Climacteric status at age 46 is associated with poorer work ability, lower 2-year participation in working life, and a higher 7-year disability retirement rate: a Northern Finland Birth Cohort 1966 study.

OBJECTIVE: To study the association between an advanced climacteric status at 46 years of age and current perceived work ability, the consequent 2-year accumulation of disability and unemployment days, and the 7-year incidence of disability pensions. METHODS: Study participants (n = 2,661) were recruited from the Northern Finland Birth Cohort 1966 study's 46-year follow-up in 2012. The participants' perceived work ability was investigated using the Work Ability Score (0-7 = poor vs 8-10 = good), along with potential covariates. Data concerning their consequent disability days, unemployment days, and disability pensions were collected from national registers. The association between their climacteric status at age 46 years, work ability, and working life participation was assessed using regression models. RESULTS: The climacteric women were more often smokers and more often had a lower level of education. The odds ratio for poor perceived work ability was 1.41 (95% CI, 1.06-1.87), and the incidence rate ratios for disability and unemployment days during the 2-year follow-up were 1.09 (95% CI, 1.07-1.11) and 1.16 (95% CI, 1.14-1.18), respectively, for the climacteric women compared with the preclimacteric women in models adjusted for smoking and education. The 7-year hazard ratio for disability pensions was 1.72 (95% CI, 1.02-2.91) for the climacteric women. CONCLUSIONS: An earlier menopausal transition is associated with poorer perceived work ability, and it predicts lower recorded work participation and a higher disability pension rate in subsequent years.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population-based case-control study.

INTRODUCTION: To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI. MATERIAL AND METHODS: We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period. RESULTS: Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23). CONCLUSIONS: This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.

Low testosterone at age 31 associates with maternal obesity and higher body mass index from childhood until age 46: A birth cohort study.

BACKGROUND: Low testosterone (T) levels in men associate with increased risks of obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases. However, most studies are cross-sectional with follow-up-time < 10 years, and data on early growth are limited. OBJECTIVE: To compare prenatal factors and body mass index (BMI) development from birth to age 46 in relation to low T at age 31. MATERIALS AND METHODS: Men with low T (T < 12.1 nmol/L, n = 132) and men with normal T at age 31 (n = 2561) were derived from the Northern Finland Birth Cohort 1966. Prenatal factors, longitudinal weight and height data from birth to age 14, and cross-sectional weight and height data at ages 31 and 46, and waist-hip-ratio (WHR) and T levels at age 31 were analyzed. Longitudinal modeling and timing of adiposity rebound (AR, second BMI rise at age 5-7 years) were calculated from fitted BMI curves. Results were adjusted for mother's pre-pregnancy BMI and smoking status, birth weight for gestational age, alcohol consumption, education level, smoking status, and WHR at age 31. RESULTS: Neither gestational age nor birth weight was associated with low T at age 31; however, maternal obesity during gestation was more prevalent among men with low T (9.8% vs. 3.5%, adjusted aOR: 2.43 [1.19-4.98]). Men with low T had earlier AR (5.28 vs. 5.82, aOR: 0.73 [0.56-0.94]) and higher BMI (p < 0.001) from AR onward until age 46. Men with both early AR and low T had the highest BMI from AR onward. CONCLUSIONS: In men, maternal obesity and early weight gain associate with lower T levels at age 31, independently of adulthood abdominal obesity. Given the well-known health risks related to obesity, and the rising prevalence of maternal obesity, the results of the present study emphasize the importance of preventing obesity that may also affect the later reproductive health of the offspring.

Fear of childbirth after induced abortion in primiparous women: Population-based register study from Finland.

INTRODUCTION: Fear of childbirth (FOC) is a common obstetrical challenge that complicates about every 10th pregnancy. Background factors of FOC are diverse. We evaluated the association of induced abortion (IA) and FOC in subsequent pregnancy. MATERIAL AND METHODS: Population-based register study based on three Finnish national registers: the Register of Induced Abortions, the Medical Birth Register and the Hospital Discharge Register. The study cases were primigravid women undergoing an IA in 2000-2015 and subsequent pregnancy ending in live singleton birth up to 2017. Each case had three controls, matched by age and residential area, whose first pregnancy ended in a live birth. The main outcome was the incidence of FOC in the subsequent pregnancy. In a secondary analysis, we assessed other risk factors for FOC. RESULTS: The study cohort consisted of 21 455 women and 63 425 controls. Altogether, 4.2% of women had a diagnosis of FOC. The incidence was higher in women with a history of IA than in controls (5.6% vs 3.7%, P < 0.001). A history of IA was associated with higher odds for FOC: adjusted odds ratio [aOR] 1.20 with 95% confidence interval (CI) 1.11-1.30. In addition, a history of psychiatric diagnosis (aOR 3.48, 95% CI 3.15-3.83), high maternal age, 30-39 years old (aOR 1.55, 95% CI 1.43-1.67; P < 0.001) and ≥40 years old (aOR 3.00, 95% CI 2.37-3.77; P < 0.001) and smoking (aOR 1.20, 95% CI 1.11-1.31; P < 0.001) were associated with increased odds for FOC. Women living in densely populated or rural areas and those with lower socioeconomic class had lower odds for FOC. CONCLUSIONS: A history of IA is associated with increased odds for FOC in subsequent pregnancy. However, the associations of FOC with a history of psychiatric diagnosis and elevated maternal age (especially ≥40 years old) are more pronounced.

Whole-exome sequencing reveals candidate high-risk susceptibility genes for endometriosis.

BACKGROUND: Endometriosis is a common, chronic disease among fertile-aged women. Disease course may be highly invasive, requiring extensive surgery. The etiology of endometriosis remains elusive, though a high level of heritability is well established. Several low-penetrance predisposing loci have been identified, but high-risk susceptibility remains undetermined. Endometriosis is known to increase the risk of epithelial ovarian cancers, especially of endometrioid and clear cell types. Here, we have analyzed a Finnish family where four women have been diagnosed with surgically verified, severely symptomatic endometriosis and two of the patients also with high-grade serous carcinoma. RESULTS: Whole-exome sequencing revealed three rare candidate predisposing variants segregating with endometriosis. The variants were c.1238C>T, p.(Pro413Leu) in FGFR4, c.5065C>T, p.(Arg1689Trp) in NALCN, and c.2086G>A, p.(Val696Met) in NAV2. The only variant predicted deleterious by in silico tools was the one in FGFR4. Further screening of the variants in 92 Finnish endometriosis and in 19 endometriosis-ovarian cancer patients did not reveal additional carriers. Histopathology, positive p53 immunostaining, and genetic analysis supported the high-grade serous subtype of the two tumors in the family. CONCLUSIONS: Here, we provide FGFR4, NALCN, and NAV2 as novel high-risk candidate genes for familial endometriosis. Our results also support the association of endometriosis with high-grade serous carcinoma. Further studies are required to validate the findings and to reveal the exact pathogenesis mechanisms of endometriosis. Elucidating the genetic background of endometriosis defines the etiology of the disease and provides opportunities for expedited diagnostics and personalized treatments.

Sleep disturbances in women with early-onset menopausal transition: a population-based study.

OBJECTIVE: The aim of this study was to investigate sleep disturbances in 46-yr-old women and their association with early-onset menopausal transition. METHODS: The women of this cross-sectional birth cohort study were divided into climacteric (n = 359) and preclimacteric (n = 2,302) groups by their menopausal status, defined by follicle-stimulating hormone levels and menstrual history. Sleep disturbances were evaluated with Athens Insomnia Scale 5. We performed univariable and multivariable logistic regression models in which sleep parameters were dependent variables and climacteric status, hot flashes, smoking, and education level were independent variables. The use of hormone therapy was also evaluated in women suffering from sleeping disturbances. RESULTS: On the basis of the scale questions, climacteric women experienced significantly delayed sleep induction (12.2% vs 8.7%, P = 0.047), more problems with awakenings during the night (23.4% vs 14.6%, P < 0.001), earlier final awakening (13.8% vs 9.9%, P = 0.039), and more unsatisfying sleep quality (11.9% vs 7.9%, P = 0.023). Climacteric women who were experiencing hot flashes reported unsatisfactory sleep quality more frequently compared with climacteric women who did not experience hot flashes (17.0% vs 9.2%, P = 0.047). In the univariable and multivariable logistic regression models, being climacteric was independently associated with different impaired sleeping parameters. Most climacteric women who had a scale score of 4 or greater were not using hormone therapy, according to their medicine purchases over the past year. CONCLUSIONS: Being climacteric was associated with sleep disturbances in women in their mid-40s. However, this association seemed to be particularly driven by hot flashes. Most climacteric women with clinically significant sleeping disturbances were not using hormone therapy.

Association of climacterium with temporomandibular disorders at the age of 46 years - a cross-sectional study.

OBJECTIVE: Hormonal factors have been suggested to contribute to female dominance among subjects with temporomandibular disorders (TMD). Aim of the study was to examine the association of climacteric status with TMD amongst female participants in the Northern Finland Birth Cohort (NFBC) 1966 at 46 years of age. MATERIAL AND METHODS: Among female subjects in NFBC1966, climacteric status was determined based on menstrual anamnesis and measurement of blood follicle-stimulating hormone (FSH) levels. Women with FSH > 25 IU/L and amenorrhoea > 4 months were defined as climacteric (case group, n = 71); women not diagnosed as climacteric were defined as preclimacteric (control group, n = 656). Differences between cases and controls were evaluated on self-reported TMD pain, clinical TMD signs and TMD diagnoses using modified Diagnostic Criteria for TMD (DC/TMD) protocol. Crosstabulation and logistic regression models were used to analyse differences between cases and controls. RESULTS: Compared to preclimacteric women, climacteric women had significantly more often pain on palpation in temporomandibular joints (TMJs) (OR = 2.64, 95% CI 1.12-6.21, p= .026) and more crepitus in TMJs (OR = 2.92, 95% CI 1.13-7.56, p= .027). Degenerative joint disease diagnoses were more common in climacteric than preclimacteric women (OR = 2.27, 95% CI 1.05-4.91, p= .037). Differences were statistically significant after adjusting for confounding factors (body mass index (BMI), smoking, parity). No statistically significant differences in self-reported TMD pain were noted between groups. CONCLUSION: Among females at the age of 46 years, climacterium seems associated with TMD by increasing pain on palpation in TMJs, subjective symptoms, and clinical signs indicating degenerative changes in TMJs when using DC/TMD.

Climacteric status is associated with sexual dysfunction at the age of 46 years: a population-based study.

OBJECTIVE: Increasing age and menopausal transition increase the risk of sexual dysfunction. Sexual dysfunction is common in women experiencing menopause before the age of 40 years, whereas evidence on sexual function in women experiencing menopause in their mid-40s is scarce. We aimed to investigate sexual function in 46-year-old women in relation to their menopausal status. METHODS: This study cross-sectionally evaluated sexual function of women in a prospective population-based Northern Finland Birth Cohort 1966 (NFBC1966). A 46-year follow-up study of NFBC1966 included a broad questionnaire evaluating health, lifestyle, and life situation, as well as menstrual history and sexual function, and blood sampling analysis including follicle stimulating hormone and free androgen index (FAI). The participants were divided into two groups by their menopause status, defined by follicle-stimulating hormone and menstrual history. We performed logistic regression models in which parameters of sexual function were dependent factors and climacteric status, self-reported health, FAI, relationship status, smoking, and education level were independent variables. RESULTS: The study population included 2,661 women. In regression models, more advanced climacteric status was associated with higher frequency and difficulty level of low sexual desire and vaginal dryness (odds ratios with 95% confidence intervals: 2.80 [2.12-3.71], 3.22 [2.43-4.27], 3.83 [2.82-5.20], 3.75 [2.75-5.12], respectively), lower frequency of sexual thoughts (1.34 [1.02-1.75]), and higher frequency of problems with intercourse (2.35 [1.51-3.66]). Lower FAI and poorer health were associated with impaired sexual function. CONCLUSIONS: The current study suggests that women experiencing menopausal transition in their mid-40s are at risk of impaired sexual function.

Gravidity, parity and knee breadth at midlife: a population-based cohort study.

Gestation increases the biomechanical loading of lower extremities. Gestational loading may influence anthropometrics of articular surfaces in similar means as bone diaphyseal properties. This study aimed to investigate whether gravidity (i.e. number of pregnancies) and parity (i.e. number of deliveries) is associated with knee breadth among middle-aged women. The study sample comprised 815 women from the Northern Finland Birth Cohort 1966. The median parity count of our sample was 2 and the median gravidity count 3. At the age of 46, questionnaires were used to enquire gravidity and parity, and posteroanterior knee radiographs were used to obtain two knee breadth parameters (tibial plateau mediolateral breadth (TPML) and femoral condylar mediolateral breadth (FCML)) as representatives of articular size. The associations of gravidity and parity with knee breadth were analyzed using general linear models with adjustments for height, weight, leisure-time physical activity, smoking, and education years. Individuals with osteoarthritic changes were excluded from our sample. The mean TPML in our sample was 70.3 mm and the mean FCML 71.6 mm respectively. In the fully adjusted models, gravidity and parity showed positive associations with knee breadth. Each pregnancy was associated with 0.11-0.14% larger knee breath (p < 0.05), and each delivery accounted for an increase of 0.20% in knee breadth (p < 0.01). Between-group comparisons showed that multiparous women had 0.68-1.01% larger knee breath than nulli- and primiparous women (p < 0.05). Pregnancies and deliveries seem to increase the mediolateral breadth of the knee. This increase is potentially associated with increased biomechanical loadings during gestation.

Is climacterium by the mid-40s associated with thyroid dysfunction or autoimmunity? A population-based study.

OBJECTIVE: We investigated whether more advanced climacteric stage in the mid-40s is associated with thyroid autoimmunity and dysfunction. METHODS: This cross-sectional cohort study included 2,569 46-year-old women. Thyroid hormone, thyroid peroxidase antibodies, and follicle-stimulating hormone levels were determined. Using menstrual history and follicle-stimulating hormone levels, the participants were divided into climacteric (n = 340) and preclimacteric (n = 2,229) groups. Women diagnosed with premature ovarian insufficiency (menopause by 40 y of age) were excluded. The use of thyroid medication was evaluated from the medication reimbursement register. The prevalence of thyroid medication use, laboratory-based thyroid dysfunction, and thyroid peroxidase antibody positivity was compared between the two groups. The association between climacteric status and thyroid disorders was investigated using a logistic regression model including smoking and thyroid antibody status. RESULTS: At 46 years old, climacteric women used thyroid medication more often than preclimacteric women (9.1% vs 6.1%; P = 0.04). There was no difference in the prevalence of subclinical or clinical hypothyroidism and hyperthyroidism in nonmedicated participants (5.5% vs 5.0%; P = 0.7) or thyroid peroxidase antibody positivity (14.0% vs 15.0%, P = 0.7). In the regression model, being climacteric (OR = 1.6; 95% CI 1.1-2.3; P = 0.02) and antibody positivity (OR 4.9; 95% CI 3.6-6.6; P < 0.001) were associated with a higher prevalence of thyroid dysfunction. CONCLUSIONS: More advanced climacteric stage in the mid-40s was slightly associated with thyroid dysfunction but not thyroid autoimmunity.

Video Summary:http://links.lww.com/MENO/A771 .

Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study.

OBJECTIVE: To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties. METHODS: A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users. RESULTS: Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly. CONCLUSIONS: Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women.

Video Summary:http://links.lww.com/MENO/A648.

Vitamin D Levels in Women with Polycystic Ovary Syndrome: A Population-Based Study.

BACKGROUND: Conflicting evidence supports a role for vitamin D in women with reproductive disorders such as polycystic ovary syndrome (PCOS) but studies on large, unselected populations have been lacking. METHODS: We conducted a general population-based study from the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Serum 25-hydroksyvitamin D (25(OH)D) levels were evaluated in women with self-reported PCOS (n = 280) versus non-symptomatic controls (n = 1573) at the age of 31 with wide range of endocrine and metabolic confounders. RESULTS: The levels of 25(OH)D were similar among women with and without self-reported PCOS (50.35 vs. 48.30 nmol/L, p = 0.051). Women with self-reported PCOS presented with a higher body mass index (BMI), increased insulin resistance, and low-grade inflammation and testosterone levels compared to controls. The adjusted linear regression model showed a positive association between total 25(OH)D levels in self-reported PCOS (ß = 2.46, 95% confidence interval (CI) 0.84 to 4.08, p = 0.003). The result remained after adjustment for BMI, testosterone, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hs-CRP) levels. CONCLUSION: In this population-based setting, PCOS was associated with higher vitamin D levels when adjusting for confounding factors, without distinct beneficial effects on metabolic derangements.

Diagnostics of endometriosis by using magnetic resonance imaging.

Endometriosis affects about 2 to 10% of women in fertile age, It causes pain and infertility. In the ovaries, endometrios causes endometriomas. The disease may spread into the abdominal cavity and even result in ileus. Deep endometriomas are located under the peritoneal surface, typically behind the uterus and in the region of uterosacral ligaments. History, clinical examination and transvaginal ultrasound scanning usually lead to the diagnosis. Magnetic resonance imaging is in particular utilized prior to surgery. It provides a comprehensive view of endometriosis lesions in the pelvis, including deep foci.

[Adenomyosis - diagnostic and therapeutic challenge]. / Kohdun adenomyoosi - diagnostinen ja hoidollinen haste.

In adenomyosis, endometrial glandular and stromal cells grow inside the myometrium, and form localized or diffusely expanding islets. Smooth muscle cells of the uterus surrounding the adenomyosis colonies become hypertrophic, which may lead to abnormal contractions of the uterine wall. Adenomyosis is an estrogen-dependent disease with abnormal uterine bleeding and dysmenorrhea as typical symptoms. The disease may even be asymptomate. The diagnosis is made by histologically or ultrasonic or MRI imaging. Adenomyosis can be treated with hormonal medications. Fertility-sparing radiologic and surgical techniques are also available.

Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure.

BACKGROUND: Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). METHODS: This study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89). RESULTS: MMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies. CONCLUSIONS: Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Immediate complications after medical compared with surgical termination of pregnancy.

OBJECTIVE: To estimate the immediate adverse events and safety of medical compared with surgical abortion using high-quality registry data. METHODS: All women in Finland undergoing induced abortion from 2000-2006 with a gestational duration of 63 days or less (n=42,619) were followed up until 42 days postabortion using national health registries. The incidence and risk factors of adverse events after medical (n=22,368) and surgical (n=20,251) abortion were compared. Univariable and multivariable association models were used to analyze the risk of the three main complications (hemorrhage, infection, and incomplete abortion) and surgical (re)evacuation. RESULTS: The overall incidence of adverse events was fourfold higher in the medical compared with surgical abortion cohort (20.0% compared with 5.6%, P<.001). Hemorrhage (15.6% compared with 2.1%, P<.001) and incomplete abortion (6.7% compared with 1.6%, P<.001) were more common after medical abortion. The rate of surgical (re)evacuation was 5.9% after medical abortion and 1.8% after surgical abortion (P<.001). Although rare, injuries requiring operative treatment or operative complications occurred more often with surgical termination of pregnancy (0.6% compared with 0.03%, P<.001). No differences were noted in the incidence of infections (1.7% compared with 1.7%, P=.85), thromboembolic disease, psychiatric morbidity, or death. CONCLUSION: Both methods of abortion are generally safe, but medical termination is associated with a higher incidence of adverse events. These observations are relevant when counseling women seeking early abortion. LEVEL OF EVIDENCE: II.