Regular Menses Research Articles

Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness

To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness. Nonrandomized prospective clinical trial. We enrolled HIV-infected women aged 18-35 years in South Africa and Uganda who had regular menses, were sexually active, and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks. The median age of participants was 29 and their median CD4 cell count was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%) in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168 (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85-2.18). Pregnancy rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence, condom use, vaginal bleeding, and adverse events were similar. Five serious adverse events were reported, all in the non-ART group. ART use did not affect risk of ovulation or pregnancy in women taking COCs, suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.

Symptomatic Esophageal Granular Cell Tumor in a Young Female

Introduction: Granular cell tumors (GCTs) are rare forms of submucosal tumors that are infrequently found in the gastrointestinal tract (10% cases). However, in the gastrointestinal tract, the esophagus is the most commonly involved site (65% cases). Most GCTs are benign, asymptomatic, and less than 5 mm in size. Larger lesions are more likely symptomatic and have a higher malignant potential. We present the case of a young female with unresolving epigastric symptoms and weight loss caused by esophageal GCT which was diagnosed on endoscopic biopsy. Case Description: A 28-year-old, Caucasian, non-smoking female with no significant medical or family history was referred due to epigastric discomfort for 6 months. This was associated with a burning sensation and 15 pounds weight loss. She denied dysphagia, nausea, vomiting, blood in the stool, changes in her appetite or bowel habit. She had regular menses. Prior to presentation the patient was empirically treated with maximal doses of proton pump inhibitors, H 2 blockers and for Helicobacter pylori with no relief of symptoms. At current presentation, physical exam was unremarkable. All laboratory results including blood counts, amylase, lipase, and routine chemistries were within normal limits. In view of her history of significant weight loss and unresolving symptoms, endoscopy was performed. This revealed a 5 mm, whitish, submucosal nodule in the distal esophagus with positive biomarker staining (Figure 1a and 1b) suggestive of GCT. Subsequently, she underwent endoscopic mucosal resection of the lesion that resulted in complete resolution of symptoms.FigureDiscussion: GCTs are more frequent in males with a mean age at diagnosis of 45 years. They are often benign, asymptomatic, and usually less than 5 mm in size. They are most commonly found incidentally on endoscopy with an estimated incidence of 0.033%, representing about 1% of benign esophageal tumors. Although considered to be benign, GCTs have a malignant potential. The symptoms, if any, are often mild and include dysphagia, nausea, and burning sensation. Endoscopic mucosal resection is the recommended treatment especially if the lesions are >1 cm. There has been no described recurrence and prognosis is excellent. Although rare, it is important to consider GCT as a differential, especially in young patients presenting with mild, non-specific symptoms.

The Impact of Depot GnRH Agonist on AMH Levels in Healthy Reproductive-Aged Women

GnRH agonists (GnRHa) are being used experimentally in an attempt to preserve fertility in young female cancer patients undergoing chemotherapy. Anti-Müllerian hormone (AMH) produced by ovarian granulosa cells may serve as a marker of ovarian reserve, but it is not clear whether this marker is useful during GnRHa treatment. The purpose of this study was to determine the effect of a depot GnRHa on AMH levels. Depot leuprolide (3.75 mg) was administered in the midluteal phase (MLP) in healthy women. Assessments of AMH, FSH, LH, estradiol, and progesterone were performed in the early follicular phase (EFP) and MLP before GnRHa treatment and approximately 7, 14, and 30 days after GnRHa administration. The study was conducted in a university research center. Participants were 33 healthy, premenopausal women aged 18 to 45 years old with regular menses. EFP and MLP AMH levels were similar before GnRHa administration. Relative to MLP AMH levels, AMH decreased 7 days after GnRHa administration by a median of 24% (P < .001) and then increased above pretreatment levels 14 and 30 days after GnRHa by 13% and 32%, respectively (P < .001). Changes in AMH levels did not correlate with changes in gonadotropins, estradiol, or progesterone. Significant changes in AMH levels occur in the first 4 weeks after depot leuprolide administration, suggesting that AMH may not be a reliable marker of ovarian reserve during this interval. Changes in AMH occurred independent of gonadotropin levels, supporting a direct effect of GnRHa on granulosa cell expression of AMH or an indirect effect of GnRHa on the development and/or dynamics of the follicle pool.

Amenorrhea in eating disorders: poor stability of symptom after a one-year treatment.

To examine whether patients with Eating Disorders (ED) who restore menses differ from those who remain amenorrheic after treatment and to provide longitudinal data about this debated criterion of Anorexia Nervosa (AN). 184 outpatients were recruited: 50 patients with AN Restrictive type, 75 amenorrheic Eating Disorder Not Otherwise Specified (EDNOS) patients, 24 patients who recovered from AN with persistent amenorrhea, and 35 amenorrheic patients without ED. All participants were clinically assessed by psychiatrists and gynaecologists at the beginning of treatment and at the one-year follow-up. They also completed several psychometric tests: Eating Disorder Inventory-2, Temperament and Character Inventory, and Beck Depression Inventory. After treatment, a large portion of the sample resumed menses but very few recovered completely from the ED. No psychopathological variables could clearly predict the recovery of menses in the different groups. However, Body Mass Index and some biological variables were associated with restoration of menses in ED patients. Resumption of menses was not associated with a less severe eating symptomatology at the beginning of treatment nor with unequivocal psychopathological changes after treatment. It is important that clinicians consider not only the presence or absence of regular menses but also that they improve both ED screening and assessment in amenorrheic patients. Amenorrhea does not seem to represent a specific predictor of severity of illness or to show prognostic value.

The clinical significance of small endometrial polyps

ObjectiveSmall endometrial polyps are relatively common in asymptomatic women and may regress spontaneously. In symptomatic women, the finding of a small polyp (<1cm diameter) raises the question of the clinical pertinence and necessity of excision. Sparse data are available on the effectiveness of hysteroscopic excision of small polyps to manage abnormal uterine bleeding. The aim of this study was to assess outcome after hysteroscopic excision of small endometrial polyps in symptomatic patients. Study designThis was an observational cohort study enrolling 255 premenopausal women presenting with abnormal uterine bleeding and a small endometrial polyp on office hysteroscopy, undertaken between January 2004 and February 2007. The study group was referred for polypectomy by operative hysteroscopy. The outcome of the procedure was reviewed 6–12 months later by a telephone interview to assess the pattern of uterine bleeding after the procedure and overall satisfaction. ResultsSignificant improvement in the magnitude of bleeding was experienced by 70% of participants, but only 30% of them reported return to regular menses. Satisfaction with the procedure was reported by 80%. Younger patients reported a less favorable bleeding pattern and were found to be less satisfied with the outcome of the procedure. ConclusionsSymptomatic women with small endometrial polyps can be treated safely and efficiently with hysteroscopic excision. In the younger age group of patients, however, the outcome of the procedure may be less favorable and may necessitate the addition of endometrial ablation to improve outcome and increase patient satisfaction.

Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study

BackgroundRegistry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis (RENEW) was a 5-year, phase IV study in which the safety of Mitoxantrone was monitored in a patient cohort from the United States (US). The objective of the study was to evaluate the long-term safety profile of Mitoxantrone in patients with secondary progressive multiple sclerosis (SPMS), progressive relapsing multiple sclerosis (PRMS), and worsening relapsing-remitting multiple sclerosis (RRMS).MethodsOverall, 509 patients (395 SPMS, 81 worsening RRMS, 33 PRMS) were enrolled and treated at 46 multiple sclerosis (MS) treatment centers located in the US. Patients received Mitoxantrone in accordance with the package insert every 3 months. During the treatment phase, patients received laboratory workups and cardiac monitoring every 3 months and then annually for a total of 5 years.ResultsFive hundred and nine subjects were enrolled in this trial and received at least one infusion of Mitoxantrone. Overall, 172 (33.8%) completed the 5-year trial (i.e., participated for 5 years ± 3 months [treatment + follow-up]); 337 (66.2%) did not complete the 5-year trial. Annual follow-up data were available for 250 of 509 enrolled patients. Left ventricular ejection fraction reduction under 50% was reported in 27 (5.3%) patients during the treatment phase (n = 509) and 14 (5.6%) patients during the annual follow-up phase (n = 250). Signs and symptoms of congestive heart failure were observed in 10 (2.0%) patients (six during treatment phase and four during the annual follow-up phase). Post-hoc analyses of the risk for cardiotoxicity outcomes revealed that cumulative dose exposure is the primary risk factor associated with the risk of cardiac toxicity with Mitoxantrone. Therapy-related leukemia was reported in three (0.6%) patients who received total cumulative Mitoxantrone doses of 73.5 mg/m2, 107.3 mg/m2, and 97.1 mg/m2 respectively. During the treatment phase, persistent amenorrhea developed in 22% (28/128) of women with regular menses and 51% (25/49) of women with irregular menses at baseline. During the annual follow-up phase, persistent amenorrhea developed in 5% (4/73) of women with regular menses at baseline.ConclusionRENEW results are consistent with the known safety profile of Mitoxantrone, and provide additional long-term safety data for Mitoxantrone in MS patients.

In PCOS patients the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone

Background & aimsPolycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and hyperandrogenism and by insulin resistance and related metabolic alterations. Both metformin and anti-androgens, such as spironolactone, are used to ameliorate the different aspects of this disorder. We investigated whether therapy with metformin plus low-dose spironolactone is more effective than metformin alone in PCOS patients. Methods and resultsFifty-six PCOS patients were randomized in two groups: group A (28 patients) was treated with metformin (1700 mg/die) and group B (28 patients) was treated with metformin (1700 mg/die) plus low-dose spironolactone (25 mg/die). Anthropometric, hormonal and metabolic parameters were evaluated at baseline and after six months of treatment. After therapy regular menses were restored in approximately 82% of group A patients (P < 0.001) and in 68% of group B patients (P < 0.001). Circulating testosterone, Δ-4-androstenedione and Hirsutism Score (HS) significantly decreased in both groups. However, dehydro-epiandrosterone sulphate significantly decreased only in group B, and HS underwent a stronger reduction in group B (P < 0.001). At baseline, 39/56 (69.6%) patients met the diagnostic criteria for metabolic syndrome, but only one patient met these criteria after treatment. ConclusionsThis study confirms the beneficial effects of metformin in PCOS patients. It also indicates that the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism as compared to metformin alone. Clinicaltrial.gov numberNCT01526616.

Tamoxifen and ovarian function.

BackgroundSome studies suggest that the clinical parameter “amenorrhea” is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy.Materials and MethodsBetween 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011.ResultsThree patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values.ConclusionsAmenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy.

ERβ-dependent effects on uterine endothelial cells are cell specific and mediated via Sp1

STUDY QUESTIONWhat are the in vitro effects of estrogen receptor β (ERβ) activation on the function of endothelial cells (ECs) from different vascular beds: human endometrial ECs (HEECs; endometrium), uterine myometrial microvascular ECs (UtMVECs; myometrium) and human umbilical vein ECs (HUVECs)?SUMMARY ANSWERStudies conducted in vitro demonstrate that the ERβ agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) has EC type-specific effects on patterns of gene expression and network formation. Identification of a key role for the transcription factor Sp1 in ERβ-dependent signaling in uterine ECs offers new insights into cell-specific molecular mechanisms of estrogen action in the human uterus.WHAT IS KNOWN ALREADYEstrogens, acting via ERs (ERα and ERβ), have important, body-wide impacts on the vasculature. The human uterus is an estrogen target organ, the endometrial lining of which exhibits physiological, cyclical angiogenesis. In fixed tissue sections, human endometrial ECs are immunopositive for ERβ.STUDY DESIGN, SIZE, DURATIONCells were treated with a vehicle control or the ERβ agonist, DPN, for 2 h or 24 h (n = 5) followed by gene expression analysis. Functional assays were analyzed after a 16 h incubation with ligand (n = 5).PARTICIPANT/MATERIALS, SETTING, METHODSAnalysis of DPN-treated ECs using Taqman gene array cards focused on genes involved in angiogenesis and inflammation identified cell type-specific ERβ-dependent changes in gene expression, with validation using qPCR and immunohistochemistry. Molecular mechanisms involved in ERβ signaling were investigated using bioinformatics, reporter assays, immunoprecipitation, siRNA and a specific inhibitor blocking Sp1-binding sites. The endometrium and myometrium from women with regular menses were used to validate the protein expression of candidate genes.MAIN RESULTS AND THE ROLE OF CHANCEHEECs and UtMVECs were ERβ+/ERα−. Treatment of ECs with DPN had opposite effects on network formation: a decrease in network formation in HEECs (P ≤ 0.001) but an increase in UtMVECs (P ≤ 0.05). Genomic analysis identified opposite changes in ERβ target gene expression with only three common transcripts (HEY1, ICAM1, CASP1) in all three ECs; a unique profile was observed for each. An important role for Sp1 was identified, consistent with the regulation of ERβ target genes via association with the transcription factor (‘tethered’ mechanism).LIMITATIONS, REASONS FOR CAUTIONThe study was mainly carried out in vitro using ECs of which one type was immortalized. Although the analysis of the protein expression of candidate genes was carried out using intact tissue samples from patients, investigations into in vivo angiogenesis were not carried out.WIDER IMPLICATIONS OF THE FINDINGSThese results have implications for our understanding of the mechanisms responsible for ERβ-dependent changes in EC gene expression in hormone-dependent disorders.STUDY FUNDING/COMPETEING INTEREST(S)The study was funded by a Medical Research Council Programme Grant. E.G. is the recipient of an MRC Career Development Fellowship. The authors have nothing to disclose.

Analysis of Tubal Patency After Essure Placement

Study ObjectiveTo evaluate tubal patency after hysteroscopic sterilization using the Essure microinsert (Conceptus Inc, San Carlos, CA). DesignA retrospective longitudinal cohort study. Design ClassificationII-3. SettingPatients undergoing hysteroscopic sterilization in the outpatient clinic of a university-based hospital in Southeast Texas from July 2009 to November 2011. PatientsTwo hundred twenty-nine women (ages 21–44 yrs, 71% Hispanic) desiring sterilization with a history of regular menses, demonstrated prior fertility (≥1 live birth), and the ability to use an alternative contraceptive method for at least 90 days after coil placement were included. Twenty six patients in this cohort were excluded because of failure to perform a hysterosalpingogram (HSG), tubal perforation, severe dyspareunia, a history of ectopic pregnancy, tubal surgery, or cervical intraepithelial neoplasia. InterventionsNot applicable. Measurements and Main ResultsHSGs were assessed for microinsert location and tubal occlusion. Two hundred three patients were included for analysis. After the successful bilateral hysteroscopic placement of Essure microinserts in fallopian tubes, all patients returned for the first follow-up HSG a mean of 103 ± 38 days after the procedure. Patients with fallopian tube patency at the initial HSG returned for second and/or third HSGs as needed at 192 ± 45 and 291 ± 97 days, respectively. Correct device placement was confirmed in 100% of cases at the first HSG. The tubal patency rates at the 90-day and 180-day HSGs were 16.1% (95% confidence interval, 7.4%–31.7%) and 5.8% (95% CI, 1.2%–24.4%), respectively. These rates were estimated by the accelerated failure time model with log normal distribution and interval censored time to event. The 16.1% 90-day tubal patency rate is significantly different from the 8% rate reported by Cooper et al in the 2003 multicenter phase III pivotal trial (p <.001). ConclusionOur data indicate that hysteroscopic sterilization with Essure results in a higher initial tubal patency rate than previously reported. Multivariate analyses are needed to identify factors associated with an increased risk of postprocedure tubal patency.

Fertility rate and subsequent pregnancy outcomes after conservative surgical techniques in postpartum hemorrhage: 15 years of literature

To investigate the most appropriate surgical technique for optimizing hemostasis and preservation of subsequent fertility after postpartum hemorrhage (PPH). Systematic review of the literature. Not applicable. None. Review of MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library. Comparison of the effectiveness of conservative surgical techniques, separately or together, with respect to success rate (ability to stop bleeding and preserve the uterus), fertility rate (subsequent pregnancies or the return of regular menstrual cycles), complication rate of the procedure, and the outcomes of subsequent pregnancies in terms of type of delivery and eventual delivery complications. Compressive sutures and vessel embolization may be considered life-saving procedures by achieving the best hemostatic efficacy. Data on restoration of menses and pregnancy rates after these procedures are limited by short-term follow-up and by the paucity of studies, especially for vascular ligation. Pelvic vessel embolization and compressive sutures are associated with high rates of restoration of regular menses and successive pregnancies, even if the former is burdened by an increased rate of placental disorders and fetal growth restriction and the latter by an increased risk of cesarean deliveries and PPH recurrence. Randomized trials would be desirable to define the best management of PPH.

Regular menses at 73? A peculiar presentation of postmenopausal bleeding

Post menopausal bleeding is one of the most common conditions referred to gynaecology departments. Up to 5% of these women are found to have malignant, or pre-malignant lesions, with early detection and investigation being crucial for curative treatment. We report on the case of a 73-year-old women referred for having regular menses since 14 years of age and discuss the current investigation and management of post menopausal bleeding.

Reversal and Relapse of Hypogonadotropic Hypogonadism: Resilience and Fragility of the Reproductive Neuroendocrine System

A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial pubertal development in patients with reversal vs IHH patients without reversal. Fifteen patients with reversal (30%) had Kallmann syndrome (IHH and anosmia); one had undetectable olfactory bulbs on a brain magnetic resonance imaging scan. Subjects with reversal were enriched for mutations affecting neurokinin B signaling compared with a cohort of IHH patients without reversal (10% vs 3%, P = .044), had comparable frequencies of mutations in FGFR1, PROKR2, and GNRHR, and had no mutations in KAL1. Five men did not sustain their reversal and again developed hypogonadotropism. Reversal of IHH may be more widespread than previously appreciated and occurs across a broad range of genotypes and phenotypes. Enrichment for mutations that disrupt neurokinin B signaling in patients who reversed indicates that, despite the importance of this signaling pathway for normal pubertal timing, its function is dispensable later in life. The occurrence of reversal in a patient with no olfactory bulbs demonstrates that these structures are not essential for normal reproductive function. Patients with IHH require lifelong monitoring for reversal and, if reversal occurs, subsequent relapse also may occur.

Age at menarche and prevalence of menstrual abnormalities among adolescents in Zaria, northern Nigeria

Background: Nigerian adolescents constitute about 20% of the total population. Problems associated with menstruation affect 75% of adolescent females in both the developing and the developed world. Objectives: The objective of this study is to establish the age at menarche and menstrual abnormalities among adolescents in secondary schools in Zaria. Materials and Methods: A descriptive cross sectional study in which a self-administered pretested, semi-structured questionnaire in english was administered to 535 female secondary school students in Zaria, northern Nigeria. The students were selected from five schools that were chosen by simple random sampling from a list of schools in Zaria metropolis. Information obtained included age at menarche and menstruation related issues. Results: Of the 535 female secondary school students interviewed, 448 (83.7%) were in senior secondary school. The mean age of the respondents was 15.35 ± 1.48 years. The average age at menarche was 12.53 ± 1.33 years. Most respondents, 369 (69.0%) experienced regular menses. The average duration of menstruation was 5.45 ± 1.81 days in 354 (66.2%) of the respondents. Three hundred and forty-four (64.3%) of the respondents had dysmenorrhea, and it was severe in 229 (66.6%) of them. Only, 137 (25.6%) experienced premenstrual symptoms, the most common symptom being breast tenderness in 62 respondents (45.2%). Conclusion: The age at menarche and the menstrual pattern amongst adolescents in Zaria, northern Nigeria is similar to findings from other parts of Nigeria as well as from other parts of the world. Further studies are however needed to explore the full range of menstrual abnormalities that can occur in the adolescent age group.

Postpartum panhypopituitarism with spontaneous pregnancy

We are reporting a case of a patient found to be pregnant in the setting of panhypopituitarism. There are an only few reports of spontaneous pregnancy in patients with panhypopituitarism. This is a 26-year-old female who was admitted due to symptomatic hypoglycemia. Past medical history is significant for uncomplicated pregnancy with C-section delivery 1 year before admission. She was not able to breastfeed the baby in postpartum period. Her menses have been irregular since then. She also noticed increasing fatigue, muscle weakness, episodic diarrhea and 70 pounds weight loss. Physical exam was remarkable for hypotension. Work up showed elevated levels of beta-HCG, hyponatremia, normal anion gap metabolic acidosis, normochromic anemia, and low cortisol levels, appropriate low levels of insulin and C-peptide. Hypoglycemia panel revealed undetectable levels of sulphonylureas. Serum levels for pituitary hormones showed low levels of ACTH, prolactin and IGF-1, normal levels of FSH, and inappropriate normal levels of TSH in the setting of decreased T4. Stress doses of hydrocortisone were initiated along with thyroid hormone replacement. Brain MRI was found to be unremarkable. Sheehan’s syndrome is a very rare complication of pregnancy when necrosis of the pituitary gland occurs after severe hemorrhage and hypotension upon delivery. Small sella size, disseminated intravascular coagulopathy, stress of the delivery and autoimmunity are also implicated as possible causes of Sheehan’s syndrome. We should be very attentive for symptoms as failure to lactate and failure to resume regular menses after delivery as they can be the first manifestation of the disease. Infertility is common in these patients, but in very few of them gonadotropin response will be present due to residual pituitary function and spontaneous pregnancy can occur. Proper management of these patients during pregnancy will also be very important since a high risk of miscarriages can be expected.

Twice-Daily Application of HIV Microbicides Alters the Vaginal Microbiota

ABSTRACTVaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based “universal” placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates.

Prevalence of macroprolactinaemia in regularly menstruating women with non-toxic goitre or autoimmune thyroid disease

BackgroundThe so called “big-big” prolactin (Prl), also known as macroprolactin is formed by Prl-immunoglobulin (Prl-IgG) complexes and may cause elevation of serum Prl concentrations measured by standard assays, potentially leading to unnecessary investigations and/or treatment. In our study, we have endeavoured to assess the prevalence of macroprolactinaemia in euthyroid, regularly menstruating women with thyroid disease, as well as to assess whether autoimmune thyroid disease may result in an increased prevalence of macroprolactinaemia.Material and methodsWe measured serum Prl in 182 regularly menstruating women aged 32.7 ± 7.5 years (mean ± SD, range 17–46 years) who attended endocrine clinic either for investigation of non-toxic goitre (n = 86, age 33.2 ± 7.8 years) or with autoimmune thyroid disease (n = 96, age 32.3 ± 7.2 years). Autoimmune thyroid disease was defined as raised titre of at least one anti-thyroid antibody [anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg) and/or anti-TSH-receptor (anti-TSH-R) antibodies]. All women were clinically and biochemically euthyroid, either without or on treatment with L-thyroxine. In those with raised Prl (i.e., above 530 mIU/l) we ruled out the presence of macroprolactinaemia by polyethylene glycol (PEG) precipitation method.ResultsThere was no significant age difference between women with and without autoimmune thyroid disease (p = 0.84). Raised Prl concentrations were found in 10 women with thyroid disease (5.5%), and of those a significant macroprolactinaemia (i.e., reduction of Prl concentrations of more than 60% after PEG precipitation) was found in 9 subjects (4.94%). There were no differences in the prevalence of macroprolactinaemia between women with autoimmune thyroid disease (4 out of 96), and without autoimmune thyroid disease (5 out of 86, p = 0.75).ConclusionsApproximately one out of twenty women with regular menses is likely to have raised serum Prl that is usually caused by the presence of macroprolactinaemia. Though structure of macroprolactin involves Prl-IgG complexes, there is no evidence that autoimmune thyroid disease is associated with raised prevalence of macroprolactinaemia.

A mullerian anomaly ‘‘without classification’’: Septate uterus with double cervix and longitudinal vaginal septum

The incidence of congenital uterine anomalies in the general population is estimated to be 0.001e10% [1]. The most commonly seen anomalies are septate and arcuate uteri, which represent 75% of all mullerian anomalies. The majority of mullerian duct anomalies are considered to be sporadic or multifactorial in nature; however, polygenic and genetic patterns of inheritance have been described [2,3]. There are two theories to explain the development of mullerian duct anomalies, the classical unidirectional regression theory, and an alternative bidirectional theory in which it is hypothesized that the process proceeds simultaneously in both the cranial and the caudal directions. Anomalies such as a complete septum with a duplicated cervix or an isolated vertical upper vaginal septum could only be explained by the second theory [4,5]. We report the case of a woman with a complete uterine septum, and a double cervix with a longitudinal vaginal septum, and search the available literature for similar cases. A 28-year-old nulligravida woman was admitted to our hospital due to being unable to conceive. She had been married for 2 years and had never used any contraceptive methods. She had regular menses but had dysmenorrhea and sometimes also dyspareunia. A longitudinal vaginal septum from the midportion of the vagina to the cervix, and the presence of two separate cervixes were identified following a speculum examination. Transvaginal ultrasound showed a normal uterine contour, then hysterosalpingography was performed. When a contrast media was injected into the right cervix, the uterine cavity was filled, however, the fallopian tubes were not. When the contrast media was then injected into the left cervix and uterine cavity, the left fallopian tube and pelvic cavity filled with contrast media, but the right fallopian tube was not filled with contrast media. Following

Hormônio anti-Mülleriano sérico para predição da resposta ovariana em ciclos de reprodução assistida

To compare serum anti-Mullerian hormone (AMH) levels on the seventh day of ovarian stimulation between normal and poor responders. Nineteen women aged ≥35, presenting with regular menses, submitted to ovarian stimulation for assisted reproduction were included. Women with endometriosis, polycystic ovarian syndrome or those who were previously submitted to ovarian surgery were excluded. On the basal and seventh day of ovarian stimulation, a peripheral blood sample was drawn for the determination of AMH, FSH and estradiol levels. AMH levels were assessed by ELISA and FSH, and estradiol by immunochemiluminescence. At the end of the stimulation cycle patients were classified as normal responders (if four or more oocytes were obtained during oocyte retrieval) or poor responders (if less than four oocytes were obtained during oocyte retrieval or if the cycle was cancelled due to failure of ovulation induction) and comparatively analyzed by the t-test for hormonal levels, length of ovarian stimulation, number of follicles retrieved, and number of produced and transferred embryos. The association between AMH and these parameters was also analyzed by the Spearman correlation test. There was no significant difference between groups for basal or the seventh day as to AMH, FSH and estradiol levels. There was a significant correlation between seventh day AMH levels and the total amount of exogenous FSH used (p=0.02). AMH levels on the seventh day of the ovarian stimulation cycle do not seem to predict the pattern of ovarian response and their determination is not recommended for this purpose.

Investigation of oxidative balance in patients with dysmenorrhea by multiple serum markers

To investigate the level of oxidative stress in patients with dysmenorrhea by multiple serum markers including malondialdehyde (MDA), nitrotyrosine (3-NT), deoxyguanosine (8-OHdG) and superoxide dismutase (SOD). Fifty-eight women, aged between 20 and 34, who had had regular menses for at least six previous cycles, were involved. The women were divided into two groups. The study group consisted of 33 patients with primary dysmenorrhea, and the control group consisted of 25 healthy women. Demographic characteristics of patients were similar between the two groups. The serum MDA levels were 1.32±0.46 and 0.91±0.26 nmol/mL for the dysmenorrhea and control groups, respectively (p<0.001). The differences in plasma levels of 3-NT, SOD and serum 8-OhdG were similar in both groups (p>0.05). Also, no correlation was found between the severity of dysmenorrhea and the levels of oxidative markers. Oxidative stress is slightly aggravated in patients with dysmenorrhea.