Women In Reproductive Years Research Articles

Importance of engaging obstetrician/gynecologists in cardiovascular disease prevention

To review recent evidence regarding traditional and sex-specific factors identified among women during their reproductive years and their importance in lifetime risk for cardiovascular disease (CVD). Longitudinal studies demonstrated a woman's burden of risk during her reproductive years is associated with future risk of CVD. Similarly, women with a healthy lifestyle are relatively protected and have the lowest lifetime risk. Some primary prevention strategies, when implemented during this age window, were cost-effective. The link between pregnancy outcome and future CVD risk is now better understood, and evidence now relates pregnancy-associated hypertension and diabetes, as well as a preterm delivery or a low birth weight delivery, to excess risk. Gaps in preventive healthcare for women in this age group included low rates of treatment initiation for hypertension and failure to follow guidelines for diabetes surveillance among women with a history of gestational diabetes. Knowledge gaps for standard CVD prevention, as well as the link between pregnancy complications and future CVD risk, were identified among both primary care providers and obstetrician/gynecologists. Traditional and sex-specific risk factors for CVD present during women's reproductive years. Engaging the obstetrician/gynecologist provides a strategy to enhance prevention.

Pregnancy after bariatric surgery – a review of benefits and risks

When other weight loss attempts have failed, bariatric surgery offers a successful alternative for obesity. Since operations are performed during women's reproductive years, the number of pregnant women with prior bariatric surgery is increasing. Bariatric surgery results in restriction of food intake and/or malabsorption leading to weight loss, but may induce a risk for malnutrition and pregnancy complications. Systematically conducted review addressing pregnancy after bariatric surgery using the PubMed and Cochrane databases. Birthweight, gestational age, birth defects, preeclampsia, gestational diabetes mellitus, and mode of delivery. We included 17 articles in English, comparing pregnancies in women with prior bariatric surgery to pregnancies in a control group without this. There was considerable heterogeneity in study design and six of the studies included <50 women with bariatric surgery. Eight studies described lower birthweight and lower risk of macrosomia after bariatric surgery, but in six there was no difference. Five studies indicated a higher risk of small-for-gestational age infants, but only compared with non-obese women or severely obese controls. There was no difference in gestational length. Only one study suggested a higher risk of birth defects after surgery. The maternal risk of preeclampsia and gestational diabetes mellitus was lower after bariatric surgery. Results regarding mode of delivery are conflicting. Pregnancy after bariatric surgery seems safe but larger studies matching or adjusting for body mass index are needed to improve the surveillance of these pregnancies and to assist in preventing adverse outcomes.

Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding

Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea. The primary objective of this review was to investigate the effectiveness of NSAIDs in achieving a reduction in menstrual blood loss in women of reproductive years with HMB. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL in July 2012 and reference lists of articles. We also contacted manufacturers and researchers in the field. The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their heavy menstrual blood loss. Eighteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data and one trial with missing variances were described in data tables. As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than either tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system (Progestasert), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. NSAIDs reduce HMB when compared with placebo but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of intrauterine system, Progestasert.

Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause

Hyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships. Blood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI). PCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS. Early postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.

Tuberculosis in Pregnant and Postpartum Women: Epidemiology, Management, and Research Gaps

Tuberculosis is most common during a woman's reproductive years and is a major cause of maternal-child mortality. National guidelines for screening and management vary widely owing to insufficient data. In this article, we review the available data on (1) the global burden of tuberculosis in women of reproductive age; (2) how pregnancy and the postpartum period affect the course of tuberculosis; (3) how to screen and diagnose pregnant and postpartum women for active and latent tuberculosis; (4) the management of active and latent tuberculosis in pregnancy and the postpartum period, including the safety of tuberculosis medications; and (5) infant outcomes. We also include data on HIV/tuberculosis coinfection and drug-resistant tuberculosis. Finally, we highlight research gaps in tuberculosis in pregnant and postpartum women.

Endometrial regeneration and endometrial stem/progenitor cells

The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed.

The Effects of Infant Feeding Practices on Infant and Maternal Health in a Medieval Community

Breastfeeding practices exert profound effects on infant and maternal health. This paper explores this for a Medieval English population using a synthesis of skeletal data from the archaeological site at Wharram Percy, England. Duration of breastfeeding was assessed using δ15N levels in infant bones. Infant health was evaluated using bone growth. The aspect of female health investigated was bone mineral density (BMD). Results indicate that duration of weaning was normally about eighteen months. Prior to about eighteen months of age infant skeletal growth matched that of a recent reference population. After this it began to fall behind. Women in the 30–49 year age group showed depressed BMD compared with younger women, suggesting significant pre-menopausal loss of BMD. The growth data suggest that the beneficial effects of breast milk permitted rapid growth of infants, but once breastfeeding ceased, growth faltered. In modern populations, maternal BMD normally diminishes during lactation, but subsequently recovers. At Wharram Percy, the depressed BMD in the women's later reproductive years suggest that lactational losses may not have been recovered. Extended lactation under conditions of poor nutrition and a physically demanding lifestyle may have played a part in this. In addition to pre-menopausal BMD loss, the Wharram Percy women showed normal post-menopausal loss. The combined effect was skeletal fragility in old age, and consequent osteoporotic fractures.

An Economic Model of Amniocentesis Choice

Medical practitioners typically utilize the following protocol when advising pregnant women about testing for the possibility of genetic disorders: Pregnant women over the age of 35 should be tested for Down syndrome and other genetic disorders; for younger women, such tests are discouraged since they can cause a miscarriage. The logic appears compelling. The rate at which amniocentesis causes a miscarriage is constant while genetic disorders rise over a woman's reproductive years. Hence the potential benefit from testing - being able to terminate a fetus with a genetic disorder - rises with maternal age. We argue that this logic is incomplete. While the benefits to testing rise with age, so do the costs. While undergoing an amniocentesis always entails the risk of miscarriage of a healthy fetus, these costs are lower at early ages, because there is a higher probability of being able to replace a miscarried fetus with a healthy birth at a later age. We develop and calibrate a dynamic model of amniocentesis choice to explore this tradeoff. For parameters that characterize realistic age patterns of chromosomal abnormalities, fertility rates and miscarriages following amniocentesis, our model implies a falling, rather than rising, rate of amniocentesis as women approach menopause.

RAPID REPORT: Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats

Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected.

An economic model of amniocentesis choice

Medical practitioners typically utilize the following protocol when advising pregnant women about testing for the possibility of genetic disorders with their fetus: Pregnant women over the age of 35 should be tested for Down syndrome and other genetic disorders, while for younger women, such tests are discouraged (or not discussed) as the test can cause a pregnancy to miscarry. The logic appears compelling. The rate at which amniocentesis causes a pregnancy to miscarry is constant while the rate of genetic disorder rises substantially over a woman's reproductive years. Hence the potential benefit from testing - being able to terminate a fetus that is known to have a genetic disorder - rises with maternal age. This article argues that this logic is incomplete. While the benefits to testing do rise with age, the costs rise as well. Undergoing an amniocentesis always entails the risk of inducing a miscarriage of a healthy fetus. However, these costs are lower at early ages, because there is a higher probability of being able to replace a miscarried fetus with a healthy birth at a later age. We develop and calibrate a dynamic model of amniocentesis choice to explore this tradeoff. For parameters that characterize realistic age patterns of chromosomal abnormalities, fertility rates and miscarriages following amniocentesis, our model implies a falling, rather than rising, rate of amniocentesis as women approach menopause.

Aging, estrogens, and episodic memory in women.

To review the relation in midlife and beyond between estrogen exposures and episodic memory in women. Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years. Focused literature review, including a summary of a systematic search of clinical trials of estrogens in which outcomes included an objective measure of episodic memory. The natural menopause transition is not associated with the objective changes in episodic memory. Strong clinical trial evidence indicates that initiating estrogen-containing hormone therapy after the age of about 60 years does not benefit episodic memory. Clinical trial findings in middle-aged women before the age of 60 years are limited by smaller sample sizes and shorter treatment durations, but these also do not indicate substantial memory effects. Limited short-term evidence, however, suggests that estrogens may improve verbal memory after surgical menopause. Although hormone therapy initiation in old age increases dementia risk, observational studies raise the question of an early critical window during which midlife estrogen therapy reduces late-life Alzheimer disease. However, almost no data address whether midlife estrogen therapy affects episodic memory in old age. Episodic memory is not substantially impacted by the natural menopause transition or improved by the use of estrogen-containing hormone therapy after the age of 60 years. Further research is needed to determine whether outcomes differ after surgical menopause or whether episodic memory later in life is modified by midlife estrogenic exposures.

Postpartum Outcome of Cervical Intraepithelial Neoplasia in Pregnant Women Determined by Route of Delivery

Cervical intraepithelial neoplasia (CIN) has its highest incidence during women's reproductive years. During 2 sequential 7-year periods, 1994 to 2000 and 2001 to 2007, 3695 and 3894 deliveries were performed, respectively, at Osaka University Hospital. CIN was detected in 21 cases (0.57%) during 1994-2000 and in 43 cases (1.1%) during 2001-2007. By comparison, cervical intraepithelial neoplasia-complicated pregnancies increased significantly in the latter period (P = .015 by Fisher exact test, Odds ratio = 1.95; 95%CI: 1.16-3.30). We observed CIN regression in 34 (76%) of 45 cases of vaginal delivery and in 6 (50%) of 12 cases of cesarean delivery, indicating that the outcome of an initially diagnosed CIN and the delivery routes appeared not to be significantly related. However, a different result was obtained when only those patients whose CIN lesions persisted until the delivery were analyzed. Among the 35 such cases in the vaginal delivery group, 24 cases (69%) regressed after the delivery; in 8 such cases from the cesarean delivery group, only 2 cases (25%) regressed afterward. Our study clearly shows that pregnancy complicated with CIN is increasing rapidly in Japan. We also find that there is a significantly more frequent postpartum regression of biopsy-proven CIN lesions following a vaginal delivery compared to cesarean section (P = .042 by Fisher exact test, Odds ratio = 6.55; 95% CI: 1.13-37.8).

Oral contraceptive pill for heavy menstrual bleeding

Menorrhagia (heavy menstrual bleeding) is a benign yet debilitating social and health condition. Treatments prescribed in order to reduce excessive menstrual blood loss include prostaglandin synthetase inhibitors, antifibrinolytics, the oral contraceptive pill and other hormones. The combined oral contraceptive pill (OCP) is claimed to have a variety of beneficial, inducing a regular shedding of a thinner endometrium and inhibiting ovulation thus having the effect of treating menorrhagia and providing contraception. To determine the effectiveness of oral contraceptive pills compared with other medical therapies, placebo or no therapy in the treatment of heavy menstrual bleeding. We searched the Menstrual Disorders and Subfertility Group trials register (search dates: Oct 1996, May 2002, June 2004, April 2006 and June 2009) for all publications which describe randomised trials of OCP for the treatment of menorrhagia. This register is based on regular searches of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, the hand searching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. All randomised controlled comparisons of OCP versus other medical therapies, placebo or no treatment for the treatment of menorrhagia. Women of reproductive years with regular heavy periods, measured either objectively or subjectively and greater than, or equal to, two months follow up. All assessments of trial quality and data extraction were performed unblinded by at least two reviewers. Only one trial of 45 women met the inclusion criteria and none were excluded. As the trial used a cross-over design, only data from the first treatment period (cycles three and four) were analysed. The results from all the three mefenamic acid groups were combined. There was no significant difference in menstrual blood loss (MBL) between those women treated with the OCP and danazol, mefenamic acid or naproxen. One small study found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study is not sufficient to adequately assess the effectiveness of OCP.This review was unable to achieve its stated objectives because of the paucity of the data.

Contraception and pregnancy then and now: Examining the experiences of a cohort of mid‐age Australian women

More than 50% of women who have an unplanned pregnancy report using a contraceptive method. Since the launch of the pill 50 years ago, a number of cross-sectional surveys have examined contraceptive use in the Australian context. There is, however, little data on contraceptive use and efficacy over a woman's reproductive years. To determine the pattern of contraceptive use of Australian women over their reproductive lifespan, with particular emphasis on the relationship between contraceptive use and pregnancy. One thousand women from the mid-age cohort of the Australian Women's Longitudinal Study were invited to participate in the Family Planning survey by completing a questionnaire about their reproductive histories. Completed questionnaires were received for 812 women. The contraceptive pill was the most commonly ever used contraceptive method at 94% and also the most commonly used method prior to all pregnancies. Contraceptive failure increased with increasing gravidity; 11.4% with the first pregnancy to 23.0% with the fourth pregnancy, while 28.8% of the respondents reported an 'accidental' pregnancy due to stopping contraception for reasons such as concern about long-term effects and media stories. While surveys indicate that 66-70% of Australian women use a contraceptive method, more than half of unplanned pregnancies apparently occur in women using contraception. The modern Australian woman, in common with her predecessors, still faces significant challenges in her fertility management. This survey provides a longitudinal perspective on contraceptive use in relation to pregnancy and highlights the issue of efficacy of contraceptives in real-life situations.

Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium.

Human endometrium is a highly regenerative tissue undergoing more than 400 cycles of growth, differentiation, and shedding during a woman's reproductive years. Endometrial regeneration is likely mediated by adult stem/progenitor cells. This study investigated key stem cell properties of individual clonogenic epithelial and stromal cells obtained from human endometrium. Single-cell suspensions of endometrial epithelial or stromal cells were obtained from hysterectomy tissues from 15 women experiencing normal menstrual cycles, and were cultured at clonal density (10 cells/cm(2)) or limiting dilution. The adult stem cell properties-self-renewal, high proliferative potential, and differentiation of single epithelial and stromal cells-were assessed by harvesting individual colonies and undertaking serial clonal culture, serial passaging, and culture in differentiation-induction media, respectively. Lineage differentiation markers were examined by RT-PCR, immunocytochemistry, and flow cytometry. Rare single human endometrial EpCAM(+) epithelial cells and EpCAM(-) stromal cells demonstrated self-renewal by serially cloning >3 times and underwent >30 population doublings over 4 mo in culture. Clonally derived epithelial cells differentiated into cytokeratin(+) gland-like structures in three dimensional culture. Single stromal cells were multipotent, as their progeny differentiated into smooth muscle cells, adipocytes, chondrocytes, and osteoblasts. Stromal clones expressed mesenchymal stem cell (MSC) markers ITGB1 (CD29), CD44, NT5E (CD73), THY1 (CD90), ENG (CD105), PDGFRB (CD140B), MCAM (CD146) but not endothelial or hemopoietic markers PECAM1 (CD31), CD34, PTPRC (CD45). Adult human endometrium contains rare epithelial progenitors and MSCs, likely responsible for its immense regenerative capacity, which may also have critical roles in the development of endometriosis and endometrial cancer. Human endometrium may provide a readily available source of MSCs for cell-based therapies.

003. ENDOMETRIUM: CINDERELLA TISSUE IN A STEM CELL WORLD

Despite human endometrium undergoing more than 400 cycles of regeneration, differentiation and shedding during a woman's reproductive years, and that in non-menstruating species (eg rodents) there are cycles of endometrial growth and apoptosis, endometrial stem/progenitor cells have only recently been identified. Since there are no specific stem cell markers, initial studies using functional approaches identified candidate epithelial and stromal endometrial stem/progenitor cells as colony forming cells/units (CFU) (1). Further evaluation of key stem cell properties of individual CFU demonstrated that rare EpCAM+ epithelial cells and EpCAM- stromal cells underwent self renewal by serial subcloning &gt;3 times and underwent &gt;30 population doublings in culture. Clonally-derived epithelial cells differentiated into cytokeratin+ gland-like structures. Single stromal cells were multipotent as they differentiated into 4 mesodermal lineages; myogenic, adipogenic, osteoblastic and chondrogenic, suggesting that human endometrium contains a rare population of epithelial progenitor cells and mesenchymal stem cells (MSC) (2). Transplantation of freshly isolated human endometrial cells into immunocompromised mice reconstructed endometrial tissue that responded to estrogen and progesterone (3). Endometrial MSC can be prospectively isolated by co-expression of CD146 and PDGFRβ (4), but not Stro-1, a bone marrow MSC marker (5). Currently there are no known markers of endometrial epithelial progenitor cells. Endometrial cancer tissue harbours a small subpopulation of clonogenic, self-renewing, tumour-initiating cells, producing tumours that recapitulate parent tumours in histoarchitecture and differentiation markers (ERα, PR, cytokeratin, vimentin) when xenografted into mice, suggesting they are cancer stem cells. Candidate epithelial and stromal stem/progenitor cells have been identified in mouse endometrium as label retaining cells (LRC) in the luminal epithelium and perivascular cells at the endometrial-myometrial junction, respectively (6). It is likely that endometrial stem/progenitor cells play key roles in the development of gynecological diseases associated with abnormal endometrial proliferation such as endometriosis and endometrial cancer (7).

Hormone and growth factor signaling in endometrial renewal: Role of stem/progenitor cells

The human endometrium is a dynamic remodeling tissue undergoing more than 400 cycles of regeneration, differentiation and shedding during a woman's reproductive years. The co-ordinated and sequential actions of estrogen and progesterone direct these major remodeling events preparing a receptive endometrium for blastocyst implantation on a monthly basis. Adult stem/progenitor cells are likely responsible for endometrial regeneration. Functional approaches have been used to identify candidate endometrial stem/progenitor cells, as there are no specific stem cell markers. Rare populations of human endometrial epithelial and stromal colony-forming cells/units (CFU) and side population (SP) cells have been identified. Several growth factors are required for CFU activity: epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and platelet-derived growth factor BB (PDGF-BB) for both epithelial and stromal CFU, and basic fibroblast growth factor (bFGF) for stromal, but not epithelial CFU. A sub-population of human endometrial stromal cells with mesenchymal stem cell properties of CFU activity and multilineage (fat, muscle, cartilage and bone) differentiation have been isolated by their co-expression of CD146 and PDGF-receptor beta. Candidate epithelial and stromal stem/progenitor cells have been identified in mouse endometrium as rare label retaining cells (LRCs) in the luminal epithelium and as perivascular cells at the endometrial-myometrial junction, respectively. While epithelial and most stromal LRC do not express estrogen receptor alpha (Esr1), they rapidly proliferate on estrogen stimulation, most likely mediated by neighbouring Esr1-expressing niche cells. It is likely that these newly identified endometrial stem/progenitor cells may play key roles in the development of gynecological diseases associated with abnormal endometrial proliferation such as endometriosis and endometrial cancer.

Cyclical progestogens for heavy menstrual bleeding

Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical pathology, which makes medical therapy, with the avoidance of possibly unnecessary surgery, an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed. This review assesses the effectiveness of two different regimens of oral progestogens in reducing ovulatory HMB. The primary objective of this review was to investigate the effectiveness of oral progestogen therapy taken either during the luteal phase or for a longer course of 21 days in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB). We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2007), MEDLINE (1966 to April 2007) and EMBASE (1985 to April 2007). Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted. The inclusion criteria were randomised comparisons of oral progestogen therapy versus placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic causes for their heavy menstrual blood loss. Seven randomised controlled trials (RCTs) were identified that fulfilled the inclusion criteria. The review authors extracted the data independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. No RCTs comparing progestogen treatment with placebo were identified. Comparisons between oral progestogens and other medical therapies were assessed separately according to dosage regimen.Progestogen therapy during the luteal phase was significantly less effective at reducing menstrual blood loss when compared with tranexamic acid, danazol and the progesterone-releasing intrauterine system (IUS). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter with danazol treatment. Adverse events were significantly more likely with danazol when compared with progestogen treatment. Progestogen therapy from day 5 to day 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the IUS. A significantly higher proportion of norethisterone (NET) patients taking progestogens found their treatment unacceptable compared to IUS patients. However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the IUS. Progestogens administered from day 15 or 19 to day 26 of the cycle offer no advantage over other medical therapies such as danazol, tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs) and the IUS in the treatment of menorrhagia in women with ovulatory cycles. Progestogen therapy for 21 days of the cycle results in a significant reduction in menstrual blood loss, although women found the treatment less acceptable than intrauterine levonorgestrel. This regimen of progestogen may have a role in the short-term treatment of menorrhagia.

COMMENTARY: Are the Endocrine Society's Clinical Practice Guidelines on Androgen Therapy in Women Misguided? A Commentary

The Endocrine Society Clinical Guidelines on Androgen Therapy in Women (henceforth referred to as the Guidelines) do not necessarily represent the opinion held by the many health-care professionals and clinicians who are specialized in the evaluation, diagnosis, and treatment of women's health in androgen insufficiency states. The recommendations provided in the published Guidelines are neither accurate nor complete. We disagree with the therapeutic nihilism promoted by these Guidelines. The members of the Guidelines Panel (henceforth referred to as the Panel), in their own disclaimer, stated that the Guidelines do not establish a standard of care. Based on data available in the contemporary literature, on the role of androgens in women's health, we provide in this commentary a point-by-point discussion of the arguments made by the Panel in arriving at their recommendations. It is our view that the Guidelines are not based on the preponderance of scientific evidence. Health-care professionals, physicians, and scientists often disagree when determining how best to address and manage new and emerging clinical issues. This is where we stand now as we endeavor to understand the role of androgens in a woman's health and welfare. Indeed, some basic facts are not in contention. All agree that dehydroepiandrosterone sulfate (DHEA-S) production from the adrenal gland begins during the preteen years, peaks in the mid 20s, then declines progressively over time. In contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty, is sustained during a woman's peak reproductive years and declines as a woman ages, with a more rapid and steep decrease after surgical menopause. However, there are ample data to suggest that adrenal androgens play a role in the development of axillary and pubic hair, and that testosterone is critical for women's libido and sexual function. We take this opportunity to invite members of the Panel on Androgen Therapy in Women to discuss, clarify, comment, or rebut any of the points made in this Commentary. It is our goal to elevate this debate in order to provide women who are afflicted with androgen insufficiency and sexual disorders with the highest quality health care and to relieve their distress and suffering, as well as to improve their quality of life.

Subdermal implantable contraceptives versus other forms of reversible contraceptives or other implants as effective methods for preventing pregnancy

Implantable methods of contraception offer long-acting reversible contraception. Their uptake rate in comparison to other contraceptive methods, particularly in developed countries, has historically been low. To assess the contraceptive effectiveness, tolerability and acceptability of subdermal implants in comparison to other reversible contraceptive methods. Literature were identified through database searches, reference lists and individuals/organisations working in the contraceptive field. All randomised and controlled trials comparing subdermal implants with other forms of reversible contraceptives and reporting on pre-determined outcomes in women of reproductive years. Primary outcomes were pregnancy and continuation. Quality assessment of studies and data extraction were completed independently by two reviewers. A quality checklist was designed to identify general methodological and contraceptive specific factors. Study authors and pharmaceutical companies were contacted to provide additional data.Data were collected on pregnancy rates, continuation, side effects and adverse events. All nine identified trials compared different types of contraceptive implant. Eight, involving 1578 women, compared Implanon with Norplant , and one, involving 1198 women, compared Jadelle with Norplant. There was no difference between Implanon and Norplant for contraceptive effectiveness rates or continuation over 4 years. Both were highly effective methods of contraception with no pregnancies occurring in any of the trials during 26,972 and 28,108 women months of follow up respectively. The most common side-effect with Implanon and Norplant was changes in bleeding pattern. The pattern with Implanon was initially more variable, bleeding with both implants became less frequent with duration of use. After two years use the amenorrhoea rate was significantly higher with Implanon. The trials reported no significant difference in hormonal side-effects or adverse events. Implanon was significantly quicker to insert and remove than Norplant. There was no difference in contraceptive effectiveness and in continuation rates between Jadelle and Norplant. Jadelle was significantly quicker to remove than Norplant. Implanon, Norplant and Jadelle are highly effective contraceptive methods. No significant differences were found in contraceptive effectiveness or continuation. The most common side-effect with all implants was unpredictable vaginal bleeding. Time taken for removal of Implanon and Jadelle was less than that for Norplant.Although this systematic review was unable to provide a definitive answer on relative effectiveness, tolerability and acceptability of contraceptive implants in comparison to other contraceptive methods, it has raised issues around the conduct of contraceptive research.