postmenopause

Endometrial cancer accounts for 95% of uterine cancers, which are the fourth most common cancer in women in the US.1 Approximately 1 in 32 women in the US will develop endometrial cancer in their lifetimes. Eighty percent of endometrial cancer cases in the US are diagnosed in postmenopausal women, and the average age at diagnosis is 60 years. However, rates of endometrial cancer are increasing in both older and younger women in the US and worldwide.

A leading risk factor for endometrial cancer is obesity. Other common risk factors are diabetes and a personal or family history of inherited conditions such as Lynch syndrome (a genetic disorder that increases the risk of multiple types of cancer). Additional risk factors include use of estrogen without progesterone, tamoxifen (a medication to treat or prevent hormone receptor–positive breast cancer), and having never been pregnant. In contrast, combined oral contraceptives and progesterone therapy, including progesterone-releasing intrauterine devices, are associated with a decreased risk of endometrial cancer.

Nonhormonal Treatment of Menopausal Vasomotor Symptoms

Erin Blanchette — Wed, 07 May 2025 21:26:26 +0000

Date Added:

May 7, 2025

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

May 5, 2025

URL:

Nonhormonal Treatment of Menopausal Vasomotor Symptoms

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2025.0990

Keywords

Obstetrics and Gynecology

PMID (1):

40323611

MeSH

A concise evidence-based review of non-hormonal approaches to treatment of menopausal vasomotor symptoms. James W. Mold, MD, MPH

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Vasomotor symptoms are the most widely recognized menopause symptoms in Western nations, with at least 75% of women reporting hot flashes or night sweats during or after the menopause transition. Many women struggle to choose between treatments, given lack of data on direct comparisons of different treatments, concerns about short-term adverse effects and longer-term treatment risks, and confusion about complementary or alternative remedies with unclear evidence of benefit.

Author/s:

Alison J Huang, Stephanie Faubion, Deborah Grady

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement

Alex Haga — Mon, 24 Feb 2025 17:44:58 +0000

Date Added:

February 24, 2025

Journal/Publication:

JAMA

Publication Date:

January 14, 2025

Issue:

Volume:

333

Pages:

498-508

URL:

Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.27154

Keywords

MeSH

osteoporotic fractures

female

USPSTF recommendations regarding screening for osteoporosis in older women. James W. Mold, MD, MPH

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Importance Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death.

Objective The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture.

Population Adults 40 years or older without known osteoporosis or history of fragility fractures.

Evidence Assessment The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older has moderate net benefit. The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk has moderate net benefit. The USPSTF concludes that the evidence is insufficient and the balance of benefits and harms for screening for osteoporosis to prevent osteoporotic fractures in men cannot be determined.

Recommendation The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older. (B recommendation) The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years who are at increased risk for an osteoporotic fracture as estimated by clinical risk assessment. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men. (I statement)

Author/s:

US Preventive Services Task Force

Urinary tract infections after menopause

Alex Haga — Tue, 11 Feb 2025 23:25:58 +0000

Date Added:

February 11, 2025

Journal/Publication:

Canadian Medical Association Journal

Publication Date:

February 2, 2025

Issue:

Volume:

197

Pages:

E96

URL:

Urinary tract infections after menopause

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.241258

Keywords

urinary tract infections

UTIs

postmenopause

PMID (1):

39900362

MeSH

postmenopause

urinary tract infections

menopause

A concise review of the diagnosis and management of UTIs in post menopausal women. James W. Mold, MD, MPH

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No abstract is included with this article.

Author/s:

Erin A Brennand, Jayna Holroyd-Leduc

The Women’s Health Initiative Randomized Trials and Clinical Practice

Alex Haga — Mon, 13 May 2024 21:25:57 +0000

Date Added:

May 13, 2024

Journal/Publication:

JAMA

Publisher:

JAMA

Publication Date:

May 1, 2024

URL:

The Women’s Health Initiative Randomized Trials and Clinical Practice

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2024.6542

Keywords

PMID (1):

38691368

A summary review of the results of the Womens Health Initiative Study pertaining to HRT, Vit D/calcium supplementation, and low-fat diet in menopausal women. James W. Mold, MD, MPH

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Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years.

Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up.

Conclusions and relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Author/s:

Manson, J.E., Crandall, C.J., Rossouw, J.E.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women

Erin Blanchette — Mon, 06 May 2024 17:49:34 +0000

Date Added:

May 6, 2024

Journal/Publication:

Cochrane Database of Systematic Reviews

Publisher:

Wiley

Publication Date:

April 9, 2024

Issue:

Volume:

URL:

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD003376.pub4.

Keywords

Etidronic Acid

Osteoporotic Fractures

postmenopause

Wrist Fractures

bones

PMID (1):

38591743

MeSH

Etidronic Acid

osteoporotic fractures

postmenopause

Wrist Fractures

Bone and Bones

This updated Cochrane review found little evidence that etidronate makes a clinical significant difference in the rate of osteoporotic fractures in post-menopausal women. James W. Mold, MD, MPH

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Background: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high).

Objectives: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively.

Search methods: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023.

Selection criteria: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study.

Main results: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies.

Authors' conclusions: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Osteoporosis Screening in Younger Postmenopausal Women

Brian Desmarais — Sat, 11 Jan 2020 20:19:49 +0000

Date Added:

January 11, 2020

Journal/Publication:

Journal of the American Medical Association

Publication Date:

January 9, 2020

URL:

Osteoporosis Screening in Younger Postmenopausal Women

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi:10.1001/jama.2019.18343

Keywords

MeSH

osteoporotic fractures

This is a nice review of when to consider screening for osteoporosis in postmenopausal women younger than 65. James W. Mold, MD, MPH

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Osteoporotic fractures, especially hip fractures, are associated with mobility limitations, chronic disability, loss of independence, and reduced quality of life.

Several randomized trials have demonstrated the benefit of drug treatment in reducing clinical fractures among postmenopausal women with existing vertebral fractures or bone mineral density (BMD) T-scores of −2.5 or lower and among adults aged 50 years and older with recent hip fracture.

Thus, osteoporosis in the clinical setting should be diagnosed in patients with a history of hip or clinical vertebral fracture not due to excessive trauma, those with existing radiographic vertebral fractures, and those with a BMD T-score of −2.5 or lower at the hip (femoral neck or total hip) or lumbar spine. In the absence of a history of hip or vertebral fracture, osteoporosis screening is aimed at identifying individuals with a BMD T-score of −2.5 or lower because those individuals may be candidates for osteoporosis pharmacotherapy. The BMD T-score quantifies the difference (expressed in standard deviations) between a patient’s BMD and the average BMD of young adult white women (reference group).

Author/s:

Crandall, C.J., Ensrud, Kristine E.

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

John Bayhi — Fri, 10 Jan 2020 16:02:17 +0000

Date Added:

January 10, 2020

Journal/Publication:

Lancet

Publisher:

Elsevier Ltd.

Publication Date:

January 11, 2020

Issue:

10218

Volume:

395

Pages:

117-122

URL:

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S0140-6736(19)32955-1

Keywords

breast cancer

anastrozole

female

PMID (1):

31839281

MeSH

cardiovascular diseases

Anastrozole (Arimidex) reduced the long term risk of breast cancer by 50% in women at risk with no major adverse side effects. Menopausal symptoms were increased, primarily during the first year of treatment. James W. Mold, MD, MPH.

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BACKGROUND:

Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period.

METHODS:

IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer.

FINDINGS:

3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed.

INTERPRETATION:

This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.

FUNDING:

Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.

Author/s:

Cuzick, J, Sestak, I, Forbes, JF, Dowsett, M, Cawthorn, S, Mansel, RE, Loibl, S, Bonanni, B, Evans, DG, Howell, A, IBIS-II Investigators

Bisphosphonates for Postmenopausal Osteoporosis

John Bayhi — Sat, 19 Oct 2019 14:38:56 +0000

Date Added:

October 19, 2019

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

October 17, 2019

URL:

Bisphosphonates for Postmenopausal Osteoporosis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2019.15781

Keywords

post-menopausal osteoporosis

bisphosphonates

antiresorptive agents

PMID (1):

31621799

MeSH

Bone Density Conservation Agents

Raloxifene Hydrochloride

Risedronate Sodium

Alendronate

Osteoporosis, Postmenopausal

Selective Estrogen Receptor Modulators

Gatroesophageal Reflux

Estrogens

vitamin D deficiency

Peptic Ulcer

risk reduction behavior

A short, sweet review of how, when, and for how long to treat postmenopausal osteoporosis. James W. Mold, MD, MPH

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Bisphosphonates are the first-line pharmacologic treatment for postmenopausal osteoporosis and the most commonly prescribed medication for this condition.1 Bisphosphonates, classified as antiresorptive agents, have a very high affinity for bone mineral and bind to hydroxyapatite crystals on bony surfaces, where they inhibit osteoclast-mediated bone resorption.

Author/s:

Ensrud, KE, Crandall, CJ

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

John Bayhi — Sat, 31 Aug 2019 15:40:18 +0000

Date Added:

August 31, 2019

Journal/Publication:

The Lancet

Publisher:

Elsevier Ltd.

Publication Date:

August 29, 2019

URL:

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/S0140-6736(19)31709-X

Keywords

MeSH

The relevant information for advising individual patients is covered in the Summary Interpretation section and the last two paragraphs of the Discussion (end of paper).

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Summary

Background

Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.

Methods

Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.

Findings

During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.

Interpretation

If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

Funding

Cancer Research UK and the Medical Research Council.

Author/s:

Collaborative Group on Hormonal Factors in Breast Cancer

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Brian Desmarais — Thu, 23 May 2019 13:11:29 +0000

Date Added:

May 23, 2019

Journal/Publication:

Annals of Internal Medicine

Publisher:

U.S. Department of Health & Human Services

Publication Date:

April 23, 2019

URL:

https://www.ncbi.nlm.nih.gov/pubmed/?term=Long-Term%20Drug%20Therapy%20and%20Dru…

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.7326/M19-0533.

Keywords

MeSH

Raloxifene Hydrochloride

Databases, Bibliographic

National Institutes of Health (U.S.)

Information Storage and Retrieval

bias

Health Services Research

Femoral Fractures

This is a systematic review of current evidence regarding medications for post-menopausal osteoporosis. James W. Mold, MD, MPH

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BACKGROUND:

Optimal long-term osteoporosis drug treatment (ODT) is uncertain.

PURPOSE:

To summarize the effects of long-term ODT and ODT discontinuation and holidays.

DATA SOURCES:

Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.

STUDY SELECTION:

48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).

DATA EXTRACTION:

Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.

DATA SYNTHESIS:

Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapyreduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).

LIMITATION:

No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.

CONCLUSION:

Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-termbisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.

PRIMARY FUNDING SOURCE:

National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Author/s:

Fink, Howard A., MacDonald, Roderick, Forte, Mary L., Rosebush, Christina E., Ensrud, Kristine E., Schousboe, John T., Nelson, Victoria A., Ullman, Kristen, Butler, M., Olson, Carin M., Taylor, Brent C., Brasure, Michelle, Wilt, Timothy J.

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Jeffrey Wilson — Wed, 24 Apr 2019 16:05:48 +0000

Date Added:

April 24, 2019

Journal/Publication:

Comparative Effectiveness Review

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 23, 2019

Issue:

218

URL:

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER218

Keywords

post-menopausal osteoporosis

MeSH

This is a systematic review of current evidence regarding medications for post-menopausal osteoporosis. James W. Mold, MD, MPH

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Objective. To summarize the effects of long-term osteoporosis drug treatment (ODT) and ODT discontinuation and holidays on fractures and harms.

Data sources. MEDLINE®, Embase®, and Cochrane databases from 1995 to October 2018; ClinicalTrials.gov; bibliographies of relevant systematic reviews.

Review methods. We defined long-term ODT as >3 years and ODT holidays as discontinuation for ≥1 year after ≥1 year of use. Trials were used for incident fractures and harms, and controlled observational studies were included for additional harms. Two investigators rated risk of bias. For studies with low or medium risk of bias, one investigator extracted data and a second verified accuracy. Two investigators graded strength of evidence (SOE).

Results. Sixty-one English-language studies were included. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR] 0.64 [95% confidence interval (CI) 0.50, 0.82]) (moderate SOE) and radiographic vertebral fractures (HR 0.50 [95% CI 0.31, 0.82]) (moderate SOE), while 4 years of raloxifene reduced clinical vertebral fractures (relative risk 0.58 [95% CI 0.43, 0.79]) (high SOE), but not hip (moderate SOE) or nonvertebral fractures (high SOE). In women with osteopenia or osteoporosis, 6 years of zoledronate reduced incident clinical fractures (HR 0.73 [95% CI 0.60, 0.90]) (moderate SOE) and clinical vertebral fractures (HR 0.41 [95% CI 0.22, 0.75]) (moderate SOE). In postmenopausal women with unknown osteoporosis or osteopenia status, both long-term oral estrogen and estrogen/progestin reduced clinical fractures (high SOE) and hip fractures (moderate SOE). After 3–5 years of prior treatment, continuation of zoledronate or alendronate versus drug holiday inconsistently reduced incident vertebral fracture outcomes (radiographic only for zoledronate [low SOE], clinical only for alendronate [moderate SOE]), but did not reduce nonvertebral fractures (low SOE). Hormone therapies increased cardiovascular events, mild cognitive impairment or dementia, and other harms. Observational studies showed that long-term bisphosphonates may increase atypical femoral fractures (AFF) (low SOE) and osteonecrosis of the jaw (low SOE in 2 comparisons, insufficient in 1).

Limitations. Most data were from white, healthy, postmenopausal women, limiting generalizability. Trials often had low power for incident clinical fractures. No trials compared active treatments, sequential treatments, or different durations of drug holidays. Harms and controls were inconsistently defined.

Conclusions. Long-term alendronate, zoledronate, and oral hormone therapy reduced nonvertebral fractures in older women, with oral hormone therapy also reducing hip fractures. While absolute reductions in typical fractures with long-term bisphosphonates are large relative to increases in AFF, reduced hip fracture risk with oral hormone therapy appears offset by increased risk of serious harms. Evidence is limited regarding ODT holidays for fractures and harms. Future research is needed, including randomized trials comparing ODT holiday durations and sequential treatments powered for clinical fractures, and controlled cohort studies of ODT holidays to estimate rare harms.

Author/s:

Fink, Howard A., MacDonald, Roderick, Forte, Mary L., Rosebush, Christina E., Ensrud, Kristine E., Schousboe, John T., Nelson, Victoria A., Ullman, Kristen, Butler, Mary, Olson, Carin M., Taylor, Brent C., Brasure, Michelle, Wilt, Timothy J.

Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial

Jeffrey Wilson — Wed, 22 Aug 2018 17:00:33 +0000

Date Added:

November 1, 2018

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

May 1, 2018

Issue:

Volume:

178

Pages:

681-690

URL:

Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2018.0116

Keywords

postmenopause

estradiol

moisturizing gel

PMID (1):

29554173

MeSH

postmenopause

vaginal creams, foams, and jellies

estradiol

In this RCT, vaginal estradiol was no more effective than moisturizing gel for postmenopausal vaginal symptoms.

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IMPORTANCE:

Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments.

OBJECTIVE:

To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms.

DESIGN, SETTING, AND PARTICIPANTS:

This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration.

INTERVENTIONS:

Vaginal 10-μg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100).

MAIN OUTCOMES AND MEASURES:

The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score-Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH.

RESULTS:

The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, -1.4 (95% CI, -1.6 to -1.2); moisturizer, -1.2 (95% CI, -1.4 to -1.0); and placebo, -1.3 (95% CI, -1.5 to -1.1). No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) (P = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P = .17).

CONCLUSIONS AND RELEVANCE:

Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms.

Author/s:

Mitchell, Caroline M., Reed, Susan D., Diem, Susan, Larson, Joseph C., Newton, Katherine M., Ensrud, Kristine E., LaCroix, Andrea Z., Caan, Bette, Guthrie, Katherine A.