus the appropriate placebo, for 24 weeks. All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle. Adjustment of intranasal dosage was permitted from week 14 on. The primary efficacy criterion was the Kupperman index at week 14, with a predefined limit of equivalence of 4., Results: Kupperman index scores improved similarly in the 2 groups, from 28.4 +/- 6.2 to 10.0 +/- 8.6 (mean +/- SD) for S21400 and from 28.1 +/- 6.0 to 8.9 +/- 8.0 for oral therapy, with a difference between groups at week 14 of 1.1 +/- 0.6 (90% confidence interval, 0. 0 to 2.2). This was below the predefined equivalence limit of +4 for statistical noninferiority (P <.001). The daily number and intensity of hot flushes decreased similarly in the two treatment groups. Withdrawal bleeding was 20% less frequent with intranasal therapy (90% confidence interval, 12.5 to 27.6). Severe mastalgia was less frequent in the S21400 group (1.0%) than in the group with oral therapy (5.2%; P <.01). Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400. The same number of patients required dose adaptation in the 2 groups (approximately 20%)., Conclusion: Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms, with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect.

Objective: To evaluate comparatively the acceptability and safety of a new pharmaceutical form of benzalkonium chloride, the vaginal capsule, with the pessary form., Methods: Eighty-nine women were randomized to receive either a benzalkonium chloride vaginal capsule or a benzalkonium chloride pessary prior to sexual intercourse according to an open cross-over design over a 2-month study period., Results: The discomfort caused by delayed leakage or discharge was mild. The mean scores for subjective signs (burning, itching, vulvar pruritus) were also mild and were comparable for the two formulations. The capsule appeared to be slightly superior to the pessary regarding discomfort caused by immediate discharge or leakage, ease of use and acceptance by the woman's partner. Local safety was generally good. Adverse events consisted chiefly of vulvar pruritus and a vaginal or vulvar burning sensation, with a higher incidence being associated with the pessary than the capsule. All symptoms regressed spontaneously after the end of treatment., Conclusions: This study demonstrated good acceptability and good local safety for the benzalkonium chloride vaginal capsule. It is essential to take these parameters into consideration in the evaluation of any local spermicidal contraceptive, since they play a large part in compliance with, and thus in the efficacy of, the product under assessment.

Objective: Our purpose was to study the correlation between maternal serum human chorionic gonadotropin levels measured at 15 to 18 weeks of amenorrhea and pregnancy-induced hypertension, preeclampsia, and small-for-gestational-age neonates., Study Design: Prospective trisomy 21 human chorionic gonadotropin screening data from 5776 patients were examined in a retrospective investigation of the relationship between human chorionic gonadotropin and pregnancy-induced hypertension (234 cases), preeclampsia (34 cases), and small-for-gestational-age neonates (238 cases)., Results: Maternal serum human chorionic gonadotropin (multiples of the median) was higher in the three populations with pathologic disorders. This difference was statistically significant in patients with small-for-gestational-age neonates (p < 0.0163) and preeclampsia (p < 0.0001) but not in those with pregnancy-induced hypertension. In the preeclampsia subgroup, with a cutoff value of 2 multiples of the median, specificity was 32% and sensitivity was 10%; with a cutoff value of 1 multiples of the median, specificity was 100% and sensitivity was 50%., Conclusion: High maternal serum human chorionic gonadotropin levels at 15 weeks are related to a risk for preeclampsia. Depending on the human chorionic gonadotropin cutoff value, 32% or 100% of preeclampsia patients would be selected. The usefulness of preventive aspirin treatment from the fifteenth week needs more investigation in a larger multicenter study of preeclampsia.

Twenty-five healthy women in labour received morphine 1-1.75 mg in normal saline intrathecally. The residual pain was evaluated on a scale from 0 to 5 at 10 min (score 2.5) and at 25 min (score 1.5). After delivery the maternal and fetal plasma morphine concentrations were measured by radioimmunoassay in 14 parturients. Twenty-three women of 25 had vaginal deliveries, 20 of them without forceps. The maternal and fetal plasma concentrations of morphine were 6 ng ml-1 or less. The intrathecal (but not extradural) administration of morphine is effective and could provide an interesting alternative for pain relief in labour.

The results of an experimental and clinical study on the benzydamine binding and distribution in vaginal mucosa are presented, employing benzydamine solution for gynaecological use. When applied first to rats, the mean amount of the drug in their vaginal mucosa became 3.65 +/- 2.99 micrograms/g of fresh tissue with a significant difference between control and treated animals, without detectable amounts in the plasma. When applied to humans, the mean amount of benzydamine assayed in 17 specimens of vaginal mucosa was 9.72 +/- 6.24 micrograms/g. It was greater than the range of animal anti-inflammatory concentration (2-8 micrograms/g) established by pharmacological studies on this drug and justified the local benefits from benzydamine treatment of vaginal inflammation. Benzydamine assayed in seven volunteers with healthy vaginas showed that the drug cannot be detected in the plasma.

102 patients at high risk of pre-eclampsia and/or fetal growth retardation were randomly allocated to treatment with 300 mg dipyridamole and 150 mg aspirin daily from 3 months' gestation onwards (group A) or to the control group (group B, no treatment). Group A was twice as likely as group B to have a normal pregnancy. Pre-eclampsia occurred in 6 patients in group B and none in group A. Major complications (fetal death or severe growth retardation) occurred in 9 patients in group B and none in group A. Platelet count and plasma volume were significantly higher in group A than in group B throughout pregnancy. The treatment did not produce serious adverse effects. Antiplatelet therapy given early in pregnancy to high-risk patients may thus protect against pre-eclampsia and fetal growth retardation.