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CMAJ : Canadian Medical Association... Aug 2021
Topics: Adolescent; Bone Density; Canada; Contraception; Contraceptive Agents, Female; Desogestrel; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Long-Acting Reversible Contraception; Medroxyprogesterone Acetate; Pregnancy; Pregnancy, Unplanned; Sexually Transmitted Diseases
PubMed: 34373270
DOI: 10.1503/cmaj.202413 -
JAMA Sep 2017Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.
OBJECTIVE
To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.
DESIGN, SETTING, AND PARTICIPANTS
Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.
INTERVENTIONS
Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).
MAIN OUTCOMES AND MEASURES
All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.
RESULTS
Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.
CONCLUSIONS AND RELEVANCE
Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00000611.
Topics: Aged; Cardiovascular Diseases; Cause of Death; Double-Blind Method; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Follow-Up Studies; Humans; Medroxyprogesterone; Middle Aged; Mortality; Neoplasms; Postmenopause; Risk
PubMed: 28898378
DOI: 10.1001/jama.2017.11217 -
Mayo Clinic Proceedings Jul 2011The change in hormonal milieu associated with perimenopause and menopause can lead to a variety of symptoms that can affect a woman's quality of life. Postmenopausal... (Review)
Review
The change in hormonal milieu associated with perimenopause and menopause can lead to a variety of symptoms that can affect a woman's quality of life. Postmenopausal hormone therapy (HT) is an effective, well-tolerated treatment for these symptoms. However, combined HT consisting of conjugated equine estrogen and medroxyprogesterone acetate has been associated with an increased number of health risks when compared with conjugated equine estrogen alone or placebo. As a result, some women are turning to alternative hormonal formulations known as compounded bioidentical HT because they perceive them to be a safer alternative. This article defines compounded bioidentical HT and explores the similarities and differences between it and US Food and Drug Administration-approved HT. We will examine the major claims made by proponents of compounded bioidentical HT and recommend strategies for management of patients who request bioidentical HT from physicians.
Topics: Drug Approval; Estradiol; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Medroxyprogesterone Acetate; Progestins; United States
PubMed: 21531972
DOI: 10.4065/mcp.2010.0714 -
BMJ (Clinical Research Ed.) Jan 2019To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy. (Comparative Study)
Comparative Study Observational Study
OBJECTIVE
To assess the association between risk of venous thromboembolism and use of different types of hormone replacement therapy.
DESIGN
Two nested case-control studies.
SETTING
UK general practices contributing to the QResearch or Clinical Practice Research Datalink (CPRD) databases, and linked to hospital, mortality, and social deprivation data.
PARTICIPANTS
80 396 women aged 40-79 with a primary diagnosis of venous thromboembolism between 1998 and 2017, matched by age, general practice, and index date to 391 494 female controls.
MAIN OUTCOME MEASURES
Venous thromboembolism recorded on general practice, mortality, or hospital records. Odds ratios were adjusted for demographics, smoking status, alcohol consumption, comorbidities, recent medical events, and other prescribed drugs.
RESULTS
Overall, 5795 (7.2%) women who had venous thromboembolism and 21 670 (5.5%) controls had been exposed to hormone replacement therapy within 90 days before the index date. Of these two groups, 4915 (85%)and 16 938 (78%) women used oral therapy, respectively, which was associated with a significantly increased risk of venous thromboembolism compared with no exposure (adjusted odds ratio 1.58, 95% confidence interval 1.52 to 1.64), for both oestrogen only preparations (1.40, 1.32 to 1.48) and combined preparations (1.73, 1.65 to 1.81). Estradiol had a lower risk than conjugated equine oestrogen for oestrogen only preparations (0.85, 0.76 to 0.95) and combined preparations (0.83, 0.76 to 0.91). Compared with no exposure, conjugated equine oestrogen with medroxyprogesterone acetate had the highest risk (2.10, 1.92 to 2.31), and estradiol with dydrogesterone had the lowest risk (1.18, 0.98 to 1.42). Transdermal preparations were not associated with risk of venous thromboembolism, which was consistent for different regimens (overall adjusted odds ratio 0.93, 95% confidence interval 0.87 to 1.01).
CONCLUSIONS
In the present study, transdermal treatment was the safest type of hormone replacement therapy when risk of venous thromboembolism was assessed. Transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.
Topics: Administration, Cutaneous; Adult; Aged; Case-Control Studies; Estrogens; Female; Hormone Replacement Therapy; Humans; Medroxyprogesterone Acetate; Menopause; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; United Kingdom; Venous Thromboembolism
PubMed: 30626577
DOI: 10.1136/bmj.k4810 -
Steroids Nov 2022Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to understand progestin pharmacokinetics and to correct for... (Review)
Review
Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to understand progestin pharmacokinetics and to correct for unreliable self-reporting of contraceptive use by study participants. Many such studies are focussed on the three-monthly progestin-only intramuscular (IM) injectable contraceptive depot medroxyprogesterone acetate (DMPA-IM). Methods commonly used to measure serum MPA levels include liquid chromatography coupled to mass spectrometry (LC/MS) and radioimmunoassay (RIA); however, RIA methods have not been used in recent years. We review the available literature and find that these methods vary widely in terms of use of organic solvent extraction, use of derivitization and choice of organic solvent and chromatography columns. There is a lack of standardization of LC/MS methodology, including a lack of detailed extraction protocols. Limited evidence suggests that RIA, without organic solvent extraction, likely over-estimates progestin levels. Maximum MPA concentrations in the first two weeks post-injection show wide inter-individual and inter-study variation, regardless of quantification method used. Standardization of quantification methods and sampling time post-injection is required to improve interpretation of clinical data, in particular the side effects arising at different times depending on the pharmacokinetic profile unique to injectable contraceptives.
Topics: Contraceptive Agents; Contraceptive Agents, Female; Female; Humans; Medroxyprogesterone Acetate; Progestins; Radioimmunoassay; Solvents
PubMed: 35964796
DOI: 10.1016/j.steroids.2022.109100 -
Obstetrics and Gynecology May 2022Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.
OBJECTIVE
Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.
METHODS
We conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.
RESULTS
Of participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).
CONCLUSION
Recent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.
Topics: Cohort Studies; Contraceptive Agents, Female; Delayed-Action Preparations; Female; Humans; Incidence; Leiomyoma; Medroxyprogesterone; Medroxyprogesterone Acetate
PubMed: 35576339
DOI: 10.1097/AOG.0000000000004745 -
Women's Health (London, England) Jan 2016Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of... (Review)
Review
Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations.
Topics: Antifibrinolytic Agents; Contraceptives, Oral, Hormonal; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Medroxyprogesterone; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Women's Health
PubMed: 26695687
DOI: 10.2217/whe.15.100 -
The Western Journal of Medicine Mar 1982Hormone-replacement therapy for postmenopausal women has associated benefits and risks. The advantages of the administration of estrogen to postmenopausal women include...
Hormone-replacement therapy for postmenopausal women has associated benefits and risks. The advantages of the administration of estrogen to postmenopausal women include preventing or reversing the atrophic changes of the genitourinary system, slowing of facial aging, relieving hot flushes and psychological symptoms, preventing atherosclerotic heart disease and retarding the development of osteoporosis. The disadvantages of the administration of estrogen to postmenopausal women include rare but serious clinical sequelae associated with the ingestion of the synthetic estrogen when it is one component of the combination oral contraceptives, increased risk of cancer developing in the estrogen-dependent organs and uterine bleeding. The benefits of long-term cyclic estrogen-gestagen therapy in preventing osteoporosis far outweigh the risks.
Topics: Adult; Aging; Arteriosclerosis; Calcium; Climacteric; Estrogens; Female; Humans; Medroxyprogesterone; Menopause; Middle Aged; Osteoporosis
PubMed: 7090370
DOI: No ID Found -
Global Health, Science and Practice Mar 2018DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many...
DMPA-SC is a contraceptive injectable formulation that provides women and couples another important voluntary family planning option. It offers characteristics that many women like, including cost and time savings, and has the potential to be delivered by a range of health care cadres in a variety of service delivery channels.
Topics: Contraception; Contraceptive Agents; Contraceptive Agents, Female; Humans; Injections; Medroxyprogesterone Acetate
PubMed: 29602863
DOI: 10.9745/GHSP-D-18-00050 -
BMJ Global Health Jul 2022Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an innovative contraceptive method aimed at meeting women's unique circumstances and needs, largely due to... (Review)
Review
Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is an innovative contraceptive method aimed at meeting women's unique circumstances and needs, largely due to its ability to be self-injected. Substantial research and advocacy investments have been made to promote roll-out of DMPA-SC across sub-Saharan Africa. To date, research on the demand for DMPA-SC as a self-injectable method has been conducted largely with healthcare providers, via qualitative research, or with highly specific subsamples that are not population based. Using three recent rounds of data from Performance Monitoring for Action, we examined population-representative trends in demand, use, and preference for self-injection among current non-users in Burkina Faso, the Democratic Republic of Congo (Kinshasa and Kongo Central regions), Kenya, and Nigeria (Lagos and Kano States). We found that while over 80.0% of women had heard of injectables across settings, few women had heard of self-injection (ranging from 13.0% in Kenya to 24.8% in Burkina Faso). Despite initial increases in DMPA-SC prevalence, DMPA-SC usage began to stagnate or even decrease in all settings in the recent three years (except in Nigeria-Kano). Few (0.0%-16.7%) current DMPA-SC users were self-injecting, and the majority instead were relying on a healthcare provider for administration of DMPA-SC. Among current contraceptive non-users wishing to use an injectable in the future, only 1.5%-11.4% preferred to self-inject. Our results show that self-injection is uncommon, and demand for self-injection is very limited across six settings, calling for further qualitative and quantitative research on women's views on DMPA-SC and self-injection and, ultimately, their contraceptive preferences and needs.
Topics: Contraceptive Agents, Female; Democratic Republic of the Congo; Female; Humans; Injections, Subcutaneous; Medroxyprogesterone Acetate; Nigeria; Self Administration
PubMed: 35835480
DOI: 10.1136/bmjgh-2022-008862