Estrogens and Progestin'S: Backdrop and Narration, Inclinations in Utilize, and Strategies and Scheduled Accepted by the Us Food and Drug Management (original) (raw)
Related papers
Failure of estrogen plus progestin therapy for prevention
JAMA : the journal of the American Medical Association, 2002
A PPROXIMATELY 38% OF POSTMENOPAUSAL WOMEN in the United States use hormone replacement therapy. 1 In 2000, 46 million prescriptions were written for Premarin (conjugated estrogens), making it the second most frequently prescribed medication in the United States and accounting for more than $1 billion in sales, and 22.3 million prescriptions were written for Prempro (conjugated estrogens plus medroxyprogesterone acetate). 2 While US Food and Drug Administrationapproved indications for hormone therapy include relief of menopausal symptoms and prevention of osteoporosis, longterm use has been in vogue to prevent a range of chronic conditions, especially heart disease. Estrogen alone was the dominant hormone until the increased risk of endometrial cancer led to the addition of progestins for women with an intact uterus. Since the mid-1980s, combined estrogen/ progestin use has steadily increased. Evidence on the potential risks and benefits of combined estrogen/progestin has slowly accumulated, suggesting that the combination acts differently than estrogen alone. Several studies found a link between duration of estrogen/ progestin use and breast cancer risk. 4-8 Addition of progestins may increase risk above that observed with estrogen alone, as mitotic activity in the breast during normal menstrual cycles is greatest when progesterone levels are highest. Early evidence from studies of unopposed estrogen suggested it lowered risk of cardiovascular disease, consistent with results from studies of intermediate markers that showed beneficial changes. 10 However, recent evidence from secondary prevention trials and observational studies using combined estrogen/progestin therapy showed increased risk of coronary heart disease in the first year. 11-13 This may reflect prothrombotic and proinflammatory effects of progestins that outweigh any effects of estrogens on atherogenesis and vasodilatation. Now, the surprising results of the Women's Health Initiative (WHI) are reported in this issue of THE JOURNAL. 14 The WHI is the first randomized primary prevention trial of postmenopausal hormones, and the part of the study that compared estrogen/progestin with placebo was terminated early. The data and safety monitoring board (DSMB) recommended stopping the trial because women receiving the active drug had an increased risk of invasive breast cancer (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.00-1.59), and an overall measure suggested that the treatment was causing more harm than good (global index, 1.15; 95% CI, 1.03-1.28). The decision to stop the trial after an average follow-up of 5.2 years (planned duration, 8.5 years) was made when these results met predetermined levels of harm. However, several other outcomes also suggested harm, including increased coronary heart disease (HR, 1.29; 95% CI, 1.02-1.63), stroke (HR, 1.41; 95% CI, 1.07-1.85), and pulmonary embolism (HR, 2.13; 95% CI, 1.39-3.25). Beneficial results included decreases in colorectal cancer (HR, 0.63, 95% CI, 0.43-0.92) and hip fracture (HR, 0.66; 95% CI, 0.45-0.98). Numbers of overall deaths in the estrogen/ progestin and placebo groups were statistically and clinically similar in this short-duration study. Most adverse outcomes began appearing within 1 to 2 years, but increased breast cancer risk did not begin until 3 years. Results were remarkably consistent in subgroup analyses, suggesting that there is not a subgroup that the drug benefits.
Annals of the New York Academy of Sciences, 2005
Recent clinical trials in hormone therapy (HT) for women approaching or past menopause have been disappointing. Most women who have been taking conjugated equine estrogens combined with synthetic progestins have been encouraged to stop these supplements because of increased health risks. The results of the clinical trials may be accurate about the risks associated with the synthetic compounds and combinations, but the data do not reflect what might have been the case if 17estradiol had been tested with natural progesterone instead of synthetic medroxyprogesterone acetate. For the most part, in almost all work on HT, estrogens have been given the primary focus despite the fact that progesterone has important properties that can enhance the repair of neurodegenerative and traumatic injuries to the central nervous system. This article reviews some of those properties and discusses the evidence suggesting that, if HT is to be reconsidered, progesterone should be given more attention as a potent neurotrophic agent that may play an important role in reducing or preventing motor, cognitive, and sensory impairments that can accompany senescence in both males and females.
2007
Objective: To update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2004 regarding recommendations for estrogen and progestogen use in peri-and postmenopausal women. Design: NAMS followed the general principles established for evidence-based guidelines to create this updated document. An Advisory Panel of clinicians and researchers expert in the field of women`s health was enlisted to review the 2004 NAMS position statement, compile supporting statements, and reach consensus on recommendations. The Panel`s recommendations were reviewed and approved by the NAMS Board of Trustees. The position statements published by NAMS do not represent Bpractice standards^that would be codified and held up as standards by regulating bodies and insurance agencies. Rather, they are prevailing opinion pieces in a best effort attempt to incorporate current evidence into practical clinical recommendations. Results: With the primary goal being to evaluate the risk-benefit ratio of peri-and postmenopausal estrogen therapy (ET) and estrogen-progestogen therapy (EPT) for both disease prevention and treatment of menopause-related symptoms, current evidence allowed for a clear distinction between areas of consensus and areas for which the Panel determined that there was inadequate evidence for any conclusion to be reached. The document lists all of these areas along with clear explanatory comments. A comprehensive list of key references is provided. The absence of evidence is also recognized in the list of needs for further research recommended by the Panel. Conclusions: Current evidence supports the use of ET or EPT for menopause-related symptoms and disease prevention in appropriate populations of peri-and postmenopausal women.
Estrogen and progestogen use in peri- and postmenopausal women
Menopause, 2007
Objective: To update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2004 regarding recommendations for estrogen and progestogen use in peri-and postmenopausal women. Design: NAMS followed the general principles established for evidence-based guidelines to create this updated document. An Advisory Panel of clinicians and researchers expert in the field of women`s health was enlisted to review the 2004 NAMS position statement, compile supporting statements, and reach consensus on recommendations. The Panel`s recommendations were reviewed and approved by the NAMS Board of Trustees. The position statements published by NAMS do not represent Bpractice standards^that would be codified and held up as standards by regulating bodies and insurance agencies. Rather, they are prevailing opinion pieces in a best effort attempt to incorporate current evidence into practical clinical recommendations. Results: With the primary goal being to evaluate the risk-benefit ratio of peri-and postmenopausal estrogen therapy (ET) and estrogen-progestogen therapy (EPT) for both disease prevention and treatment of menopause-related symptoms, current evidence allowed for a clear distinction between areas of consensus and areas for which the Panel determined that there was inadequate evidence for any conclusion to be reached. The document lists all of these areas along with clear explanatory comments. A comprehensive list of key references is provided. The absence of evidence is also recognized in the list of needs for further research recommended by the Panel. Conclusions: Current evidence supports the use of ET or EPT for menopause-related symptoms and disease prevention in appropriate populations of peri-and postmenopausal women.
Women’s Health Initiative estrogen plus progestin clinical trial
Menopause, 2015
Objective: This study aims to determine time differences (differences in restricted mean survival times [RMSTs]) in the onset of invasive breast cancer, coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip fracture between the placebo group and the conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg group of the Women_s Health Initiative (WHI) trial based on survival curves of the original report and to provide adequate interpretation of the clinical effects of a given intervention. Methods: Distribution of survival function was obtained from cumulative hazard plots of the WHI report; Monte Carlo simulation was performed to obtain censored observations for each outcome, in which assumptions of the Cox model were evaluated once corresponding hazard ratios had been estimated. Using estimation methods such as numerical integration, pseudovalues, and flexible parametric modeling, we determined differences in RMSTs for each outcome. Results: Obtained cumulative hazard plots, hazard ratios, and outcome rates from the simulated model did not show differences in relation to the original WHI report. The differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17 days (95% CI, j2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90 to 12.11) for coronary heart disease, 2.75 days (95% CI, j0.84 to 6.34) for stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, j2.73 days (95% CI, j5.32 to j0.13) for colorectal cancer, and j2.77 days (95% CI, j5.44 to j0.1) for hip fracture. Conclusions: The differences in RMST for the outcomes of the WHI study are too small to establish clinical risks related to hormone therapy use.
Biomedicines
Estrogen is one of the most important female sex hormones, and is indispensable for reproduction. However, its role is much wider. Among others, due to its neuroprotective effects, estrogen protects the brain against dementia and complications of traumatic injury. Previously, it was used mainly as a therapeutic option for influencing the menstrual cycle and treating menopausal symptoms. Unfortunately, hormone replacement therapy might be associated with detrimental side effects, such as increased risk of stroke and breast cancer, raising concerns about its safety. Thus, tissue-selective and non-classical estrogen analogues have become the focus of interest. Here, we review the current knowledge about estrogen effects in a broader sense, and the possibility of using selective estrogen-receptor modulators (SERMs), selective estrogen-receptor downregulators (SERDs), phytoestrogens, and activators of non-genomic estrogen-like signaling (ANGELS) molecules as treatment.
2009
The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administra- tion and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective. Objective: This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the com- monly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease. Methods: Publishe...