Why Hormone Replacement Therapy May Be Safer Than You ThinkJan 04, Author: However, HT has been linked to various risks; debate regarding its risk-benefit ratio continues. Changes and Challengesa Critical Images slideshow, to help hornone comorbidities theray diseases in the postmenopausal population. The spectrum and intensity of perimenopausal and menopausal symptoms vary greatly due to the effect of decreased circulating levels of estrogen on various organ systems. Other common presenting symptoms include the following:. HT can be prescribed hormone therapy for menopause local creams, pessaries, rings or systemic therapy oral drugs, transdermal patches and gels, implants. Hormonal products available in such preparations may hormone therapy for menopause the following ingredients:.
Here's what you should know about hormone therapy for menopause | Popular Science
Hormone replacement therapy HRT in menopause is medical treatment in postmenopausal , perimenopausal , and surgically menopausal women. Its goal is to mitigate discomfort caused by diminished circulating estrogens and progesterone in menopause. Combination HRT is often recommended as it decreases the amount of endometrial hyperplasia and cancer associated with unopposed estrogen therapy.
Some therapies include the use of androgens like testosterone or dehydroepiandrosterone DHEA as well. The Women's Health Initiative of the National Institutes of Health found disparate results for all cause mortality with RHT, finding it to be lower when HRT was begun earlier, between age , but higher when begun after age In older patients, there was an increased incidence of breast cancer , heart attacks and stroke , although a reduced incidence of colorectal cancer and bone fracture.
As a result of these findings, the number of women taking HRT dropped precipitously. The current indications for use from the U. Food and Drug Administration include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or urogenital atrophy, and prevention of osteoporosis. There have been a number of large-scale cross-sectional and cohort studies on the effects of HRT, the largest being in the United States, the United Kingdom and China.
Demographically, the vast majority of data available is in postmenopausal American women with concurrent pre-existing conditions, and with a mean age of over 60 years. That study looked at the effects of hormonal replacement therapy in postmenopausal women. Both age groups had a slightly higher incidence of breast cancer , and both heart attack and stroke were increased in older patients, although not in younger participants.
Treatment with unopposed estrogen the supplementation of endogenous estrogens without a progestogen is contraindicated if the uterus is still present, due to its proliferative effect on the endometrium. The WHI also found a reduced incidence of colorectal cancer when estrogen and progesterone were used together, and most importantly, a reduced incidence of bone fractures. Ultimately, the study found disparate results for all cause mortality with HRT, finding it to be lower when HRT was begun during ages 50—59, but higher when begun after age The data published by the WHI suggested supplemental estrogen increased risk of venous emboli and breast cancer but was protective against osteoporosis and colorectal cancer , while the impact on cardiovascular disease was mixed.
Genetic polymorphism appears to be associated with inter-individual variability in metabolic response to HRT in postmenopausal women.
These recommendations have not held up with further data analysis, however. Subsequent findings released by the WHI showed that all cause mortality was not dramatically different between the groups receiving conjugated equine estrogens CEEs , those receiving estrogen and progesterone, and those not on HRT at all. Specifically, the relative risk for all-cause mortality was 1. This would represent five fewer deaths per 1, women per 5 years of therapy. However, neither the WHI nor the Million Women Study differentiated the results for different types of progestogens used.
Medroxyprogesterone acetate MPA —the type most commonly used in the United States—was the only one examined by the WHI, which in its analysis and conclusions extrapolated the benefits versus risks of MPA to all synthetic progesterones. This conclusion has since been challenged by several researchers as unjustified and misleading, resulting in unreasonable, unnecessary avoidance by many women of HRT.
In fact, primate research indicates that the side effects of MPA may be much worse than those of other progestogens, and some human studies indicate that MPA may be responsible for negating the protective cardiac benefits of estrogen that were found for estrogen-only HRT users.
Critics including Bethea note that there are now research papers showing significantly better outcomes in brain, breast, and cardiovascular parameters with estradiol plus progesterone instead of MPA and conclude that further studies are needed to know more precisely what the differences in effects are when other progestins are used versus natural progesterone in HRT, so that women aren't needlessly discouraged from seeking HRT.
A robust Bayesian meta-analysis from 19 randomized clinical trials reported similar data with a RR of mortality of 0. The beneficial potential of HRT was bolstered in a consensus expert opinion published by The Endocrine Society , which stated that when taken during perimenopause or the initial years of menopause, hormonal therapy carries significantly fewer risks than previously published and reduces all cause mortality in most patient scenarios.
More recently developed forms of drug delivery include suppositories, subdermal implants, skin patches and gels. They have more local effect, lower doses, fewer side effects, and result in constant rather than cyclical serum hormone levels. The goal of HRT is to mitigate discomfort caused by diminished circulating estradiol and progesterone in menopause. In those with premature or surgically induced menopause, a combination HRT is often recommended, as it may also prolong life and may decrease a woman's chances of developing endometrial cancers associated with unopposed estrogen therapy, as well by decreasing the incidence of dementia.
Some recent therapies include the use of androgens as well. Data from numerous studies have consistently found that HRT leads to improvements in aspects of postmenopausal sexual dysfunction. The most prevalent of female sexual dysfunctions linked to menopause include lack of desire and low libido, both of which can be explained by changes in hormonal physiology.
Improvements in sexual pain, vaginal lubrication and orgasm are found to be statistically different from those using HRT.
Comparisons between orally administered pill and transdermal patch suggests that when estrogens are taken orally the risks of thrombophlebitis and pulmonary embolism are increased, an effect which is not seen with topical administration. Transdermal and transvaginal administration are not subject to first pass metabolism , and so lack the anabolic effects that oral therapy has on hepatic synthesis of Vitamin K dependent clotting factors.
The latter is associated with an increased incidence of venous clot. The impact of HRT on cardiovascular morbidity is a subject of much controversy in the medical literature. The reduced risk of cardiovascular diseases associated with HRT, reported in observational studies, has not been subsequently confirmed in randomized clinical trials. The increased risk of cardiovascular disease in the WHI was not statistically significant, and only found in the oldest women, and those who started HRT late after menopause began.
Women aged 50 to 59 using HRT showed a trend towards lower risk of coronary heart disease,  as did women who were within five years of the onset of menopause. A Cochrane review came to the result that in women starting HRT less than 10 years after menopause have a lower mortality and lower rate of coronary heart disease compared to placebo or no treatment, without any strong evidence of an effect on the risk of stroke.
Those starting therapy more than 10 years after menopause have little effect on mortality and coronary heart disease, but have an increased risk of stroke.
Overall, however, taking the increased risk of venous thromboembolism into account, it came to the conclusion that has HRT has little if any benefit for primary or secondary prevention of cardiovascular disease. The adverse cardiovascular outcomes may only apply to oral dosing with the progestin and equine estrogens in oral systemic therapy, while topical estradiol and estriol may not produce the same risks, due to the absence of anabolic effects of hepatic vitamin K dependent clotting factors.
On a molecular level, HRT at the time of menopause has effects on the lipid profile. Supplemental estrogen improves the lipid profile by reversing each of these effects. Beyond this, it improves cardiac contractility, coronary artery blood flow, metabolism of carbohydrates, and decreases platelet aggregation and plaque formation.
While combined estrogen-progesterone supplementation has been linked to an increased incidence of endometrial cancer, the specific subtype is usually stage I, or in situ , and has extremely low morbidity and mortality, and studies in American women have shown the tumor to not have propensity for growth into the myometrium or parametrial soft tissues.
When seen in the context of all cause mortality, women who take estrogen and develop endometrial cancer have higher survival rates than women who do not take hormonal therapy at all, which was due to the preventive effect of HRT on hip fractures.
Unopposed estrogen can also result in endometrial hyperplasia , a precursor to endometrial cancer. The extensive use of high-dose estrogens for birth control in the s is thought to have resulted in a significant increase in the incidence of this type of cancer. HRT is effective at reversing the effects of aging on muscle. According to a presentation at an American Academy of Neurology meeting,  HRT taken soon after menopause may help protect against dementia, but it raises the risk of mental decline in women who do not take HRT until they are older.
This suggests that there may be a "critical period" during which time taking HRT may have benefits, but if HRT is initiated after that period, it will not have such benefits and may cause harm. This is consistent with research that HRT improves executive and attention processes in postmenopausal women. This showed replacement treated compared to nontreated monkeys had long term improved prefrontal cortex executive abilities on the Wisconsin Card Sorting Test.
The relative risk RR of breast cancer varies from 1. A recent randomized controlled trial recently showed that increased breast cancer risk applied only to those women who take progesterone analogues, but not to those taking bio-identical progesterone itself, nor to hysterectomized women who take unopposed estrogen.
Some reports have not found an association of progesterone therapy and breast cancer. The absence of effect in these studies has been suggested to be due to selective prescription to overweight women, or to the very low progesterone serum levels after oral administration leading to a strong tumor inactivation rate.
For women who previously have had breast cancer, it is recommended to first consider non-hormonal options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators SERMs for steoporosis, cholesterol lowering agents and aspirin for cardiovascular disease and vaginal estrogen for local symptoms.
Observational studies of systemic HRT after breast cancer are generally reassuring. If HRT is necessary after breast cancer, estrogen only therapy or estrogen therapy with an intrauterine device with progestogen may be safer options than combined systemic therapy.
Estrogen prevents the activity of osteoclasts , and improves bone mineral density. Hip fracture is a leading cause of morbidity and mortality in older females, and usually does not occur in the setting of osteoporosis. Estrogen is the only medical therapy that has been shown to prevent hip fractures in women that are not osteoporotic, with efficacy superior to bisphosphonates or calcium and vitamin D supplementation.
A meta-analysis found that HRT was associated with an increased risk of ovarian cancer. The authors concluded that if this association is causal, women using HRT have about one additional case of ovarian cancer per 1, users. Prior studies were smaller, and many were of women who electively took hormonal therapy. One portion of the parallel studies followed over 16, women for an average of 5. The combination of hormones is referred to as Prempro. This WHI estrogen-plus-progestin trial was stopped prematurely in because preliminary results suggested risks of combined CEEs and progestins exceeded their benefits.
The first report on the halted WHI estrogen-plus-progestin study came out in July The study reported statistically significant increases in rates of breast cancer , coronary heart disease , strokes and pulmonary emboli. The study also found statistically significant decreases in rates of hip fracture and colorectal cancer.
The results were almost universally reported as risks and problems associated with HRT in general, rather than with Prempro, the specific proprietary combination of CEEs and progestins studied.
After the increased clotting found in the first WHI results was reported in , the number of Prempro prescriptions filled reduced by almost half. Following the WHI results, a large percentage of HRT users opted out of them, which was quickly followed by a sharp drop in breast cancer rates. The decrease in breast cancer rates has continued in subsequent years. The other portion of the parallel studies featured women who were post hysterectomy so who consequently did not need to take a progestin when using estrogen.
They were given either placebo or CEEs alone. This group did not show the risks demonstrated in the combination hormone study, and the estrogen-only study was not halted in However, in February it, too, was halted. The WHI trial was limited by low adherence, high attrition, inadequate power to detect risks for some outcomes, and evaluation of few regimens. Patients who were experiencing symptoms of the menopausal transition were excluded from the study, meaning that younger women who had only recently experienced menopause were not significantly represented.
As a result, while the average age of menopause is age 51, study participants were on average 62 years of age. Demographically, the vast majority were Caucasian, and tended to be slightly overweight and former smokers. Bioidentical hormone therapy BHT is the use of hormones that are chemically identical to those produced in a woman's body.
Others are provided in connection with the practices of pharmaceutical compounding and saliva testing to determine, and adjust, a woman's hormone levels. The latter two practices are not widely accepted in clinical medicine. Compounding has not demonstrated any benefits and presents risks of uncertain dosing, potency and possible contamination. In addition, saliva testing is of limited utility due to natural fluctuations in hormone levels, and lack of consensus for ideal dosage in humans.
The FDA has stated that BHT is unsupported by medical evidence, and its administration is considered false and misleading by the agency. The FDA has expressed concern that unfounded claims like these mislead women and health care professionals. Traditional therapy has been researched to quantify these risks and benefits, and are produced by manufacturers with stringent purity and potency standards.