Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women

Gartlehner, Gerald; Patel, Sheila V.; Feltner, Cynthia; Weber, Rachel Palmieri; Long, Rachel de; Mullican, Kelly; Boland, Erin; Lux, Linda J; Viswanathan, Meera

doi:10.1001/jama.2017.16952

Cited by 125 publications

(68 citation statements)

References 80 publications

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“…A meta-analysis of existing trials, 7 taken largely from the Women’s Health Initiative study, provided estimates only for the specific treatments of conjugated equine oestrogen with and without medroxyprogesterone. 6 In contrast to our estimates of a slightly increased risk for long term users of conjugated equine oestrogen (average duration for recent exposure of 5.6 years, odds ratio 1.07, 95% confidence interval 1.01 to 1.12), the meta-analysis found no difference in risk of breast cancer (relative risk 0.79, 95% confidence interval 0.61 to 1.02) after a mean duration of 7.2 years. The observed relative risk for the combined conjugated equine oestrogen with medroxyprogesterone therapy after a mean duration of 5.6 years (1.27, 1.03 to 1.56) was similar to our findings for recent exposure, with an average duration of 3.7 years (odds ratio 1.35, 1.30 to 1.41).…”

Section: Discussioncontrasting

confidence: 96%

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

Vinogradova

Coupland

Hippisley‐Cox

2020

BMJ

147

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Objective To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). Design Two nested case-control studies. Setting UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. Participants 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 female controls. Main outcome measures Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. Results Overall, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 women years. Conclusion This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.

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Section: Discussioncontrasting

confidence: 96%

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

Vinogradova

Coupland

Hippisley‐Cox

2020

BMJ

147

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“…Despite HRT being an effective treatment option to manage symptoms [6], the abrupt halt of the Women’s Health Initiative in 2002 instilled confusion (and fear) surrounding the link between HRT use and risk of coronary heart disease events, stroke, and breast cancer [7–9]. Specifically, the use of HRT has declined from 44% of U.S. women using or having used HRT in 1988–1994 to 4.7% of women in 2010 [8,9]. As risk factors change over time, and overall usage guidelines updated, HRT prescription should be carefully evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Hormone replacement therapy (HRT) is the most effective treatment for VMS [6]; however, concerns surrounding its potential health risk still remain [7–9]. Conversely, non-pharmacologic, physician-recommended care often includes adopting a healthy lifestyle (e.g., healthier eating, increased physical activity) primarily to mitigate metabolic impairments and secondarily to curb menopausal symptoms [1,10].…”

Section: Introductionmentioning

confidence: 99%

A qualitative assessment of health behaviors and experiences during menopause: A cross-sectional, observational study

2018

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Objectives: A qualitative research study was performed to assess health and lifestyle behaviors of middle-age women during the menopause transition, as well as inform the development of future interventions designed to combat menopause symptoms and improve quality of life during and after menopause. Study Design: Data were collected from 1,611 women via a 21-item questionnaire distributed electronically. Only women who self-reported age ≥40 years and were either peri-menopausal or post-menopausal were included in the analyses Outcome Measures: Women responded to questions about their health behaviors and experiences during menopause, including use of hormone replacement therapy (HRT); symptom ratings; and use of diet/lifestyle, exercise, and holistic remedies to relieve menopause symptoms. Results: More than 80% of women were interested in a structured lifestyle program to alleviate menopause symptoms, with 72% of these women wanting targeted strategies for weight loss or weight maintenance. Insomnia and hot flashes were the most severe symptoms reported. Although HRT is a well-established treatment to relieve symptoms, more than 60% of women denied use of HRT citing that they ‘never considered HRT’ as a treatment option or ‘preferred to not take HRT’. Most women (65%) did not feel prepared for menopause. Conclusions: Women do not feel prepared for menopause and report interest in a structured lifestyle program containing weight loss and weight maintenance strategies to combat menopause symptoms.

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“…Postmenopausal osteoporosis is the most common type of primary osteoporosis, and, resulted from global aging, its incidence is increasing recently (Compston et al, 2019). PMOP leads to an increased risk of fractures and chronic pain, which reduces the quality of life for older women and increases the burden on society (Gartlehner et al, 2017). After menopause, estrogen withdrawal weakens its inhibitory effect on inflammatory cytokines, leading to the increase of inflammatory cytokines in the body, which further breaks the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption (Eastell et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

et al. 2020

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Postmenopausal osteoporosis (PMOP) is a metabolic bone disease characterized by decreased bone density and strength due to the imbalance between osteogenesis and osteoclastogenesis. Postmenopausal estrogen withdrawal increases proinflammatory cytokines and increases the serum level of Receptor activator of NF-kB ligand (RANKL)/Osteoprotegerin (OPG), which then leads to the overactivation of osteoclastogenesis. Tetrandrine, a bis-benzylisoquinoline alkaloid, has been widely used in the treatment of rheumatoid arthritis clinically in China. Here, we demonstrate that tetrandrine significantly prevented ovariectomy-induced bone loss and inhibited RANKL-induced osteoclastogenesis. In vivo, we found that intraperitoneal injection of tetrandrine (30 mg/kg) every other day markedly reduced bone loss in ovariectomized mice and the serum levels of TRAcp5b, TNF-a, IL-6, CTX-I, and RANKL/OPG were significantly decreased. In vitro, we found that tetrandrine significantly inhibited osteoclast differentiation in bone marrow monocytes (BMMs) and RAW264.7 cells according to the results of osteoclastogenesis-related gene expression, tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption assay. Mechanistically, tetrandrine inhibited RANKL-induced osteoclastogenesis by suppressing NF-kB, Ca2 + , PI3K/AKT, and MAPKs signaling pathways. Taken together, our findings suggest that tetrandrine suppresses osteoclastogenesis through modulation of multiple pathways and has potential value as a therapeutic agent for PMOP, especially for those suffering from RA and PMOP at the same time.

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Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women

Cited by 125 publications

References 80 publications

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

A qualitative assessment of health behaviors and experiences during menopause: A cross-sectional, observational study

Tetrandrine Prevents Bone Loss in Ovariectomized Mice by Inhibiting RANKL-Induced Osteoclastogenesis

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