Hormones are chemical messengers of the body which communicate with tissues and the bloodstream. Hormones affect a variety of bodily functions, including growth and development, metabolism—the process through which the body converts food into energy—sexual function, reproduction, and mood. Diseases that can have an impact on a variety of facets of life emerge when glands do not produce the appropriate quantity of hormones. Puberty, aging, pregnancy, the environment, heredity, and some diseases and medications, such as naturopathic medicine, herbal supplements, and prescription drugs like opioids or steroids, are some elements that have an impact on the endocrine system. Physical and mental health depend on hormones. Hormone therapy is carried out due to little or a lack of hormones in the body. Female menopause symptoms are treated with hormone replacement treatment (HRT), commonly referred to as menopausal hormone therapy or postmenopausal hormone therapy. The two hormone medications most commonly used in hormone replacement therapy are estrogens and progestogens.
History behind HRT
Table of Contents
Menopausal disorders have drawn more attention in the 20th century, although it took a while for researchers to understand the true effects of hormone depletion on women’s health. It included symptoms like hot flashes, cardiovascular events, Alzheimer’s disease, and vaginal atrophy. They were collectively referred to as “Hormone Deficiency Syndrome”. At the beginning of the 20th century, the Food and Drug Administration (FDA) approved an estrogen product for the first time, Preamirin®, for the treatment of hot flashes. With the idea of “feminine forever,” the feminist movement in the 1960s improved the position of women and their life expectancy while also advocating menopause therapy, particularly in European nations. Hormone replacement therapy (HRT) was promoted as a treatment that may help women escape the perils of estrogen deficiency and maintain their femininity. The discovery that unopposed estrogen supplements were linked to a higher risk of endometrial cancer in the 1970s had a negative effect on HRT’s reputation. But in the years that followed, scientists learned that lowering estrogen levels and mixing them with progesterone could lower the risk of endometrial cancer. This type of combination therapy was suggested for those with an intact uterus, rekindling interest in HRT treatment. Osteoporosis prevention was added to the list of FDA-approved indications for HRT in 1988 after initially only being licensed by the agency for the treatment of hot flashes.
The controversy
The Women’s Health Initiative (WHI), the biggest randomized trial to date that evaluated the impact of HRT on the most prevalent causes of mortality and disability in postmenopausal women, including cardiovascular disease, cancer, and osteoporosis, was launched in 1998. Women without uteri (10,739 participants) received 0.625 mg of conjugated equine estrogen(CEE) or a placebo, while women with uteri (16,608 participants) received 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate. The WHI’s initial findings were released in 2002 after an average follow-up of 5.2 years. The incidence of breast cancer and coronary heart disease increased in the group of women with intact uteri, while osteoporotic fractures and colon cancer decreased. With these findings, it appeared that the risks outweighed the advantages, and the research was abruptly stopped. The statistics were widely reported in the media, which caused alarm among HRT users and forced medical professionals to change their recommendations for HRT prescriptions. The message was that HRT had more hazards than advantages and didn’t specify the type or mode of administration. Yet, there was no distinction in users’ ages.
The only-estrogen trial (conducted on women who underwent hysterectomy) went on, and the early findings were released in 2004. However, this trial was terminated early after just 6.8 years of follow-up because there was evidence of a little increase in the risk of an ischemic stroke without any other appreciable cardiovascular benefits. The overall message on HRT remained unfavorable despite the advantages such as a decreased risk of osteoporotic fracture and colon cancer. After these revelations, the UK regulatory authorities issued an emergency safety restriction regarding HRT, advising physicians to only use it as a second-line treatment for the prevention of osteoporosis and not to provide it to asymptomatic postmenopausal women. Since then, numerous WHI findings have been the subject of heated debates and ongoing arguments over the study’s methodology and findings. The majority of the participants in the WHI were found to be more than ten years past their last menstrual cycle, which brought up the issue of whether the trial’s findings could be generalized to younger women. This turned out to be a key drawback of the WHI.
The WHI also only examined CEE, either by itself or in conjunction with the progestin medroxyprogesterone acetate. The WHI results did not resolve questions regarding the efficacy and safety of different HRT formulations, regimens, and delivery techniques. Notwithstanding its flaws, the WHI had a detrimental effect on how HRT was perceived around the world and significantly decreased the use of HRT. Several medical professionals stopped recommending HRT, and many women stopped using it right away.
The WHI was followed up on for an additional 13 years, and certain findings, such as an age stratification of the cardiovascular outcomes, were published in the years that followed. The use of HRT in younger women (50-59 years old) or early postmenopausal women (within 10 years of menopausal onset) had a positive effect on the cardiovascular system, lowering coronary diseases and all-cause mortality, according to a reanalysis of the WHI trial with new studies and a metanalysis. Similarly, a significant controlled Danish study from 2012 found that healthy women taking combined HRT for 10 years after menopause had a lower chance of developing heart disease and dying from it. Sadly, the media did not properly publish these findings, and the stigma around HRT has lingered.
Conclusion
The contentious history of HRT concerns the development of a potent pathogenetic therapy for all postmenopausal disorders. The treatment’s effects on the symptoms are and were immediately apparent, which initially led to rapidly rising estrogen use. Consequences that restricted the use of HRT were brought about by a lack of information about its adverse effects and problems, notably in the endometrium. However, further research and analyses have supported the idea that HRT is quite helpful for symptomatic women who are under 60 years old or who have experienced menopause within the past 10 years.
References
The Controversial History of Hormone Replacement Therapy
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