The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats.

There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F(0)) with reproductive parameters, and in the somatic cells of the resulting foetuses (F(1)) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: a 12-month, double-blind, parallel clinical trial.

OBJECTIVE: Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN: We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS: A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS: We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS: A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS: Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.

What is the seminal exposition among women requiring emergency contraception? A prospective, observational comparative study.

OBJECTIVES: The aim of this study is to determine the number of sperm present in the vagina of women presenting for EC after unprotected intercourse or a condom accident. STUDY DESIGN: A total of 69 women requesting EC were included in a prospective, observational and comparative study. The absence or presence and number of spermatozoa present were examined under light microscopy in endocervical and vaginal smears. An ethinylestradiol-levonorgestrel combination (100 mcg/500 mg for two doses, 12 h apart) was then prescribed. Twenty couples were taken as controls. RESULTS: In 25 (36.2%) of the 69 women, spermatozoa were not observed. In the women in whom sperm could be identified, there were no significant differences in the mean (range) sperm count in relation to the reason for requesting EC, i.e., 11.0 (0.03-149.8) for condom slippage or breakage, and 8.1 (3.9-55) for unprotected intercourse. In the group of controls the median (range) number of spermatozoa (32.5 (2.5-304) was significantly higher (p=0.04) than the observed in the study group. CONCLUSIONS: In one-third of the women presenting for EC, no sperm were identified in the vagina. When sperm were present, the number was much lower than that after intercourse among women wishing to conceive. The risk of an unwanted pregnancy is probably, therefore, lower for women who present for EC compared with that for women who truly have unprotected intercourse.

Cost-effectiveness analysis in the treatment of heavy menstrual bleeding in Spain.

OBJECTIVE: To compare the effectiveness and costs associated with first-line medical treatments for chronic heavy menstrual bleeding (HMB) in Spain. STUDY DESIGN: A cost-effectiveness analysis was conducted comparing the levonorgestrel-releasing intrauterine system (LNG-IUS) with the estradiol valerate/dienogest multiphase oral contraceptive (E2V/DNG), combined oral contraceptives (COC) and progestins (PROG). Study patients were fertile women diagnosed with HMB who initially wished to remain fertile. A Markov model based on reported clinical data and the opinion of a panel of experts was used. The time horizon of the analysis was 5 years. The analysis was conducted from the perspective of the Spanish National Health System (NHS), discounting both costs (€ 2013) and future effects at an annual rate of 3%. One-way sensitivity analyses and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: In the analysis at 5 years, the LNG-IUS was associated with a gain of 0.67, 2.22, and 3.53 symptoms free months (SFM) compared with E2V/DNG, COC and PROG, respectively. LNG-IUS contributed more quality-adjusted life months (QALM) than the other treatment alternatives (+1.74 vs. E2V/DNG, +3.33 vs. COC +3.53 vs. PROG). First-line LNG-IUS treatment resulted in savings of € 583, € 988, and € 1891 vs. E2V/DNG, COC and PROG, respectively. These cost benefits, coupled with the greater clinical benefits in terms of SFM and QALM, show that LNG-IUS is the dominant option (less costly and more effective). CONCLUSION: LNG-IUS is the medical treatment of choice and cost-saving option for the control of HMB in Spain.

Induced human gestational hypoprolactinemia: lack of action on fetal adrenal androgen synthesis.

To investigate the possible role of PRL in the control of fetal adrenal function, blood samples were collected from maternal peripheral and cord blood from six women at delivery, who had received treatment with bromocriptine (3.75--35 mg daily) for the entire gestation. A group of eight untreated parturients served as control. Parameters measured were PRL and dehydroepiandrosterone, the latter as an indicator of fetal adrenal function. PRL was significantly suppressed (P < 0.002), whereas dehydroepiandrosterone was not influenced by bromocriptine treatment. The results indicate that the control of fetal production of androgenic substrate by the adrenals is not specifically PRL dependent.

Pulmonary endometriosis: conservative treatment with GnRH agonists.

The lung is an infrequent location of extragenital endometriosis, an exceptional cause of hemoptysis or pneumothorax. Adequate management has not yet been well established. We present two cases of pulmonary endometriosis, parenchymal and pleural. The presenting symptoms were catamenial hemoptysis and pneumothorax, respectively, which were treated with GnRH analogues. The first patient received Buserelin (900 micrograms/day intranasally) for 6 months. After 15 months of normal menstrual activity, the symptoms reappeared. The patient was then treated with Triptorelin (3.75 mg/month intramuscularly) for 6 months and remains asymptomatic and menstruating 14 months after discontinuing treatment. The patient presenting with pneumothorax was treated with leuprolide (1 mg/day subcutaneously) for 6 months and is asymptomatic 1 year after stopping treatment. These results suggest that GnRH analogues may be an acceptable alternative to danazol in the medical management of pulmonary endometriosis.

Randomized comparison of intranasal and transdermal estradiol.

OBJECTIVE: To compare the efficacy and patient acceptability of intranasal versus transdermal 17 beta-estradiol (E2) delivery systems for postmenopausal symptoms. METHODS: Postmenopausal women were randomly assigned to intranasal 17 beta-E2, 300 microg daily (n = 176) or transdermal 17 beta-E2 (delivering 50 microg/day), two patches per week (n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. RESULTS: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups (P <.001). The difference between groups in the Kupperman Index score of -0.5 +/- 0.9 (95% confidence interval -2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P =.02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy (P <.001). Satisfaction was greater with intranasal therapy at week 16 (P <.001). CONCLUSION: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients' choice for long-term treatment.

Sperm recuperation and cervical insemination in retrograde ejaculation.

Seven infertile patients with retrograde ejaculation, in which spermatozoa could be recuperated from the postejaculation urine, were admitted to a sperm recuperation and cervical insemination program. A noninvasive method for sperm recuperation based on urine alcalinization and serial controls to time masturbation has been used. Insemination has been timed according to BBT charts and cervical mucus characteristics. Pregnancy has been obtained in the seven couples after one to eight treatment cycles.

Familial leiomyomatosis cutis et uteri (Reed's syndrome).

We report a large family with leiomyomatosis cutis et uteri. Sixty-four percent of the females were involved; 18% had only uterine myomas, 10% had only cutaneous piloleiomyomas, and 36% had both. Five patients (45%) had to have an hysterectomy before age 35. Management of female patients having leiomyomatosis cutis should include a periodical gynecological examination in order to rule out the presence of uterine myomas.

The role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception.

The effectiveness of postcoital contraception can only be estimated. The most commonly used method of calculation compares the expected pregnancy rate in the exposed population to the resultant pregnancies after treatment. Estimation of the fertile period and the day of ovulation are critical to calculate the expected pregnancies. The aim of this study was to improve the accuracy of calculations by evaluating the hormonal status on the day of contraceptive treatment. A total of 483 consecutive women requesting postcoital contraception was included in a prospective observational trial. A blood sample was obtained at the moment of consultation to measure serum luteinizing hormone, estradiol, and progesterone concentrations. An ethinylestradiol-levonorgestrel combination (100 micrograms/500 mg for two doses, 12 h apart) was then prescribed. The fertile period was estimated according to previous hormonal studies in the normal cycling population. Of 483 women, 64 (13.25%) women were excluded because they presented irregular menstrual cycles and 37 (7.6%) women were lost to follow-up. Two pregnancies occurred in the remaining 382 women. Following Wilcox's and Trussell's methods, 21.1 and 17.75 pregnancies should be expected, yielding an overall treatment effectiveness of 90.52% (95% confidence interval [CI] 62.58%-97.6%) and 88.73% (95% CI 55.93%-97.12%), respectively. Hormonal data were available in 356 women; 303 of whom presented with regular cycles. Hormonal information in this group restricted the number of exposed cases to 88 women. Of the women included in Trussell's method of analysis, only 51 (51.5%; p < 0.05) were at risk using hormonal data. Fifty-six percent (95% CI 34.9%-75.6%) of women with luteinizing hormone levels > 20 IU/L were not between days-1 and +1 of the cycle. Hormonal studies suggest that methods based on pregnancy risk calculated by cycle day do not faithfully reflect the real exposure.

A betamimetic drug and human fetal lung maturation.

In a double-blind and randomized study the administration of a betamimetic drug to the mother from week 33 to 35 produces a significant increase in amniotic fluid palmitic acid levels. We suggest that the administration of a betamimetic drug during pregnancy to the mother can be useful in producing an acceleration of the fetal lung maturation.

Neonatal respiratory distress syndrome (RDS) in cases of premature labor treated by betamimetic drugs.

In 87 premature labors, 31 were treated with betamimetic drugs. The incidence of RDS in the treated group has been lower than in the non-treated group, especially when gestational age was shorter than 35 wk and when newborn's weight was lower than 2000 g.

Postmenopausal androgen secreting ovarian tumour: pathophysiological implications; a case report.

Hyperandrogenism in women is usually accompanied by a disruption of the hypothalamic-pituitary-ovarian axis; however, the precise effect of chronically elevated androgens on this axis is poorly understood. We report a postmenopausal woman with a virilizing ovarian tumour in whom the effects of chronic testosterone secretion on the hypothalamic-pituitary axis was investigated. A 56-year-old woman was evaluated for hirsutism and hyperandrogenism of recent onset. Peripheral serum testosterone was high (19.4 nmol/l), while gonadotropins were below normal for a postmenopausal woman, FSH (19.7 IU/l) being higher than LH (10.3 IU/l). Four LH and 1 FSH pulse were detected over 4 h. A left intraovarian testosterone secreting tumour, shown by catheterization of the ovarian veins and containing imperfect crystalloids of Reinke, was excised. Postoperatively, peripheral testosterone became undetectable, while gonadotropins rose to normal postmenopausal values. This patient's LH/FSH ratio was less than 1, in contrast with other situations of chronic hyperandrogenism. This could be explained by the concomitant hypoestrogenic state, and/or the theoretical absence of inhibin. The interest of this case resides in that it constitutes an appropriate model for studying the effects of testosterone on LH and FSH secretion in the absence of the other two classically involved modulators, namely oestrogens and inhibin.

Increasing incidence of ovarian pregnancy.

This paper presents the results of a review of seven ovarian pregnancies occurring during an 11 year period (1976-1986). The prevalence of the disease is higher than that expected either for the number of deliveries or for all ectopic pregnancies. The presence of etiological factors such as pelvic inflammatory disease, previous abdominal surgery, endometriosis or use of IUD, is considered. Four of these cases presented in actual users of IUD and one in an infertile woman previously diagnosed of endometriosis. The clinical pattern was similar to that recorded for tubal ectopic pregnancies. The role of IUDs and other risk factors in the apparent increase in the number of ectopic pregnancies detected is discussed. Measures to increase accuracy in the detection of early ovarian pregnancies are proposed.

PIP: To investigate further the apparent increase in the incidence of ectopic ovarian pregnancy and its possible association with IUD use, the 7 such pregnancies recorded in the authors' Barcelona hospital practice in 1976-86 were reviewed. During this period, ectopic pregnancies accounted for 1 of every 141 deliveries, which ectopic ovarian pregnancies represented 1 in every 18 ectopic pregnancies. 6 of the 7 ectopic ovarian pregnancies occurred in recent years: 1 in 1984, 2 in 1985, and 3 in 1986. The patients' mean age was 31 years (range, 28-33 years). All cases displayed both ovarian and trophoblastic tissue within the same microscopic field, while the macroscopic appearance of the homolateral tube was normal. The clinical symptoms (predominantly abdominal pain and menstrual disturbances) and physical examination results (the presence of an adnexal mass and pain at the level of the Douglas pouch) in women with ovarian pregnancies did not differ from those in women with ectopic pregnancies. Echography was highly accurate in the detection and localization of early ovarian pregnancies. 2 of the risk factors considered--pelvic inflammatory disease and previous abdominal surgery--were not present in this series of 7 cases; a 3rd-- endometriosis--was reported in 1 case, making this the most apparent risk factor.

[Serum insulin and androgen concentrations in women with histories of gestational diabetes]. / Concentraciones séricas de insulina y andrógenos en mujeres con antecedentes de diabetes gestacional.

BACKGROUND: There is a certain degree of peripheral cell resistance to insulin in the physiopathology of gestational diabetes. These disturbances may persist following pregnancy giving place to secondary hyperinsulinism. Insulin exerts a trophic action on the ovary and favors the production of androgens. The aim of this study was to verify whether the patients diagnosed of gestational diabetes present androgenic alterations following pregnancy. The existence of a correlation between the values of insulin and androgens was analyzed. METHODS: Fifty-one patients were studied. The study group (n = 297) was composed of patients diagnosed of gestational diabetes during their last week of pregnancy. The control group (n = 24) included patients with normal carbohydrate tolerance. The basal values of insulin, glucose, androstenedione, testosterone and SHBG were determined in a postmenstrual phase. RESULTS: Insulin was found to be higher in the study group (78.1 +/- 32.9 pmol/1 vs 63.0 +/- 27.6 pmol/1) although the differences were not significant. The insulin/glucose ratio was significantly higher in the study group (18.1 +/- 8.0 vs 13.9 +/- 7.7; p less than 0.05). Basal insulin and the insulin/glucose ratio were comparable among the obese and non obese patients of both groups. The remaining parameters studied dit not present any significant differences. No significant associations were observed between the values of insulin and insulin/glucose with the androgenic hormonal parameters. CONCLUSIONS: No elevated androgenic profile was observed in the women with previous gestational diabetes. The use of insulin and insulin/glucose values as indicators of insulin resistance did not demonstrate any correlation with the androgenic parameters.

Management of obstetric perineal tears: do obstetrics and gynaecology residents receive adequate training? Results of an anonymous survey.

Background/Aim. To evaluate the obstetrics and gynaecology residents' perspective of their training and experience in the management of perineal tears that occur during assisted vaginal delivery. We hypothesised that residents would perceive room for improvement in their knowledge of pelvic floor anatomy and the training received in tears repair. Design. Descriptive cross-sectional study. Population/Setting. Seventy-two major residents from all teaching hospitals in Catalonia. Methods. A questionnaire was designed to evaluate experience, perception of the training and supervision provided. Results. The questionnaire was sent to all residents (n = 72), receiving 46 responses (64%). The participants represented 15 out of the 16 teaching hospitals included in the study (94% of the hospitals represented). Approximately, 52% of residents were in their third year while 48% were in their fourth. The majority of them thought that their knowledge of pelvic floor anatomy was poor (62%), although 98% felt confident that they would know when an episiotomy was correctly indicated. The survey found that they lacked experience in the repair of major degree tears (70% had repaired fewer than ten), and most did not carry out followup procedures. Conclusion. The majority of them indicated that more training in this specific area is necessary (98%).

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.