The HRT controversy: observational studies and RCTs fall in line

  title={The HRT controversy: observational studies and RCTs fall in line},
  author={Jan Paul Vandenbroucke},
  journal={The Lancet},

Summarising the Evidence for Drug Safety: A Methodological Discussion of Different Meta-Analysis Approaches

The different data sources for summarising drug safety outcomes, according to study design, publication of data, and origin of the information are reviewed, focusing on meta-analyses of aggregate data and meta-Analyses of individual patient data.

Exercise training and vascular function in postmenopausal individuals: a systematic review and meta-analysis

It is shown that flow-mediated dilation is increased with aerobic exercise training in postmenopausal individuals and that this benefit might be more prevalent for women with a higher resting blood pressure and the greatest improvement in aerobic fitness.

HRP_220057 215..225

  • 2022

Menopausal Hormone Therapy and the Mind: The Role of Hormone Replacement in the Prevention and Treatment of Cognitive Decline, Dementia, and Cognitive Dysfunction of Depression

The neurobiological effects of MHT are synthesized, recommendations for its use in current clinical practice in the contexts of cognitive dysfunction associated with major depressive disorder, cognitive decline, and Alzheimer’s disease are made, and the frontiers being explored by ongoing research on this topic are discussed.

Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study

Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with

Association between menopausal hormone therapy use and mortality risk: a Swedish population-based matched cohort study

The generalisable data suggest that early menopausal hormone treatment initiation does not increase the odds of mortality, and the role of oestrogens in particularly cardiovascular mortality remains to be investigated.

Medications for chronic obstructive pulmonary disease: a historical non-interventional cohort study with validation against RCT results.

Data from the TORCH randomised controlled trial was used to validate non-interventional methods for assessing the clinical effectiveness of chronic obstructive pulmonary disease treatment in the UK Clinical Practice Research Datalink and to determine treatment effects in people who would have been excluded from the TorCH trial.

Low intraoperative end-tidal carbon dioxide: a promising target to improve outcomes or a marker of physiologic instability?

This thought-provoking study has many strengths, including a large data set with measurement of ETCO2 every 60 sec that allowed for an assessment of a cumulative effect and key confounders, including mean arterial blood pressure, were identified and controlled for in the statistical model.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

This study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice and investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality.



Authorʼs Response, Part II

The overall Women's Health Initiative results for CHD should not be generalized to the majority of women who start hormone therapy near the time of menopause, and correspondingly the overall results of the NHS and other observational results should not been generalized to women starting hormone use many years afterMenopause.

The sound and the fury: was it all worth it?

The initial report of coronary heart disease (CHD) results from the trial of menopausal hormone therapy within the Women's Health Initiative precipitated substantial surprise and concern in the

Data analysis methods and the reliability of analytic epidemiologic research.

Analysis of randomized controlled trial and cohort study results on the effects of postmenopausal estrogen-plus-progestin therapy illustrates the potential of modern data analysis methods to enhance the reliability and interpretation of epidemiologic data.

ITT for observational data: worst of both worlds?

It is concluded that differences in time since menopause remains the most plausible explanation for the different findings compared with findings from the Women's Health Initiative Trial.

Benefits and risks of drug treatments: how to combine the best evidence on benefits with the best data about adverse effects.

To understand the full spectrum of adverse effects—those that occur late, that were not known beforehand, and that are rare but nevertheless serious—and to be able to investigate the true incidence of known adverse effects in circumstances of actual prescribing, well-designed observational studies will always be necessary.

Observational data and clinical trials: narrowing the gap?

An ambitious paper by Hernán et al, in which a new analysis of the Nurses’ Health Study provides results consistent with the randomized trial, is published, followed by 3 commentaries (by Hoover, Stampfer, and Prentice) and responses from the authors.

Combined postmenopausal hormone therapy and cardiovascular disease: toward resolving the discrepancy between observational studies and the Women's Health Initiative clinical trial.

Hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment, although there was evidence of some remaining difference for stroke.

Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease.

For coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin.