Caffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis. Four hundred and seventy three women, ages 18-44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors. There were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk. This study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.
Catholic bioethicists have extensively addressed extrauterine tubal pregnancies, which represent the great majority of ectopic pregnancies. However, additional management options have been developed for the other 7-10 percent of ectopic pregnancies. Using two cases of interstitial pregnancy and two cases of cesarean scar pregnancy (CSP) seen at a Catholic tertiary care center, this article discusses options including expectant management, systemic methotrexate, intragestational methotrexate, intragestational potassium chloride, uterine artery embolization, dilation and curettage (D&C), vasopressin use, cornuostomy, cornual wedge resection, CSP evacuation, CSP scar excision, CSP salvage, and hysterectomy. Cornual wedge resection, vasopressin use, and CSP scar excision are morally acceptable; less clearly licit are aspiration of gestational sac contents, cornuostomy, gestational excision for CSPs, and methotrexate. Certainly illicit are any techniques leading to direct abortion such as D&Cs on live embryos or fetuses, double-balloon catheter placement, and use of potassium chloride.
An ectopic pregnancy is any pregnancy outside the uterus. These are dangerous because the pregnancy can burst out of its abnormal location and cause life-threatening internal bleeding. Most are in the part of the fallopian tube outside the uterus, but there are other types, including interstitial pregnancies (located in the part of the tube tunneling through the uterine wall) and cesarean scar pregnancies (buried in the uterine scar where the cut for a C-section was made). This article lists the ways that physicians prevent women from dying from interstitial and cesarean scar pregnancies and proposes which treatments are morally acceptable.
Vieira-Baptista P et al., 2018·Case Reports in Women's Health
•Vulvodynia affects at least 6% of women, and can be found at any age and in all ethnic groups.•The diagnosis is one of exclusion but is very often missed.•Women with vulvodynia are frequently misdiagnosed as having vaginismus.•Failure to make the diagnosis often leads to irrelevant or deleterious examinations and treatments.
Kim YS et al., 2018·Journal of Neurogastroenterology and Motility
Because of the sex-gender differences that are shown in a diversity of physiological and psychological factors, it can be speculated that the clinical presentation of symptoms as well as treatment strategies in women and men with irritable bowel syndrome (IBS) may differ. Studies have revealed that IBS is more common in women than men. As for the IBS subtype, IBS with constipation is significantly more prevalent among women than men. Sex hormones and gender differences may play important roles in the pathophysiology of IBS. However, its pathophysiologic mechanisms still remain largely unknown, and therapeutic implications are limited. Moreover, women IBS patients have been reported to feel more fatigue, depression, anxiety, and lower quality of life than men IBS patients. Furthermore, there has been evidence of differences in the appropriate treatment efficacy to IBS in men and women, although relatively few men are enrolled in most relevant clinical trials. A more sex-gender-oriented approach in the medical care setting could improve understanding of heterogeneous patients suffering from IBS. An individualized and multicomponent approach including sex and gender issues might help improve the treatment of IBS.
Chandrasekaran S et al., 2018·The Obstetrician & Gynaecologist
Key content The risk factors for metabolic syndrome include central obesity, hypertension, atherogenic dyslipidaemia and insulin resistance. Metabolic syndrome affects 33% of women with polycystic ovary syndrome (PCOS) and has been less well researched than other features such as infertility, anovulation and hirsutism. Consequences of metabolic syndrome include cardiovascular disease, type II diabetes, cancer, sleep apnoea and psychological problems. Cardiometabolic risk screening involves obtaining data on smoking history, weight, body mass index, waist circumference, blood pressure, lipid profile, and taking an oral glucose tolerance test. Management of metabolic syndrome should focus on risk factors and individual components. Lifestyle modification is the only recommended intervention at present. Learning objectives To know the pathogenesis and consequences of metabolic syndrome in women with PCOS. To understand the diagnostic criteria and screening procedures for metabolic syndrome. To learn how to manage metabolic syndrome in women with PCOS. Ethical issues Potential preventive long‐term duration of therapy and unwarranted adverse effects. Advocating bariatric surgery without availability of robust evidence in PCOS women.
DiagnosticsLow-Dose Naltrexone Therapeutic ReviewOpioid Antagonist TherapyOff-Label Drug Applications
Open Access
Naltrexone and naloxone are classical opioid antagonists. In substantially lower than standard doses, they exert different pharmacodynamics. Low-dose naltrexone (LDN), considered in a daily dose of 1 to 5 mg, has been shown to reduce glial inflammatory response by modulating Toll-like receptor 4 signaling in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade. Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn's disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer. In a dosing range at less than 1 μg per day, oral naltrexone or intravenous naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling. This dose is termed ultra low-dose naltrexone/naloxone (ULDN). It has been of use in postoperative control of analgesia by reducing the need for the total amount of opioids following surgery, as well as ameliorating certain side-effects of opioid-related treatment. A dosing range between 1 μg and 1 mg comprises very low-dose naltrexone (VLDN), which has primarily been used as an experimental adjunct treatment for boosting tolerability of opioid-weaning methadone taper. In general, all of the low-dose features regarding naltrexone and naloxone have been only recently and still scarcely scientifically evaluated. This review aims to present an overview of the current knowledge on these topics and summarize the key findings published in peer-review sources. The existing potential of LDN, VLDN, and ULDN for various areas of biomedicine has still not been thoroughly and comprehensively addressed.
Iversen L et al., 2018·BMJ (Clinical research ed.)
To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer. Prospective, nationwide cohort study. Denmark, 1995-2014. All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.
Contraception/ComparisonMental Health Side EffectsSuicidality RiskCross-Sectional Survey
The association of suicide with the use of oral contraceptives (OC) is unknown in the Asian population. We aimed to evaluate the association of OC use and suicidal behavior in a nationally representative population of Korean women. Of the 44,501 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20 years or older who had completed information on OC use and suicidal behavior were included. Women with a history of cancer were excluded. Compared to non-users of OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a multivariable logistic regression among OC users, with testing of the interaction term of OC use and history of depression. We also conducted a stratified analysis by history of depression. A total of 4,067 women (14.0%) reported they had suicide ideations or had attempted suicide, respectively. OC use was associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00-1.24) after adjustments for age, demographic factors, age of menarche, and lifestyle behaviors. When stratified by history of depression diagnosis, ORs linearly increased as the total duration of OC use lengthened among women with a history of depression; however, women without a history of depression showed peaked OR at 4to 12-month use. There is an increased association between OC use and suicidality and the pattern of the relationship differs depending on whether there is a history of depression.
Menstrual CycleClassification SystemsFIGO StandardsAbnormal Uterine Bleeding
Open Access
The International Federation of Gynecology and Obstetrics (FIGO) systems for nomenclature of symptoms of normal and abnormal uterine bleeding (AUB) in the reproductive years (FIGO AUB System 1) and for classification of causes of AUB (FIGO AUB System 2; PALM-COEIN) were first published together in 2011. The purpose was to harmonize the definitions of normal and abnormal bleeding symptoms and to classify and subclassify underlying potential causes of AUB in the reproductive years to facilitate research, education, and clinical care. The systems were designed to be flexible and to be periodically reviewed and modified as appropriate. To review, clarify, and, where appropriate, revise the previously published systems. To a large extent, the process has been an iterative one involving the FIGO Menstrual Disorders Committee, as well as a number of invited contributions from epidemiologists, gynecologists, and other experts in the field from around the world between 2012 and 2017. Face-to-face meetings have been held in Rome, Vancouver, and Singapore, and have been augmented by a number of teleconferences and other communications designed to evaluate various aspects of the systems. Where substantial change was considered, anonymous voting, in some instances using a modified RAND Delphi technique, was utilized.
Bone HealthProgesterone and Ovulation RoleBone Health ConsequencesBeyond Estrogen Paradigm
Open Access
Lete I et al., 2018·European journal of obstetrics, gynecology, and reproductive biology
To assess the impact of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain on endometriosis-associated pelvic pain. Multicenter, open-label, non-comparative clinical trial in a representative sample of women with endometriosis-associated pelvic pain. In total, 398 patients with a mean age of 34.6 ± 7.2 years were treated with a combination of N-acetyl cysteine, alpha lipoic acid and bromelain for 6 months. At baseline, 92.7% of the patients had pain intensity > 4 on the visual analogue scale (VAS); at 3 months of treatment, this percentage decreased to 87.2% (p = 0.074) and at 6 months the percentage was 82.7% (p < 0.05). Women with endometriosis who wish to become pregnant and are treated with a preparation containing N-acetyl cysteine, alpha lipoic acid and bromelain experienced a significant improvement in endometriosis-associated pelvic pain and required lower intake of rescue analgesics.
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"ART in Europe, 2014: results generated from European registries by ESHRE"
source_file: "eshre-eim-2014-source.pdf"
"10.1093/humrep/dey242"
"Human Reproduction, pp. 1-16, 2018"
16
extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
review_flags: 3
"Ch. De Geyter, C. Calhaz-Jorge, M.S. Kupka, C. Wyns, E. Mocanu, T. Motrenko, G. Scaravelli, J. Smeenk, S. Vidakovic, V. Goossens"
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Deep dyspareunia occurs in half of women with endometriosis, a condition present in 10% of reproductive-age women and associated with negative effects on sexual quality of life (SQoL). However, women with endometriosis can have other clinical factors (eg, superficial dyspareunia, other pelvic pains, and psychological or pain conditions) possibly affecting SQoL. To determine whether deep dyspareunia is associated with SQoL in women with endometriosis, independent of potential confounders. This study involved a prospective patient registry of women at a tertiary-level referral center for endometriosis and pelvic pain. Inclusion criteria were (i) referrals to the center recruited into the registry from January 2014 through December 2016 and (ii) subsequent surgery at the center with histologic confirmation of endometriosis. Exclusion criteria included menopausal status, age at least 50 years, never sexually active, or did not answer dyspareunia or SQoL questions. Bi-variable tests and multiple linear regression analysis were performed. SQoL measured by the 5-item sexual intercourse subscale of the Endometriosis Health Profile-30 (EHP-30) modular questionnaire (0-100%, with higher scores indicating worse SQoL). Consent rate for the prospective registry was 87%; 277 women met the study criteria (mean age = 34.2 ± 7.1 years). Most women had stage I to II endometriosis at time of surgery (64%), with the remaining having stage III to IV endometriosis. Through regression analysis, worse SQoL (higher EHP-30 sexual intercourse subscale score) was more severe deep dyspareunia (P < .0001), more severe superficial dyspareunia (P < .0001), increased depression (P < .001), higher pain catastrophizing (P = .04), bladder pain syndrome (P = .02), heterosexual orientation (P < .001), and new referral status (P = .02). In women with endometriosis at a tertiary referral center, more severe deep dyspareunia was associated with worse SQoL, independent of superficial dyspareunia, psychological comorbidities, and other potential confounders. Shum LK, Bedaiwy MA, Allaire C, et al. Deep Dyspareunia and Sexual Quality of Life in Women With Endometriosis. Sex Med 2018;6:224-233.
Osborne LM, 2018·Obstetrics and gynecology clinics of North America
Postpartum psychosis is a psychiatric emergency that affects 1 to 2 per 1000 women. Key clinical features include mood fluctuation, abnormal thoughts or behaviors, and confusion. Women with a history of bipolar disorder are at heightened risk, as are first-time mothers; current research on the causes focuses on biological triggers, such as immune dysregulation. Women with postpartum psychosis require inpatient hospitalization and should be treated with lithium, antipsychotics, and benzodiazepines.
A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed. A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring. PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI-conceived offspring beyond 28 days after birth. Physical and psychosocial health. The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full-text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. Growth, vision, and hearing of ICSI and SC offspring also appear comparable, although important differences in general physical health, and particularly metabolic and reproductive health have been described, including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers. Whilst neurodevelopment, growth, vision, and hearing appear similar between ICSI and SC children, evidence suggests differences in general physical health, and metabolic and reproductive endpoints. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSI-conceived young adults are required.
Contraception/ComparisonEgg Freezing TrendsOocyte CryopreservationUK Regulation and Statistics
To determine the live birth rate for patients who chose to undergo treatment with Restorative Reproductive Medicine (RRM) after previous IVF (includes ICSI). To look at birth outcomes with RRM after IVF, particularly rates of twin and higher order pregnancies, premature birth, low birth weight, and potential cost savings achieved with RRM. Two outpatient clinics in Ireland providing advanced RRM treatment of infertility. All patients presenting between January 2004 and January 2010, with a history of infertility and previous IVF treatment were included if they proceeded beyond the initial consultation and began treatment. Main outcome is live birth per couple calculated using life table analysis. 403 patients met the study criteria, among which 74 had a subsequent live birth. These women had significant negative predictive characteristics for advanced reproductive age (average 37.2 years), an average of 5.8 years of infertility with 2.1 (range 1-9) previous IVF attempts, with only 5% having previously had a live birth from IVF. Despite these undesirable prognostic indicators, the overall RRM live birth rate was 32.1% (crude 18.4%). Women aged 35-38 had a live birth rate of 37.5% (crude 23.6%) and older women over 40 had a live birth rate of 27.4% (crude 16.0%). The average birth weight was 3374g (7lb 7oz) with 92% being born at 37+ weeks and no very low birth weight babies. There was only one twin pregnancy in the study population; the potential health care savings for avoidable multiple pregnancies in these patients was estimated at £205 672 (USD$284 915). Patients who have already tried IVF can achieve comparable live birth outcomes with RRM compared to another cycle of IVF. RRM has a low risk of twin or multiple births, and very good neonatal outcomes with a potential cost savings to the health care system.
To summarize best available prospective data on typical and perfect use effectiveness of fertility awareness-based methods for avoiding pregnancy. We conducted a systematic review of studies published in English, Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. We reviewed 8,755 unique citations and included 53 studies that contained 50 or greater women using a specific fertility awareness-based method to avoid pregnancy, calculated life table pregnancy probabilities or Pearl rates, and prospectively measured pregnancy intentions and outcomes. We systematically evaluated study quality. TABULATION, INTEGRATION, Of 53 included studies, we ranked 0 high quality, 21 moderate quality, and 32 low quality for our question of interest. Among moderate-quality studies, first-year typical use pregnancy rates or probabilities per 100 11.2-14.1 for the Standard Days Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method, 4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double-check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus Method. First-year perfect use pregnancy rates or probabilities among moderate-quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method, 1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method, 0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor. Studies on the effectiveness of each fertility awareness-based method are few and of low to moderate quality. Pregnancy rates or probabilities varied widely across different fertility awareness-based methods (and in some cases, within method types), even after excluding low-quality studies. Variability across populations studied precludes comparisons across methods.
This issue of Current Medical Research (CMR) includes studies that provide evidence that use of natural family planning (NFP) can be helpful for subfertile couples wishing to achieve a pregnancy, the effectiveness of a method of NFP during breastfeeding, and the effects of using NFP on marital relationships. This review also includes evidence on predicting the sex of a baby by timing intercourse, evidence that brain injuries can be reflected in changes in the menstrual cycle, and that women prefer methods of family planning that have no side effects. The issue ends with an in-depth review of new technologies that aid in the use of NFP. Topics covered include subfertile couples, breastfeeding, marriage, predicting the sex of a baby, brain injuries, and new technologies.
Ethics/PhilosophyHumanae Vitae 50th AnniversaryNFP Movement MilestonesReproductive Ethics Editorial
Photobiomodulation (PBM) is a treatment method based on research findings showing that irradiation with certain wavelengths of red or near-infrared light has been shown to produce a range of physiological effects in cells, tissues, animals and humans. Scientific research into PBM was initially started in the late 1960s by utilizing the newly invented (1960) lasers, and the therapy rapidly became known as "low-level laser therapy". It was mainly used for wound healing and reduction of pain and inflammation. Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device, and in fact, some authors insisted that lasers were essential to the therapeutic benefit. Collimated, coherent, highly monochromatic beams with the possibility of high power densities were considered preferable. However in recent years, non-coherent light sources such as light-emitting diodes (LEDs) and broad-band lamps have become common. Advantages of LEDs include no laser safety considerations, ease of home use, ability to irradiate a large area of tissue at once, possibility of wearable devices, and much lower cost per mW. LED photobiomodulation is here to stay.
Menstrual CycleLuteinized Unruptured Follicle SyndromeNSAIDs and OvulationFollicular Development and Ovulation
To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Müllerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.
AndrologyInsulin Resistance and Testicular FunctionMale Insulin SensitivityMetabolic Syndrome Hormonal Effects
Open Access
A cohort of 141 males (18-80 yo, 42.9 ± 12.9) strongly suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) was ≥150 mg/dL and Non-Insulin Resistant (NIR) when SSPG was <150 mg/dl; similarly, the subjects were labeled as Hypogonadal (HYPOG) when total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when total testosterone was >3.0 ng/mL. Two out of three subjects turned out to be IR, while around one in four subjects were HYPOG. Contingency analysis indicated a significant interdependence between insulin resistance and hypogonadism (chi-square was 4.69, p = 0.0303). Age (>43 yo) predicted hypogonadism (AUROC 0.606, p = 0.0308). Twice as many HYPOG subjects were IR as compared with EUG subjects. Also, HYPOG subjects exhibited higher SSPG values as compared with EUG subjects. Statistically, neither Weight nor BMI predicted hypogonadism, while Waist Circumference (>110 cm) was only a mediocre predictor (AUROC 0.640, p = 0.009). SSPG (>224 mg/dL) on the other hand, was the best predictor of hypogonadism (AUROC 0.709, p = 0.002), outperforming Waist Circumference (half of the subjects with an SSPG >224 mg/dL were HYPOG). Age did not predict insulin resistance, while Weight (>99 kg), BMI (>29), and especially, Waist Circumference (>99 cm, AUROC 0.812, p < 0.0001) were all predictors of insulin resistance. Almost 90% of the subjects with a waist circumference >99 cm was IR. As a logical consequence of the selection criteria (various clues suggesting insulin resistance), most subjects with normal weight in this cohort were IR (53.3%) while 20% were HYPOG. On the other hand, 13.6% of the obese subjects were NIR, and 2 out of 3 of them were both NIR and EUG. In conclusion, Waist Circumference predicted both insulin resistance (>99 cm) and hypogonadism (>110 cm), suggesting that the first hit of abdominal obesity is insulin resistance and the second hit is male hypogonadism. Normal weight did not protect from IR, while a relevant proportion of obese subjects were NIR (with 2/3 being also EUG).
InfertilityPlatelet-Rich Plasma in GynecologyPRP TherapyPRP Clinical Applications
Open Access
The purpose of this paper is to review the current clinical uses of platelet-rich plasma (PRP) in the field of gynecology. All relevant articles published from January 2000 to December 2017 were reviewed and analyzed. The articles on PRP in the field of gynecology were mainly case series, pilot studies, or case reports. PRP is currently considered a new therapeutic modality for some disorders that are refractory to conventional drugs.
Metyas SK et al., 2018·Current Rheumatology Reviews
ConclusionFibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. A significant number of fibromyalgia patients do not respond adequately to the current drugs approved by the Food and Drug Administration (FDA) for fibromyalgia treatment including pregabalin, milnacipran, duloxetine. Thus, there is still a need for adjunctive therapies. Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. Two small prospective pilot studies have previously shown that treatment with low dose naltrexone may be an effective, safe, and inexpensive treatment for fibromyalgia. This prospective study lends further support to the preliminary body of evidence that naltrexone is a well tolerated and likely effective treatment option in the community setting. Further large prospective controlled trials are still needed.
Fertility AwarenessQuarterly Evidence SummaryMethod Comparison UpdatesReproductive Health Digest
Natural family planning (NFP) methods have served many generations well, and in particular, the symptothermal or symptohormonal methods. The comparison of daily mucus and temperature records for individual cycles with daily hormone measurements, which is now possible, shows that some of the assumptions underlying NFP may not be completely accurate. The various methods are inadvertently depending on an element of chance, which, of course, cannot be known by the NFP user. However, it is statistically inevitable that such errors will result eventually in an unexpected pregnancy, and these discrepancies are the likely reason for the method failures. Further research and integration of home hormone measurements with NFP symptoms are needed.
Traditional NFP methods, based on the observations of temperature, mucus, and luteinizing hormone, can work well. However, these data are sometimes difficult to interpret, and significant changes in the variables are sometimes "missing" from some cycles. Changes in these variables are elicited by the estrogen and progesterone released from the ovaries. It follows that the direct measures of events in the ovaries are the levels of estrogen and progesterone or their derivatives in blood or urine. Measurements of urinary derivatives of estrogen and progesterone can be used to monitor the ovaries directly and are clearer indicators than traditional NFP methods.
Ethics/PhilosophyHumanae Vitae Anniversary ReflectionNFP Science Progress ReviewReproductive Ethics Editorial
This review's purpose is to highlight evidence that oral micronized progesterone (progesterone) is effective for hot flushes and night sweats (vasomotor symptoms, VMS), improves sleep and is likely safe in menopausal women (who are more than 1 year since last menstruation). Methods include randomized controlled clinical trials (RCT) supplemented with basic science, population and observational data as needed. The barrier to use of progesterone is lack of awareness that safety concerns with estrogen-including 'menopausal hormone therapy' (MHT) are not applicable to progesterone. In a single 3-month RCT, progesterone (300 mg at bedtime) was effective treatment of VMS in 133 healthy menopausal women. It caused an overall 55% VMS decrease, no withdrawal-related VMS rebound and a greater VMS decrease in 46 women with ≥50 moderate-intense VMS/week. Progesterone is equally or more effective than estradiol in improving cardiovascular endothelial function and caused no cardiovascular safety concerns in a 3-month RCT. An 8-year prospective cohort study (E3N) in more than 80 000 menopausal women showed progesterone prevented breast cancer in estrogen-treated women. Multiple RCTs confirm that progesterone (300 mg daily at bedtime) does not cause depression and improves deep sleep. In conclusion, progesterone effectively treats VMS, improves sleep and may be the only therapy that symptomatic women, who are menopausal at a normal age and without osteoporosis, need.
Bone HealthProgesterone TherapyBone FormationBone Mineral Density Impact
Open Access
Estradiol (E2) is women's dominant 'bone hormone' since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent the rapid (3-week) bone resorption that causes most adult BMD loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone (P4) is E2's physiological partner, collaborating with E2 in every cell/tissue; its bone 'job' is to increase P4-receptor-mediated, slow (3-4 months) osteoblastic new bone formation. When menstrual cycles are normal length and normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically normal cycles commonly have ovulatory disturbances (anovulation, short luteal phases) and low P4 levels; these are more frequent in teen and perimenopausal women and increased energy insufficiency, emotional/social/economic threats and illness. Meta-analysis shows that almost 1%/year spinal BMD loss occurs in those with greater than median (∼31%) of ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures requires the reversal of stressors, detection and treatment of teen-to-perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized progesterone. Low 'Peak Perimenopausal BMD' is likely the primary risk for fragility fractures in later life. Progesterone plus estradiol or other antiresorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. Randomized controlled trials are still needed to confirm progesterone's important role in women's bone formation.
Menstrual CycleDietary Minerals and Ovulatory FunctionMicronutrient InfluenceDietary Mineral Deficiency
Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.
Clavijo RI et al., 2018·Translational andrology and urology
Practitioners of male reproductive and sexual medicine must have an intimate understanding of the physiology of male reproductive endocrinology, as such a knowledge is the cornerstone on which hormonal treatments are based. In this review, we highlight what is known about male reproductive endocrine physiology and the various control mechanisms for the system. We also discuss the limitations of our current understanding of the reproductive physiology. We hope that this review is helpful for male reproductive medicine practitioners in understanding the principles on which hormonal treatments are based.
InfertilityPhysical Activity and FecundabilityEAGeR Trial Secondary AnalysisExercise and Conception Rates
Open Access
Is physical activity (PA) associated with fecundability in women with a history of prior pregnancy loss? Higher fecundability was related to walking among overweight/obese women and to vigorous PA in women overall. PA may influence fecundability through altered endocrine function. Studies evaluating this association have primarily utilized Internet-based recruitment and self-report for pregnancy assessment and have yielded conflicting results. STUDY DESIGN, SIZE, This is a secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a multisite, randomized controlled trial of preconception-initiated low-dose aspirin. PARTICIPANTS/MATERIALS, SETTING, Healthy women (n = 1214), aged 18-40 and with 1-2 prior pregnancy losses, were recruited from four US medical centers. Participants were followed for up to six menstrual cycles while attempting pregnancy and through pregnancy for those who became pregnant. Time to hCG detected pregnancy was assessed using discrete-time Cox proportional hazard models to estimate fecundability odds ratios (FOR) adjusted for covariates, accounting for left truncation and right censoring. Main The association of walking with fecundability varied significantly by BMI (P-interaction = 0.01). Among overweight/obese women, walking ≥10 min at a time was related to improved fecundability (FOR = 1.82, 95% CI: 1.19, 2.77). In adjusted models, women reporting >4 h/wk of vigorous activity had significantly higher fecundability (FOR = 1.69, 95% CI: 1.24, 2.31) compared to no vigorous activity. Associations of vigorous activity with fecundability were not significantly different by BMI (P-interaction = 0.9). Moderate activity, sitting, and International Physical Activity Questionnaire (IPAQ) categories were not associated with fecundability overall or in BMI-stratified analyses. LIMITATIONS, Some misclassification of PA levels as determined by the short form of the IPAQ is likely to have occurred, and may have led to non-differential misclassification of exposure in our study. Information on diet and change in BMI was not collected and may have contributed to some residual confounding in our results. The generalizability of our results may be limited as our population consisted of women with a history of one or two pregnancy losses. These findings provide positive evidence for the benefits of PA in women attempting pregnancy, especially for walking among those with higher BMI. Further study is necessary to clarify possible mechanisms through which walking and vigorous activity might affect time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors report no conflicts of interest in this work. #NCT00467363.
Ferrero S et al., 2018·Expert opinion on pharmacotherapy
Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects. The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials. Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.
Bone HealthVertebral Morphometry MethodsVertebral Fracture AssessmentOsteoporotic Fracture Classification
We read with interest the editorial by Cummings and Eastell,1 A History of Pivotal Advances in Clinical Research in Bone and Mineral Diseases, published in a recent issue of the JBMR. In discussing such advances, they include spinal morphometry, and specifically refer to and illustrate the Genant semiquantitative (GSQ) paradigm,2 although also referring to the algorithm-based qualitative (ABQ) method3 of vertebral evaluation in the diagnosis of osteoporotic vertebral fractures (OVFs). Although in its day the GSQ method was a credible attempt at structured reporting, recent data suggest that GSQ grade 1 lesions, the most common, relate less well to bone density and fracture risk than comparable fractures diagnosed using the ABQ tool.4-6 Although morphometric methods may serve for understanding the epidemiology of osteoporotic fractures in large populations, it is much less certain that the GSQ method provides a basis for the care of individual patients. In a multidisciplinary context such as is served by this Journal, the endorsement of the GSQ method by the authors, without qualification, may well prove misleading. It is potentially invalid at the bedside and this should have been made explicit. We have observed a reluctance to give the presence of one or more vertebral fractures the importance they should be accorded because of confusion and ambiguity in the descriptive criteria and terminology used (eg, “wedging,” “deformity”) to define them. Perhaps the lack of a clear understanding of what might or might not constitute an OVF contributes to this disarray among radiologists and clinicians alike, again as noted recently by Szulc.7 Most of the many authors describing or reviewing “systems of morphometry,”8-12 such as in the current ASBMR primer,10 have cautioned that they are only to be used for epidemiological purposes. Moreover, most such reviews caution that positive findings should ideally be re-assessed by an “expert.” The danger, recognized by such constraints, is that of false-positive diagnoses from the clinical use of morphometry. In our experience, it is all too common for the iconic diagram provided by Dr. Genant to serve as a guide for the clinical evaluation of spinal images when that was not its intent. In the relevant article, Genant and colleagues2 were at pains to emphasize the importance of recognizing end-plate damage as evidence of OVF, but it has proved deceptively simple for readers to see only the diagram which Cummings and Eastell1 reproduce without noting these constraints. Historically the GSQ method was proposed as an attempt at structured diagnosis in fracture evaluation when such a concept was uncommon. Nevertheless it needs to be seen in perspective and it may have now outlived its usefulness. A great amount of admirable effort has gone into a structured understanding and diagnosis of atypical femoral fractures by the ASBMR.13 Those are, however, very rare events. Perhaps it is time to develop a comparable understanding of the much more common problem of OVF diagnosis to an extent the evidence allows. A taxonomy of such lesions is overdue. At present there are large differences in reported OVF incidence and prevalence for any given population. That fact probably reflects, at least in part, the method of diagnosis used, as much as any real insights into disease. None.
Reproductive EndocrinologyHormonal Predictors of DeficiencyPreovulatory-Luteal Phase RelationshipsCycle Hormone Pattern Analysis
Open Access
Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women.
Observational study.
Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.
Reproductive EndocrinologySteroid Hormones and BrainMood and Cognitive FunctionHormonal Transition
Open Access
Sex hormones significantly impact women's lives. Throughout the different stages of life, from menarche to menopause and all stages in between, women experience dramatic fluctuations in the levels of progesterone and estradiol, among other hormones. These fluctuations affect the body as a whole, including the central nervous system (CNS). In the CNS, sex hormones act via steroid receptors. They also have an effect on different neurotransmitters such as GABA, serotonin, dopamine, and glutamate. Additionally, studies show that sex hormones and their metabolites influence brain areas that regulate mood, behavior, and cognitive abilities. This review emphasizes the benefits a proper hormonal balance during the different stages of life has in the CNS. To achieve this goal, it is essential that hormone levels are evaluated considering a woman's age and ovulatory status, so that a correct diagnosis and treatment can be made. Knowledge of steroid hormone activity in the brain will give women and health providers an important tool for improving their health and well-being.
Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture. This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment. The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis. ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.
Perimenopause/MenopauseBone Density Loss AssociationNight Sweats and BMD ChangesCanadian Multicentre Osteoporosis
Open Access
Wong EMM et al., 2018·Int J Environ Res Public Health
Women's hot flushes and night sweats, collectively called vasomotor symptoms (VMS), are maximal (79%) in late perimenopause. The evidence describing whether VMS are associated with loss of areal bone mineral density (BMD) is mixed. We examined baseline and 2-year data for 1570 randomly selected women aged 43⁻63 in the Canadian Multicentre Osteoporosis Study (CaMos), a prospective Canada-wide study; we used linear regression to assess the relationship of night sweats (VMSn) with BMD and its changes. Clinically important VMSn occurred for 12.2%. Women with VMSn were slightly younger (54.5 vs. 55.3 years, p = 0.02) and less likely to use sex steroid therapies (39.8% vs. 51.4%, p < 0.05). BMD at the lumbar spine (L1-4), femoral neck (FN) and total hip (TH) were similar between those with/without VMSn. In adjusted models, we did not find a significant association between VMSn and 2-year change in L1-4, FN and TH BMD. Age, reproductive status, weight, sex steroid therapy and smoking status were associated with 2-year change in BMD. Incident fractures over 2 years also did not differ by VMSn. Our analyses were restricted to VMSn and may not truly capture the relationship between VMS and BMD. Additional research involving VMS, bone loss and fracture incidence is needed.
Bone HealthPopulation-Based Prospective EvidenceSkeletal Health OutcomesCanadian Multicentre Study
Brajic TS et al., 2018·J Musculoskelet Neuronal Interact
To assess combined hormonal contraceptives (CHC) use and adolescent women's peak areal bone mineral density (BMD) accrual. We enrolled 527 randomly selected women across Canada (2004-6) divided by age into adolescents (16-19) and young adults (20-24) and by CHC use to ever (E-CHC)/never (N-CHC) users. At baseline and year 2 we measured height, weight, and BMD at lumbar spine (L1-4), femoral neck, and total hip sites. Interviewer-administered questionnaires addressed menarche age, cigarette and alcohol use, calcium/vitamin D intakes, physical activity and estrogen dose (≤30/>30 micrograms). Linear regression models examined associations of CHC use with 2-year BMD change adjusted for bone-related variables. Of 307 women with complete data, 229 (75%) used CHC. N-CHC adolescents gained significantly more unadjusted total hip BMD +0.012 g/cm(2)/2-y (95% C.I.: 0.001, 0.023) with similar trends at all sites. N-CHC adolescents tended to have greater mean difference +0.009 g/cm(2) (95% CI: -0.002; 0.021). In young women N-CHC, however, adjusted femoral neck BMD decreased significantly more -0.021 g/cm(2) (95%CI: -0.006; -0.036) with similar trends at other sites. BMD changes were unrelated to estrogen dose and age at starting CHC. Adolescent CHC users in a random population demonstrated less hip region peak BMD accrual than non-users. This requires randomized control trial confirmation.
Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety.
Bone HealthPremenopausal BMD DeterminantsBone Density ConsequencesCaMos Reproductive Data
Open Access
Goshtasebi A et al., 2018·Int J Environ Res Public Health
Amenorrhea is important for women's bone health. However, few have reported reproductive, anthropometric (body mass index [BMI], height) and bone health (areal bone mineral density [BMD], prevalent fractures) in a population-based study. The purposes of this cross-sectional study of women in the randomly-selected Canadian Multicentre Osteoporosis Study (CaMos) (1) to describe reproductive, demographic, anthropometric and lifestyle variables; and (2) in menstruating women, to relate reproductive and other variables to BMD at the lumbar spine (L1-4, LS), femoral neck (FN) and total hip (TH) sites and to prevalent fragility fractures. This study describes the reproductive characteristics of 1532 women aged 30⁻60 years. BMD relationships with reproductive and other variables were described in the 499 menstruating women. Mean menarche age was 12.8 years, 96% of women were parous and 95% had used combined hormonal contraceptives (CHC). Infertility was reported by 9%, androgen excess by 13%, amenorrhea by 8% and nulliparity by 4%. LS BMD was negatively associated with amenorrhea and androgen excess and positively related to current BMI and height. A later age at menarche negatively related to FN BMD. BMI and height were strongly related to BMD at all sites. Prevalent fragility fractures were significantly associated with quartiles of both LS and TH BMD.
Menstrual CycleMolimina Diagnostic UtilityPremenstrual Symptoms and OvulationDetection
Open Access
Jerilynn C Prior et al., 2018·Int J Environ Res Public Health
Approximately 33% of normal-length (21⁻35 days) cycles have subclinical ovulatory disturbances and lack sufficient progesterone, although their normal length ensures enough estrogen. Subclinical ovulatory disturbances are related to significant premenopausal spine bone loss (-0.86%/year). Molimina, non-distressing premenstrual experiences, may detect ovulation within normal-length cycles. This prospective study assessed the relationship between molimina and ovulation. After 1-cycle of daily diary and first morning urine collections, women answered the Molimina Question (MQ): "Can you tell by the way you feel that your period is coming?" and were invited to share (a) predictive premenstrual experience(s). A 3-fold increase in follicular-luteal pregnanediol levels confirmed ovulation. In 610 spontaneously menstruating women (not on hormonal contraception, mean age 31.5 ± 5.3, menarche age 12.7 ± 1.5, cycle length [CL] 29 days, MQ positive in 89%), reported premenstrual experiences which included negative moods (62%), cramps (48%), bloating (39%), and front (26%) or axillary (25%) breast tenderness. Of 432 women with pregnanediol-documented cycles, 398 (92%) were ovulatory (CL: 29 ± 5) and 34 (8%) had ovulatory disturbances (CL: 32 ± 14). Women with/without ovulatory cycles were similar in parity, body mass index, smoking, dietary restraint and the MQ; ovulatory-disturbed cycles were longer. Molimina did not confirm ovulation. A non-invasive, inexpensive ovulation indicator is needed to prevent osteoporosis.
Bone HealthPremature Spinal Bone LossHIV and Telomere ShorteningHIV Bone-Telomere Association
Open Access
Shirin Kalyan et al., 2018·Int J Environ Res Public Health
With advances in combination antiretroviral therapy (cART), people living with HIV are now surviving to experience aging. Evidence suggests that individuals living with HIV are at greater risk for low bone mineral density (BMD), osteoporosis, and fractures. Better understanding of the pathophysiology of bone health in women living with HIV (WLWH) is important for treatment strategies. The goal of this study was to explore new biological factors linked to low BMD in WLWH. Standardized BMD measures of WLWH were compared to reference values from an unselected population of women from the same geographical region of the same age range. Linear regression analysis was used to assess relationships among health-related characteristics, cellular aging (measured by leukocyte telomere length; LTL), cART, and BMD of WLWH. WLWH (n = 73; mean age 43 ± 9 years) had lower BMD Z-scores at the lumbar spine (LS) (mean difference = -0.39, p p = 0.012) relative to controls (n = 290). WLWH between 50 and 60 years (n = 17) had lower Z-scores at the LS (p = 0.008) and TH (p = 0.027) compared to controls (n = 167). Among WLWH, LS BMD was significantly associated with LTL (R² = 0.09, p = 0.009) and BMI (R² = 0.06, p = 0.042). Spinal BMD was adversely affected in WLWH. Reduction of LTL was strongly associated with lower BMD and may relate to its pathophysiology and premature aging in WLWH.
Aouache R et al., 2018·International journal of molecular sciences
Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models. We then assess the putative effects of these free radicals on the placenta and maternal endothelium. This analysis was conducted with regard to recent papers and possible therapeutic avenues.
InfertilityPreconception Carotenoid Intake and FecundabilityAntioxidant MicronutrientsEAGeR Trial Micronutrient Analysis
Although maternal nutrition may affect fecundity, associations between preconception micronutrient levels and time to pregnancy (TTP) have not been examined. We assessed the relationship between preconception fat-soluble micronutrient concentrations and TTP among women with 1-2 prior pregnancy losses. This was a prospective cohort study of 1,228 women set within the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (United States, 2007-2011), which assessed the association of preconception-initiated daily low-dose aspirin with reproductive outcomes. We measured preconception levels of zeaxanthin, cryptoxanthin, lycopene, αand β-carotene, and αand γ-tocopherol in serum. We used discrete Cox regression models, accounting for left-truncation and right-censoring, to calculate fecundability odds ratios and 95% confidence intervals. The models adjusted for age, body mass index, race, smoking, alcohol, physical activity, income, vitamin use, cholesterol, treatment arm, and study site. Serum α-carotene levels (per log unit (μg/dL) increase, fecundability odds ratio (FOR) = 1.17, 95% confidence interval (CI): 1.00, 1.36) and serum α-carotene concentrations at or above the US average (2.92 μg/dL) versus below the average (FOR = 1.21, 95% CI: 1.02, 1.44) were associated with shorter TTP. Compared with levels below the US average (187 μg/dL), γ-tocopherol concentrations at or above the average were associated with longer TTP (FOR = 0.83, 95% CI: 0.69, 1.00). The potential for these nutrients to influence fecundability deserves further exploration.
Polycystic ovary syndrome (PCOS) is the main cause of female infertility worldwide and corresponds with a high degree of comorbidities and economic burden. How PCOS is passed on from one generation to the next is not clear, but it may be a developmental condition. Most women with PCOS exhibit higher levels of circulating luteinizing hormone, suggestive of heightened gonadotropin-releasing hormone (GnRH) release, and anti-Müllerian hormone (AMH) as compared to healthy women. Excess AMH in utero may affect the development of the female fetus. However, as AMH levels drop during pregnancy in women with normal fertility, it was unclear whether their levels were also elevated in pregnant women with PCOS. Here we measured AMH in a cohort of pregnant women with PCOS and control pregnant women and found that AMH is significantly more elevated in the former group versus the latter. To determine whether the elevation of AMH during pregnancy in women with PCOS is a bystander effect or a driver of the condition in the offspring, we modeled our clinical findings by treating pregnant mice with AMH and followed the neuroendocrine phenotype of their female progeny postnatally. This treatment resulted in maternal neuroendocrine-driven testosterone excess and diminished placental metabolism of testosterone to estradiol, resulting in a masculinization of the exposed female fetus and a PCOS-like reproductive and neuroendocrine phenotype in adulthood. We found that the affected females had persistently hyperactivated GnRH neurons and that GnRH antagonist treatment in the adult female offspring restored their neuroendocrine phenotype to a normal state. These findings highlight a critical role for excess prenatal AMH exposure and subsequent aberrant GnRH receptor signaling in the neuroendocrine dysfunctions of PCOS, while offering a new potential therapeutic avenue to treat the condition during adulthood.
Fertility AwarenessCalendar and App-Based MethodsLH Surge and Cycle Length VariabilityCycle Tracking App Accuracy
The accuracy of prediction of ovulation by cycle apps and published calendar methods was determined by comparing to true probability of ovulation. A total of 949 volunteers collected urine samples for one entire menstrual cycle. Luteinizing hormone was measured to assign surge day, enabling probability of ovulation to be determined across different cycle lengths. Cycle-tracking apps were downloaded. As none provided their methodology, four published calendar-based standard days, rhythm, alternative rhythm and simple calendar method. The volunteer ovulation data was applied to the app/calendar methods to determine their accuracy. Mean cycle length was 28 days (range: 23-35); 34% of women believed they had a 28-day cycle, but only 15% did. No LH surge was seen for 99 women. Most likely day of ovulation for a 28-day cycle was day 16 (21%). Accuracy of ovulation prediction was no better than 21% by the apps. The standard days and rhythm methods were most likely to predict ovulation (70% and 89%, respectively) but had very low accuracy. Ovulation day varies considerably for any given menstrual cycle length, thus it is not possible for calendar/app methods that use cycle-length information alone to accurately predict the day of ovulation. NCT01577147. www.clinicaltrials.gov .
PregnancyHair Dye and Birth WeightChemical Exposure InteractionEnvironmental Reproductive Risk
Open Access
Limited evidences were reported about the risk of pre-pregnancy hair dye use or irregular menstruation with abnormal birth weight during pregnancy, and their joint effects were also unknown. The aim of our study was to explore whether the pre-pregnancy exposure of hair dye and irregular menstruation were associated with the risk of abnormal birth weight. We conducted a nested case-control study from a prospective cohort of 6203 pregnant women. Low birth weight study included 315 mother-infant pairs (105 LBW cases and 210 matched controls), and macrosomia study included 381 mother-infant pairs (127 macrosomia cases and 254 matched controls). Meanwhile, lifestyle information including hair dying custom and menstrual history were collected by face-to-face questionnaires and birth outcomes were extracted from the medical records. The logistic regressions models were used to analyze the join effect of irregular menstruation and hair dye use. Pre-pregnancy hair dye use was associated with increased risk of LBW (adjusted OR = 1.71, 95% CI: 1.01-2.92, P = 0.048). Irregular menstruation had high risk of LBW (adjusted OR = 2.79, 95% CI: 1.53-5.09, P = 0.001) and macrosomia (adjusted OR = 1.93, 95% CI: 1.09-3.44, P = 0.023). Additionally, in the LBW study, women who used hair dye with pre-pregnancy BMI < 18.5 kg/m(2) had higher OR than those with only one risk factor (3.07 vs 2.53, P (trend) = 0.015), and women with both hair dye use and irregular menstruation also had higher risk than those with only one factor (4.53 vs 2.07, P (trend) = 0.05). Moreover, in macrosomia study, women with irregular menstruation and pre-pregnancy BMI ≥ 24 kg/m(2) had higher risk than those with one factor (13.31 vs 2.09, P (trend) = 0.001). Our study showed that either pre-pregnancy hair dye use or irregular menstruation was associated with abnormal birth weight, especially, their joint effects could furthermore increase the risk of low birth weight infants when these two factors existed simultaneously.