A systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases

Kim, Ji Eun; Chang, Jae Hyuck; Jeong, Min Ji; Choi, Jaesung; Park, Joo Yong; Baek, Chaewon; Shin, Aesun; Park, Sang Min; Kang, Daehee; Choi, Ji Yeob

doi:10.1038/s41598-020-77534-9

Cited by 44 publications

(44 citation statements)

References 49 publications

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“…The previous study compared CEE to esterified estrogen and found that duration of CEE use is associated with the risk of stroke 29 . In addition, the previous meta-analysis showed that HT duration of 5 years or more was associated with an increased risk of IS 25 . The mean duration of using HT was 2.1-3.9 years.…”

Section: Discussionmentioning

confidence: 99%

“…A recent comprehensive review and meta-analysis regarding the effects of HT on cardiovascular disease, including stroke, showed that HT increased the risk of VTE (randomized controlled trials, summary estimate (SE), 1.70; 95% CI 1.33–2.16; observational studies, SE, 1.32; 95% CI 1.13–1.54) and stroke (SE, 1.14; 95% CI 1.04–1.25) 25 . As regards underlying disease, HT in patients with underlying diseases was associated with a higher risk of stroke (SE, 1.14; 95% CI 1.04–1.26).…”

Section: Discussionmentioning

confidence: 99%

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Conjugated equine estrogen used in postmenopausal women associated with a higher risk of stroke than estradiol

Chang

Wang

Ding

2021

Sci Rep

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This study aimed to evaluate the risk of ischemic stroke (IS) in hormone therapy (HT) with oral conjugated equine estrogen (CEE) and estradiol (E2) in postmenopausal women in Taiwan. A retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women, aged 40–65 years, who received HT with E2 and CEE orally were enrolled. The primary outcome was IS. Propensity score matching with menopausal age and comorbidities was used. Cox proportional hazard regression models were used to calculate the incidence and hazard ratios (HRs) for IS. The mean menopausal ages of the E2 and CEE groups were 50.31 ± 4.99 and 50.45 ± 5.31 years, respectively. After adjusting for age and comorbidities, the incidence of IS was 1.17-fold higher in the women treated with CEE than in those treated with E2 (4.24 vs. 3.61/1000 person-years), with an adjusted HR (aHR) of 1.23 (95% confidence interval [CI] 1.05–1.44). Moreover, HT with CEE initiated within 5 years of menopause had a higher HR than E2 (aHR = 1.20; 95% CI 1.02–1.42). In conclusion, HT with oral CEE might be associated with a higher risk of IS than E2 in postmenopausal Taiwanese women. The use of HT with CEE should be cautioned with the risk of IS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Conjugated equine estrogen used in postmenopausal women associated with a higher risk of stroke than estradiol

Chang

Wang

Ding

2021

Sci Rep

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“…A recent metanalysis suggested an increased risk of stroke in older women, related to underlying disease and timing of initiation of hormonal replacement [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In individuals over 80 years old, the pathogenic puzzle is uncertain, and data is scarce. Some authors have suggested new modulators for atherogenesis as cellular senescence, syndrome of frailty, sarcopenia [23,28]. Sarcopenia is a relevant component of senescence and frailty syndrome and may increase the atherogenic process due to the replacement of muscle mass by adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

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Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Rosa

Soares

Rodrigues

et al. 2021

Clin Diabetes Endocrinol

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Background Hypopituitarism in the elderly population is an underdiagnosed condition and may increase comorbidities related to glucose metabolism, dyslipidemia, and cardiovascular risk factors. Optimization of hormone replacement that considers alterations in clearance rates of hormones, interaction with other medications, and evaluation of the risk-benefit ratio of treatment is a big challenge for clinical practice. Objectives This study aimed to evaluate classic cardiovascular risk factors in hypopituitary septuagenarians and octagenarians by diagnosis and after long-term hormone replacement. Methods This is a retrospective observational study, with patients recruited and selected from a registry in a tertiary medical center. We included patients aged 70–99 years with hypopituitarism, evaluated hormonal and biochemical parameters, and cardiovascular risk scores were calculated by diagnosis and compared after long-term follow-up. All patients gave informed consent. Patient data were compared to a sex and age-matched control group, with long-term geriatric follow-up, without endocrine diseases. Results Thirty-five patients were included, 16 patients aged 70–75 years (72.61), 12 patients 76–80 years (72.28), 7 patients 81–99 years (89.28). Pituitary macroadenomas were the main cause of hypopituitarism, mean maximal diameter 3.4 cm (2.9–4.3), and invasive craniopharyngiomas. At the moment of diagnosis, most patients were overweight, and abdominal adiposity was observed in 76.9% of women and 36.4% of men, primarily in octagenarians and nonagenarians. Comorbidities were frequent; 85.7% presented hypertension, 37.1% diabetes, 53.1% low HDL, 51.5% hypertriglyceridemia. Most patients presented more than two combined pituitary deficiencies; hypogonadism in 88.6%, central hypothyroidism in 82.9%, GH deficiency in 65.7%, and adrenal insufficiency in 25.7%. Analysis of cardiovascular risk prediction in the total cohort showed that 57.1% of patients presented a reduction in the General Cardiovascular Disease (CVD) Risk Prediction Score and 45.7% in atherosclerotic CVD risk estimated by ACC/AHA 2013 Pooled Cohort Equation, despite being submitted to conventional hormone replacement, during the mean follow-up of 14.5 years. This reduction was not observed in the control group. Discussion and conclusion In this study, aged hypopituitary patients presented a reduction in estimated general CVD risk during long-term follow-up, despite replacement with corticosteroids, levothyroxine, or gonadal steroids. Early diagnosis and treatment of hypopituitarism in the elderly remain challenging. Larger studies should be performed to assess the risk-benefit ratio of hormone replacement on the metabolic profile in septuagenarian and octogenarian patients.

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Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy

Davis,

Weller,

Porterfield

et al. 2023

JAMA Netw Open

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ImportanceAlthough hormone therapy (HT) in perimenopausal women is associated with increased risk for venous thromboembolism (VTE), it is unclear to what extent statins may mitigate this HT-associated risk.ObjectiveTo estimate VTE risk in women aged 50 to 64 years taking HT with or without statins.Design, Setting, and ParticipantsThis nested case-control study analyzed data from a commercially insured claims database in the US. Eligible participants included women aged 50 to 64 years with at least 1 year of continuous enrollment between 2008 and 2019. Data analysis occurred from January 2022 to August 2023.ExposureFilled prescriptions for estrogens, progestogens, and statins were recorded in the 12 months prior to index. Recent HT was defined as any estrogen or progestogen exposure within 60 days before the index date. Current statin exposure was defined as 90 or more days of continuous exposure prior to and including the index date. Statin intensity was defined by the statin exposure 30 days prior to index.Main Outcomes and MeasuresCases were identified with VTE diagnoses (diagnostic codes) preceded by at least 12 months without VTE and followed within 30 days by anticoagulation, an inferior vena cava filter placement, or death. Controls were matched to cases (10:1) on date and age. Conditional logistic regression models estimated risk for HT and statin exposures with odds ratios (OR), adjusted for comorbidities. Conditional logistic regression models were used to estimate VTE risk for HT and statin exposures with odds ratios (ORs), adjusted for comorbidities. Intensity of statin therapy was measured as a subgroup analysis.ResultsThe total sample of 223 949 individuals (mean [SD] age, 57.5 [4.4] years) included 20 359 cases and 203 590 matched controls. Of the entire sample, 19 558 individuals (8.73%) had recent HT exposure and 36 238 individuals (16.18%) had current statin exposure. In adjusted models, individuals with any recent HT exposure had greater odds of VTE compared with those with no recent HT exposure (OR, 1.51; 95% CI, 1.43-1.60). Individuals receiving current statin therapy had lower odds of VTE compared with those with no current statin exposure (OR, 0.88; 95% CI, 0.84-0.93). When compared with those not recently taking HT or statins, the odds of VTE were greater for those taking HT without statins (OR, 1.53; 95% CI, 1.44-1.63) and for those taking HT with statins (OR, 1.25; 95% CI, 1.10-1.43), but were lower for those taking statins without HT (OR, 0.89; 95% CI, 0.85-0.94). Individuals taking HT with statin therapy had 18% lower odds of VTE than those taking HT without statins (OR, 0.82; 95% CI, 0.71-0.94) and there was greater risk reduction with higher intensity statins.Conclusions and RelevanceIn this case-control study, statin therapy was associated with reduced risk of VTE in women taking HT, with greater risk reduction with high-intensity statins. These findings suggest that statins may reduce risk of VTE in women exposed to HT and that HT may not be contraindicated in women taking statins.

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A systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases

Cited by 44 publications

References 49 publications

Conjugated equine estrogen used in postmenopausal women associated with a higher risk of stroke than estradiol

Conjugated equine estrogen used in postmenopausal women associated with a higher risk of stroke than estradiol

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy

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