Akter N, Kulinskaya E, Steel N, Bakbergenuly I. The effect of hormone replacement therapy on the survival of UK women: a retrospective cohort study 1984-2017. BJOG. 2021 Nov 12. doi: 10.1111/1471-0528.17008.
Objective
To estimate the effect of estrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46-65 at first prescription.
Design
- This was a matched cohort study of 105,199 HRT users (cases) and 224, 643 non-users (controls) matched on age and general practice extracted from the electronic primary care records from The Health Improvement Network (THIN) database, UK (1984-2017).
- Authors performed Weibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status. Main outcome measure was all-cause mortality.
Main findings
- A total of 21 751 women died over an average of 13.5 years follow-up per participant, of whom 6329 were users and 15 422 non-users.
- The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95% CI 0.88-0.94), and in estrogen-only users was 0.99 (0.93-1.07), compared with non-users.
- Age-specific adjusted HRs for participants aged 46-50, 51-55, 56-60 and 61-65 years at first treatment were 0.98 (0.92-1.04), 0.87 (0.82-0.92), 0.88 (0.82-0.93) and 0.92 (0.85-0.98) for combined HRT users compared with non-users, and 1.01 (0.84-1.21), 1.03 (0.89-1.18), 0.98 (0.86-1.12) and 0.93 (0.81-1.07) for estrogen-only users, respectively.
Take-home message
Combined HRT was associated with a 9% lower risk of all-cause mortality and estrogen-only formulation was not associated with any significant changes.
https://pubmed.ncbi.nlm.nih.gov/34773357/
Lee HR, Shin J, Han K, Chang J, Jeong SM, Chon SJ, Choi SJ, Shin DW. Obesity and Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study. J Clin Med. 2021;10(21):5189.
Background
Although both obesity and menopause are associated with increased risk of diabetes mellitus (DM), the association between obesity and DM according to menopausal status remains uncertain.
Objective
To examine the relationship between obesity and incidence of diabetes mellitus (DM) in premenopausal and postmenopausal women.
Design
- A total of 926,196 premenopausal and 1,193,881 postmenopausal women who underwent health examinations from 2009 to 2014 were identified using the database of the Korean National Health Insurance Service.
- Authors compared the incidence and risk of DM according to body mass index (BMI) and waist circumference (WC) in the two groups of women.
- Cox proportional hazards analyses were performed to evaluate the association between the presence of obesity and risk of DM according to menopausal state.
Main findings
- During the 7.8-year follow-up period, 37,736 (4.1%) premenopausal women and 121,102 (10.1%) postmenopausal women were diagnosed with DM.
- Compared to the reference group (BMI 18.5-23), a stronger association between obesity and risk of DM was observed in both pre- and postmenopausal women: multivariable-adjusted hazard ratios and 95% confidence intervals for BMI subgroups <18.5, 23-25, 25-30, and >30 were 0.62 (0.54, 0.70), 1.91 (1.85, 1.97), 3.38 (3.28, 3.47), and 6.25 (6.02, 6.48), respectively (p trend < 0.001) in premenopausal women and 0.87 (0.82, 0.92), 1.44 (1.41, 1.46), 2.00 (1.97, 2.03), and 2.96 (2.89, 3.02) in postmenopausal women (p trend < 0.001, p-interaction < 0.001).
- A similar trend was observed for WC. Subgroup analyses of women aged 45 to 55 also showed a stronger association with DM in premenopausal than in postmenopausal women.
Take-home messages
- The association between obesity and DM was stronger in premenopausal women than in postmenopausal women.
- As estrogens are synthesized in adipose tissue by aromatization of androgens after menopause, increased estrogen levels in obese postmenopausal might have a protective effect against DM.
https://pubmed.ncbi.nlm.nih.gov/34768709/
Salas R, Tijerina A, Cardona M, Bouzas C, Ramirez E, Martínez G, Garza A, Pastor R, Tur JA. Association between Bone Mineral Density and Metabolic Syndrome among Reproductive, Menopausal Transition, and Postmenopausal Women. J Clin Med. 2021;10(21):4819.
Background
The menopausal transition stage brings physiological changes associated with the development of metabolic syndrome (MetS), which can affect bone mineral density (BMD), and may be more evident in the postmenopausal stage.
Objective
To assess the association between low BMD and MetS and its components among reproductive/menopausal transition and postmenopausal women in the northeast region of Mexico.
Design
- This was a descriptive cross-sectional study carried out (2015-2016) in 40-60-year-old women (n = 376) who were residents in the metropolitan area of Monterrey, in Nuevo Leon State, Mexico.
- Anthropometric measurements, blood pressure, a dual-energy X-ray absorptiometry (DXA) evaluation of BMD of two anatomical sites (lumbar spine and dual femur), and a biochemical analysis were obtained.
Main findings
- The prevalence of MetS was 57.2%.
- In participants without MetS, the prevalence of osteopenia was 27.3% in the lumbar spine and 18.6% in the dual femur, while in participants with MetS, the prevalence of osteopenia was 35.8% in the lumbar spine and 14.4% in the dual femur.
- Osteoporosis in participants without MetS was present in 6.8% in the lumbar spine and in 1.8% in the dual femur, while in women with MetS, its prevalence was 4.7% in the lumbar spine and 0.5% in the dual femur.
- An association between low BMD at the lumbar spine and dual femur and components of MetS diseases was identified in Mexican women as follows: waist circumference ≥ 88 cm showed an increase risk for low BMD at femoral site in both reproductive/menopausal transition (OR 7.638; 95% CI: 1.607-36.298; p = 0.011) and postmenopausal women (OR 2.600; 95% CI: 1.023-6.609; p = 0.045); HDL < 50 mg/dL was associated with low BMD in both the femur (OR 3.639; 95% CI: 1.039-12.743; p = 0.043) and lumbar spine (OR 2.654; 95% CI: 1.092-6.447; p = 0.031); hypertension in postmenopausal women increased the risk for low BMD in the femur (OR 2.634; 95% CI: 1.150-6.035; p = 0.022).
Take-home messages
- The components of the MetS were associated with low BMD, thus indicating that MetS increases the risk for developing osteopenia or osteoporosis.
- Furthermore, age was found to be an independent risk factor for low BMD.
https://pubmed.ncbi.nlm.nih.gov/34768336/
Rocca WA, Lohse CM, Smith CY, Fields JA, Machulda MM, Mielke MM. Association of Premenopausal Bilateral Oophorectomy With Cognitive Performance and Risk of Mild Cognitive Impairment. JAMA Netw Open. 2021;4(11):e2131448.
Background
The associations of bilateral oophorectomy among premenopausal women, age at oophorectomy, and use of estrogen therapy after oophorectomy with cognitive performance later in life remain controversial.
Objective
To investigate whether women who underwent premenopausal bilateral oophorectomy were at increased risk of mild cognitive impairment (MCI) and experienced decreased global or domain-specific cognitive performance.
Design
- This was a case-control study and cross-sectional study made possible by combining data from the Mayo Clinic Study of Aging (MCSA) and the Rochester Epidemiology Project (REP) medical record-linkage system.
- The studies were conducted among a population-based sample in Olmsted County, Minnesota, consisting of 2,732 women aged 50 to 89 years who participated in the MCSA study from 2004 to 2019 and underwent a clinical evaluation and comprehensive cognitive testing.
- Data were analyzed from January to May 2021.
- Exposures were medical record documentation of bilateral oophorectomy abstracted from a medical record-linkage system (ie, REP) and main outcomes and measures: Odds of MCI and global or domain-specific z scores on cognitive tests were measured at the first MCSA visit. The median (IQR) lag time between bilateral oophorectomy performed before menopause and before age 50 years and cognitive evaluation was 30 (22-38) years.
Main findings
- Among 2,732 women aged 50 to 89 years (median [IQR] age at evaluation, 74 [66-81] years) who participated in the MCSA, the case-control study included 283 women with MCI (10.4%) and 2449 women without cognitive impairment (89.6%).
- Bilateral oophorectomy before menopause and before age 46 years was associated with clinically diagnosed MCI (adjusted odds ratio [aOR], 2.21; 95% CI, 1.41-3.45; P < .001) compared with no bilateral oophorectomy.
- The presence of an association with MCI varied by surgical indication, with an association among 259 women with bilateral oophorectomy before menopause and before age 50 years for the indication of benign ovarian condition (aOR, 2.43; 95% CI, 1.36-4.33; P = .003) but not for cancer or no ovarian condition.
- The presence of an association did not vary by estrogen therapy after bilateral oophorectomy, with associations among women aged less than 46 years with estrogen therapy (aOR, 2.56; 95% CI, 1.24-5.31; P = .01) and without estrogen therapy (aOR, 2.05; 95% CI, 1.18-3.52; P = .01). The cross-sectional study included 625 women with a history of bilateral oophorectomy (median [IQR] age, 75 [70-82] years) and 2107 women without a history of bilateral oophorectomy (median [IQR] age, 73 [65-80] years).
- Premenopausal bilateral oophorectomy was performed before age 46 years among 161 women and was associated with decreased global cognition z score (β, -0.17; 95% CI, -0.32 to -0.03; P = .02), attention and executive domain z score (β, -0.21; 95% CI, -0.36 to -0.05; P = .009), and Short Test of Mental Status score (β, -0.51; 95% CI, -0.95 to -0.08; P = .02) compared with no bilateral oophorectomy.
Take-home message
Women who underwent bilateral oophorectomy before menopause had increased odds of MCI and poorer performance on cognitive tests approximately 30 years later compared with women who did not undergo bilateral oophorectomy.
https://pubmed.ncbi.nlm.nih.gov/34762113/
Khandkar C, Vaidya K, Karimi Galougahi K, Patel S. Low bone mineral density and coronary artery disease: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2021 Oct 23;37:100891. doi: 10.1016/j.ijcha.2021.100891.
Background
- Coronary artery disease (CAD) and osteoporosis both cause significant morbidity and mortality.
- Recent interest in inflammation and the bone-vascular axis suggests a mechanistic link between the two conditions.
Objective
To examine the potential association between low bone mineral density (BMD) and CAD in adults.
Design
- This was a review and meta-analysis.
- Two authors searched for studies that examined the association between low BMD and CAD.
- Risk of bias assessment was conducted using the modified Newcastle Ottawa score.
- Ten studies were selected from the 2258 unique records identified.
Main findings
- Pooled analysis showed a significant association between low BMD and CAD (OR 1.65, 95%CI 1.37-2.39, p < 0.01).
- Subgroup analysis investigating males and females separately was not significant.
- The subgroup analyses looking for any differences across geographic locations and differences between coronary imaging modalities were also negative.
- Studies with adjusted ORs (n = 4) were also pooled (OR 3.01, 95%CI 0.91-9.99, p = 0.07).
Take-home messages
- Low BMD is associated with CAD; however, it is unclear whether this result is confounded by common risk factors given the heterogeneity between study populations and methodologies.
- Further large-scale epidemiological studies are required.
https://pubmed.ncbi.nlm.nih.gov/34746361/
Sharma A, Ogunmoroti O, Fashanu OE, Zhao D, Ouyang P, Budoff MJ, Thomas IC, Michos ED. Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2022;341:71-79.
Background
- Sex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD).
- High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women.
Objective
To examine the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants.
Design
- Authors studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels.
- ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years.
- Investigators used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately.
Main findings
- The mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively.
- In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only.
- In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors.
Take-home messages
- In this diverse cohort free of CVD, authors found some associations of SH with ECC measures.
- In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors.
- SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.
https://pubmed.ncbi.nlm.nih.gov/34785061/
Tanmahasamut P, Rattanachaiyanont M, Techatraisak K, Indhavivadhana S, Wongwananuruk T, Chantrapanichkul P. Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis. Climacteric. 2021 Nov 16:1-7. doi: 10.1080/13697137.2021.1998434.
Objective
To investigate the relationship between menopausal hormone therapy (MHT) and endometriosis recurrence in women who underwent hysterectomy with bilateral salpingo-oophorectomy to treat endometriosis.
Design
- This was a retrospective cohort study that included 330 women who underwent definitive surgery to treat endometriosis during 1996-2012.
- Follow-up data until December 2018 were analyzed.
- Patients were grouped as MHT non-users (non-MHT, n = 43), estrogen-only therapy (ET, n = 230), estrogen-progestogen therapy (EPT, n = 39) and tibolone (n = 18).
Main findings
- The mean age at surgery was 41.5 ± 5.3 years.
- The overall median follow-up duration was 6.0 years (interquartile range [IQR]: 3.0-10.4), and the median duration of MHT use was 66.0 months (IQR: 36.0-116.3).
- The overall recurrence rate was 3.0% (95% confidence interval: 1.5-5.5) and there was no significant difference in recurrence among the study groups.
- Disease recurrence resolved after MHT discontinuation, or change in MHT type and/or dose.
Take-home messages
- No significant association between MHT use and endometriosis recurrence was found in this study.
- The endometriosis recurrence rate was non-significantly different between ET and EPT.
- Recurrent endometriosis can be successfully treated without invasive measures.
- No study patients had malignant transformation after a median follow-up of 6 years.
- Findings suggest that any of the three evaluated MHT regimens can be used in surgically menopausal Thai women with underlying endometriosis.
https://pubmed.ncbi.nlm.nih.gov/34783284/
Pourhassan M, Buehring B, Stervbo U, Rahmann S, Mölder F, Rütten S, Trampisch U, Babel N, Westhoff TH, Wirth R. Osteosarcopenia, an Asymmetrical Overlap of Two Connected Syndromes: Data from the OsteoSys Study. Nutrients. 2021;13(11):3786.
Background
Osteoporosis and sarcopenia are two chronic conditions, which widely affect older people and share common risk factors.
Objective
To investigate the prevalence of low bone mineral density (BMD) and sarcopenia, including the overlap of both conditions (osteosarcopenia).
Design
- This was a prospective observational multicenter study that included 572 older hospitalized patients (mean age 75.1 ± 10.8 years, 78% women) with known or suspected osteoporosis.
- Sarcopenia was assessed according to the revised definition of the European Working Group on Sarcopenia in Older People (EWGSOP2).
- Low BMD was defined according to the World Health Organization (WHO) recommendations as a T-score < -1.0 and osteosarcopenia was diagnosed when both low BMD and sarcopenia were present.
Main findings
- Low BMD was prevalent in 76% and the prevalence of sarcopenia was 9%, with 90% of the sarcopenic patients showing the overlap of osteosarcopenia (8% of the entire population).
- Conversely, only few patients with low BMD demonstrated sarcopenia (11%).
- Osteosarcopenic patients were older and frailer and had lower BMI, fat, and muscle mass, handgrip strength, and T-score compared to non-osteosarcopenic patients.
- Osteosarcopenia is extremely common in sarcopenic subjects.
- Considering the increased risk of falls in patients with sarcopenia, they should always be evaluated for osteoporosis.
https://pubmed.ncbi.nlm.nih.gov/34836043/
Dziedzic EA, Smyk W, Sowińska I, Dąbrowski M, Jankowski P. Serum Level of Vitamin D Is Associated with Severity of Coronary Atherosclerosis in Postmenopausal Women. Biology (Basel). 2021;10(11):1139.
Background
Postmenopausal women experience rapid progression of coronary artery disease. Vitamin D deficiency appears to be a modifiable risk factor for cardiovascular diseases.
Objective
To analyze the impact of 25-hydroxyvitamin D3 (25(OH)D) level on the severity of coronary atherosclerosis and its potential cardioprotective effect in postmenopausal women.
Design
- The was a prospective study that recruited 351 women in postmenopausal age undergoing coronary angiography.
- The severity of coronary atherosclerosis was assessed using the Coronary Artery Surgery Study Score (CASSS). A level of 25(OH)D was measured with electrochemiluminescence.
Main findings
- Women with more severe coronary atherosclerosis have significantly lower 25(OH)D serum level (p = 0.0001).
- Vitamin D (β = -0.02; p = 0.016), hypertension (β = 0.44; p = 0.025), age (β = 0.02; p = 0.003), and history of MI (β = 0.63; p < 0.0001), were shown as CASSS determinants.
- Age, hyperlipidemia, and history of MI were found to determine the level of vitamin D (all p < 0.05).
- Women with a three-vessel disease hospitalized due to ACS, with a history of MI, hyperlipidemia and hypertension presented the lowest vitamin D level.
Take-home message
Lower serum 25(OH)D in postmenopausal women is associated with more significant stenosis in the coronary arteries; therefore, low vitamin D levels can be considered as a potential risk factor for coronary artery disease.
https://pubmed.ncbi.nlm.nih.gov/34827132/
Wang L, Zhu L, Yao Y, Ren Y, Zhang H. Role of hormone replacement therapy in relieving oral dryness symptoms in postmenopausal women: a case control study. BMC Oral Health. 2021;21(1):615.
Objective
To evaluate the efficacy of hormone replacement therapy in relieving oral symptoms in postmenopausal women presenting with genitourinary symptoms along with oral dryness.
Design
- This was a case-control study conducted after selecting 60 postmenopausal women.
- Oral dryness status of all the patients was evaluated with the help of questionnaire related to oral dryness.
- These subjects were divided into case group and control group on the basis of response to questionnaire of oral dryness.
- Unstimulated saliva samples were obtained and analyzed for estimation of salivary estradiol levels by enzyme linked immune sorbent assay technique.
- After analyzing the result of salivary estradiol levels, case group was subjected to hormone replacement therapy (HRT).
- The patients were followed up for their response towards oral dryness as well as salivary estradiol levels after the therapy.
Main findings
- The mean salivary estradiol level before HRT was significantly more among control group as compared to case group (p value < 0.001).
- Most of the patients complained of dry mouth (26 out of 30); reduced amount of saliva in the mouth (25 out of 30); dry mouth at night (28 out of 30); dry mouth during the day (25 out of 30) before HRT.
- These complains were significantly reduced after the therapy.
- The mean salivary estradiol in the case group levels increased significantly after HRT (p value < 0.001).
Take-home messages
- The salivary estradiol levels were reduced in postmenopausal women with the complain of xerostomia as compared to those without the complain of xerostomia.
- Further these levels can be recovered with the help of hormone replacement therapy.
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