Severity of premenstrual symptoms in a health maintenance organization population

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Rahmioglu N et al., 2023 · Nat Genet · Free full text on PubMed Central

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Steroidal contraceptives and bone fractures in women: evidence from observational studies

Lopez LM et al., 2015 · Cochrane Database Syst Rev · Free full text on PubMed Central

Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life. We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women. Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports. Selection Criteria: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture. Data Collection and Analysis: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis. MAIN We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use. AUTHORS' Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.

Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

Nnoaham KE et al., 2011 · Fertility and Sterility · Free full text on PubMed Central

Direct-to-participant feedback and awareness of bone mineral density testing results in a population-based sample of mid-aged Canadians

Kingwell E et al., 2009 · Osteoporos Int

This population-based study of mid-aged Canadians assessed awareness of diagnosis by bone mineral density (BMD) following dual-energy X-ray absorptiometry (DXA) testing and compared the effects of feedback only to the physician with direct-to-participant feedback. Poor recall of osteoporosis results was observed irrespective of the feedback destination, but direct-to-participant feedback improved recall of borderline or normal results. BMD testing provides information about fracture risk. This study assessed whether awareness of results, in a random population sample of mid-aged Canadians, differed if results were provided to physicians only or directly to participants. Prospective cohort study of 2,678 women and men aged 40-60 years from the Canadian Multicentre Osteoporosis Study. Participants completed hip and spine DXA and interviewer-administered questionnaires regarding demographics and osteoporosis risk factors. Lateral spine X-rays were conducted on those > or =50 years of age. All test results were reported to the participant, the family physician or both. Associations between BMD results, feedback destination and correct self-report results, 3 years later, were assessed using logistic regression while adjusting for potential confounders. Only 25% of men and 33% of women correctly reported their osteoporosis diagnoses. Direct-to-participant vs. physician-only reports did not improve recall of osteoporosis diagnosis but improved recall of borderline or normal BMD. Older (vs. younger) men and men with prevalent vertebral fractures demonstrated better recall of their osteoporosis diagnosis. Recall of low BMD results was poor, despite direct-to-participant feedback and even in the presence of other osteoporosis risk factors. Direct-to-participant feedback may improve awareness of borderline or normal BMD results.

Menstrual cycle symptom variation in a community sample of women using and not using oral contraceptives

Sveinsdóttir H et al., 2000 · Acta Obstet Gynecol Scand

The prevalence of significant symptom change (symptom cyclicity) prospectively rated over multiple menstrual cycles has not been established in a non-clinical population. Seventy-three women charted 57 symptoms over 2-6 menstrual cycles each. Symptoms, and summarized symptom scores within seven symptom groups, were tested for changes between the follicular phase and the luteal phase of each cycle. Recurrent symptom cyclicity over multiple cycles within individuals was ascertained and the stability between cycles of mean symptom scores for both the follicular phase and the luteal phase. Forty-five percent of the participants experienced cyclicity over multiple cycles in at least one symptom and 23% in at least one symptom group. Eighteen percent of the participants consistently reported a higher symptom score during the luteal phase compared to the follicular phase (a PMS-like pattern) in all symptoms in which they experienced a change. The remaining 27% experienced a varying direction of change in the same symptom between cycles, or consistently experienced a lower symptom score during the luteal phase (a reverse PMS-like pattern) of the cycles they charted. Recurrent cyclicity was experienced by 16% of the participants in one symptom; in two symptoms by 15%; in 3 8 symptoms by 14%; in one symptom group by 19% and in two symptom groups by only 4% of participants. Average symptom severity did not vary significantly between cycles. Due to the varied direction of symptom severity change over multiple cycles, prospective daily ratings are necessary to achieve a true picture of menstrual related symptom cyclicity in the general population.

An exploratory dimensional approach to premenstrual manifestation of obsessive-compulsive disorder symptoms: a multicentre study

Moreira L et al., 2013 · Journal of psychosomatic research

In women with obsessive-compulsive disorder (OCD), symptom severity appears to fluctuate over the course of the menstrual cycle. The objective of this paper was to compare female OCD patients with and without premenstrual worsening of obsessive-compulsive symptoms (OCS), in terms of the clinical characteristics of OCD. This was a cross-sectional study involving 455 women with OCD, of whom 226 (49.7%) had experienced premenstrual OCS worsening and 229 (50.3%) had not (PMOCS-worse and PMOCS-same groups, respectively). Data were collected with the original and dimensional versions of the Yale-Brown obsessive-compulsive scale, as well as with the Beck Depression Inventory (BDI) and Beck anxiety inventory (BAI). We found significant differences between the PMOCS-same and PMOCS-worse groups, the latter showing a higher frequency of suicidal ideation (P<.001), suicide attempts (P=.027), current use of selective serotonin reuptake inhibitors (P=.022), lifetime use of mood stabilisers (P=.015), and sexual/religious obsessions (P<.001; OR=1.90), as well as higher scores on the BDI (P<.001) and BAI (P<.001). Underscoring the fact that OCD is a heterogeneous disorder, there appears to be a subgroup of female OCD patients in whom the premenstrual period is associated with a higher frequency of sexual/religious obsessions, depression, anxiety, and suicidality. This might be attributable to hormonal fluctuations. Further studies are warranted in order to investigate this hypothesis by evaluating such patients at different phases of the menstrual cycle, as well as measuring hormonal levels.

Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive Review

Handy AB et al., 2022 · Harv Rev Psychiatry · Free full text on PubMed Central

LEARNING After participating in this activity, learners should be better able to:• Discuss and outline the general and overlapping effects of the menstrual cycle on women's mental health. A growing body of research demonstrates menstrual cycle-dependent fluctuations in psychiatric symptoms; these fluctuations can therefore be considered as prevalent phenomena. Possible mechanisms underlying these fluctuations posit behavioral, psychological, and neuroendocrine influences. Recent reviews document cyclic exacerbation of symptoms and explore these mechanisms in the context of specific and often single disorders. The question remains, however, as to whether there are general and overlapping effects of the menstrual cycle on women's mental health. To address this gap, we synthesized the literature examining the exacerbation of a variety of psychiatric symptoms across the menstrual cycle in adult women. Results show that the premenstrual and menstrual phases are most consistently implicated in transdiagnostic symptom exacerbation. Specifically, strong evidence indicates increases in psychosis, mania, depression, suicide/suicide attempts, and alcohol use during these phases. Anxiety, stress, and binge eating appear to be elevated more generally throughout the luteal phase. The subjective effects of smoking and cocaine use are reduced during the luteal phase, but fewer data are available for other substances. Less consistent patterns are demonstrated for panic disorder, symptoms of posttraumatic stress disorder, and borderline personality disorder, and it is difficult to draw conclusions for symptoms of generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and trichotillomania because of the limited data. Future research should focus on developing standardized approaches to identifying menstrual cycle phases and adapting pharmacological and behavioral interventions for managing fluctuations in psychiatric symptoms across the menstrual cycle.

Lowered Plasma Steady-State Levels of Progesterone Combined With Declining Progesterone Levels During the Luteal Phase Predict Peri-Menstrual Syndrome and Its Major Subdomains

Roomruangwong C et al., 2019 · Frontiers in Psychology · Free full text on PubMed Central

It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle are associated with premenstrual syndrome (PMS). To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS considering different diagnostic criteria for PMS. Forty-one women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21, and 28 to assay oestradiol and progesterone. We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e., depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including that of the American College of Obstetricians and Gynecologists (ACOG). Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone. A significant increase in menstrual-cycle related symptoms can best be conceptualized as "peri-menstrual syndrome" and may result from insufficient progesterone production (relative corpus luteum insufficiency), which, in part may result from lowered oestradiol production indicating suboptimal pre-ovulatory follicular development.