Systemic Menopausal Hormone Therapy Research Articles

Menopausal hormone therapy and cancer risk: An overestimated risk?

AimWe aimed to assess the overall cancer risk among contemporary menopausal hormone therapy (MHT) users in Sweden and the risk for different cancer types. MethodsA nationwide Swedish population-based cohort study including all 290,186 women aged ≥ 40 years having used systemic MHT during the study period (July 2005 and December 2012), compared with the Swedish female background population. MHT ever-use (all MHT, oestrogen-only MHT [E-MHT] and oestrogen plus progestin MHT [EP-MHT]) was based on the nationwide Prescribed Drug Registry. Cancer diagnoses were grouped into 16 different anatomical locations, for which standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. ResultsThe SIR of any cancer was 1.09 (95% CI: 1.07–1.11) following ever MHT, 1.04 (95% CI: 1.01–1.06) for E-MHT and 1.14 (95% CI: 1.12–1.17) for EP-MHT. The highest SIR was found for EP-MHT among users aged ≥70 years (SIR = 1.33, 95% CI: 1.26–1.40). The risk for invasive breast, endometrial or ovarian cancer combined was increased for any MHT (SIR = 1.31, 95% CI: 1.28–1.34). The risk of invasive breast cancer was increased following MHT and increased with age for EP-MHT users. The risk of gastrointestinal cancers combined was decreased (SIR = 0.90, 95% CI: 0.86–0.94), particularly the oesophagus (SIR = 0.81, 95% CI: 0.64–1.00), liver (SIR = 0.81, 95% CI: 0.65–0.99) and colon (SIR = 0.90, 95% CI: 0.84–0.95). ConclusionsMHT, notably EP-MHT, was associated with a limited increase in overall cancer risk. The increased risk of female reproductive organ cancers was almost balanced by a decreased risk of gastrointestinal cancers.

Menopausal hormone therapy and the risk of esophageal and gastric cancer.

A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR = 0.62, 95% CI 0.45-0.85, n = 46), gastric adenocarcinoma (OR = 0.61, 95% CI 0.50-0.74, n = 123) and esophageal squamous cell carcinoma (OR = 0.57, 95% CI 0.39-0.83, n = 33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR = 0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.

Is there a time limit for systemic menopausal hormone therapy?

In deciding whether it is time to stop hormone therapy, in addition to the patient's age we need to consider her preferences, symptoms, quality of life, time since menopause, hysterectomy status, and personal risks of osteoporosis, breast cancer, heart disease, stroke, and venous thromboembolism. This article presents the evidence for and against extending hormone therapy and a guide for making this highly individualized and shared decision.

Prescribing menopausal hormone therapy: an evidence-based approach

The constantly changing landscape regarding menopausal hormone therapy (MHT) has been challenging for providers caring for menopausal women. After a decade of fear and uncertainty regarding MHT, reanalysis of the Women’s Health Initiative data and the results of recent studies have provided some clarity regarding the balance of risks and benefits of systemic MHT. Age and years since menopause are now known to be important variables affecting the benefit-risk profile. For symptomatic menopausal women who are under 60 years of age or within 10 years of menopause, the benefits of MHT generally outweigh the risks. Systemic MHT initiated early in menopause appears to slow the progression of atherosclerotic disease, thereby reducing the risk of cardiovascular disease and mortality. During this window of opportunity, MHT might also provide protection against cognitive decline. In older women and women more than 10 years past menopause, the risk-benefit balance of MHT is less favorable, particularly with regard to cardiovascular risk and cognitive impairment. For women entering menopause prematurely (<40 years), MHT ameliorates the risk of cardiovascular disease, osteoporosis, and cognitive decline. Nonoral administration of estrogen offers advantages due to the lack of first-pass hepatic metabolism, which in turn avoids the increased hepatic synthesis of clotting proteins, C-reactive protein, triglycerides, and sex hormone-binding globulin. The duration of combined MHT use is ideally limited to less than 5 years because of the known increase in breast cancer risk after 3–5 years of use. Limitations to use of estrogen only MHT are less clear, since breast cancer risk does not appear to increase with use of estrogen alone. For women under the age of 60 years, or within 10 years of onset of natural menopause, MHT for the treatment of bothersome menopausal symptoms poses low risk and is an acceptable option, particularly when nonhormonal management approaches fail.

Global Consensus Statement on menopausal hormone therapy

MediClinic Panorama and Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa; * Department of Surgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, OH, USA; † Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR; ‡ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; * * Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA; † † University of Geneva, Switzerland; ‡ ‡ Reader Emeritus, University of Oxford, UK

Trends in menopausal hormone therapy use of US office-based physicians, 2000-2009.

The aim of this study was to evaluate recent trends and the adoption of practice recommendations for menopausal hormone therapy (MHT) use from 2001 to 2009 by formulation, dose, woman's age, and characteristics of physicians reporting MHT visits. The IMS Health (Plymouth Meeting PA) National Disease and Therapeutic Index physician survey data from 2001 to 2009 were analyzed for visits in which MHT use was reported by US office-based physicians. Estimated national volume of visits for which MHT use was reported. MHT use declined each year since 2002. Systemic MHT use fell from 16.3 million (M) visits in 2001 to 6.1 M visits in 2009. Declines were greatest for women 60 years or older (64%) but were also substantial for women younger than 50 years (59%) and women 50 to 59 years old (60%). Women 60 years or older accounted for 37% of MHT use. Lower dose product use increased modestly, from 0.7 M (2001) to 1.3 M (2009), as did vaginal MHT use, from 1.8 M (2001) to 2.4 M (2009). Declines in continuing systemic MHT use (65%) were greater than for newly initiated MHT use (51%). Compared with other physicians, obstetrician/gynecologists changed their practices less, thereby increasing their overall share of total MHT visits from 72% (2001) to 82% (2009). Total MHT use has steadily declined. Increased use of lower dose and vaginal products reflects clinical recommendations. Uptake of these products, however, has been modest, and substantial use of MHT continues in older women.