Long term follow up of the WHI participants, however, has found no difference in all-cause , cardiovascular , or cancer mortality with HRT. The current indications for use from the United States Food and Drug Administration FDA include short-term treatment of menopausal symptoms , such as vasomotor hot flashes or vaginal atrophy , and prevention of osteoporosis. Approved uses of HRT in the United States include short-term treatment of menopausal symptoms such as hot flashes and vaginal atrophy, and prevention of osteoporosis.
A consensus expert opinion published by The Endocrine Society stated that when taken during perimenopause or the initial years of menopause, HRT carries fewer risks than previously published, and reduces all cause mortality in most scenarios. Women receiving this treatment are usually post- , peri- , or surgically menopausal. Menopause is the permanent cessation of menstruation resulting from loss of ovarian follicular activity, defined as beginning twelve months after the final natural menstrual cycle.
This twelve month time point divides menopause into early and late transition periods known as 'perimenopause' and 'postmenopause'. Successive analyses have found sometimes contradictory results, with the most recent publication in finding no difference for all cause mortality with HRT. HRT is often given as a short-term relief from menopausal symptoms during perimenopause. The most common of these are loss of sexual drive and vaginal dryness.
The effect of HRT in menopause appears to be divergent, with lower risk when started within five years, but no impact after ten. A Cochrane review suggested that women starting HRT less than 10 years after menopause had lower mortality and coronary heart disease , without any strong effect on the risk of stroke and pulmonary embolism.
Both therapies had an association with venous clots and pulmonary embolism. HRT also improves cholesterol levels. With menopause, HDL decreases, while LDL , triglycerides and lipoprotein a increase, patterns that reverse with estrogen. Beyond this, HRT improves heart contraction , coronary blood flow, sugar metabolism , and decreases platelet aggregation and plaque formation.
Effects of hormone replacement therapy on venous blood clot formation and potential for pulmonary embolism may vary with different estrogen and progestogen therapies, and with different doses or method of use.
What women should know about menopause | Society | The Guardian
Multiple studies suggest that the possibility of HRT related stroke is absent if therapy is started within five years of menopause,  and that the association is absent or even preventative when given by non-oral routes. In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. Endometrial cancer has been grouped into two forms in the context of hormone replacement.
Type 1 is the most common, can be associated with estrogen therapy, and is usually low grade. Type 2 is not related to estrogen stimulation and usually higher grade and poorer prognosis. Paradoxically, progestogens do promote the growth of uterine fibroids , and a pelvic ultrasound can be performed before beginning HRT to make sure there are no underlying uterine or endometrial lesions.
Studies regarding the association of breast cancer with hormone replacement have been mixed and vary with the type of replacement used; some evaluations suggest an increased risk, though in others it is decreased. There is a non-statistically significant increased rate of breast cancer for hormone replacement therapy with synthetic progesterone.
There have been no randomized controlled trials to date. The WHI also found a non-significant trend in the estrogen-alone clinical trial towards a reduced risk of breast cancer, though estrogen is usually only given alone in the setting of a hysterectomy due to the effect of unopposed estrogen on the uterus. HRT has been more strongly associated with risk of breast cancer in women with a lower range body mass indices BMIs. No breast cancer association has been found with BMIs of over For women who previously have had breast cancer, it is recommended to first consider other options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators SERMs for osteoporosis, 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 a progestogen may be safer options than combined systemic therapy. In the WHI, women who took combined estrogen-progesterone therapy had a lower risk of getting colorectal cancer.
However, the cancers they did have were more likely to have spread to lymph nodes or distant sites than colorectal cancer in women not taking hormones. A meta-analysis found that HRT was associated with an increased risk of ovarian cancer , with women using HRT having about one additional case of ovarian cancer per 1, users.
HRT can help with the lack of sexual desire and sexual dysfunction that can occur with menopause. For most women, the majority of change occurs during the late perimenopausal and postmenopausal stages.
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Testosterone, a hormone more commonly associated with males, is also present in women at a lower level. It peaks at age 30, but declines gradually with age, so there is little variation across the lifetime and during the menopausal transition. Not all women are responsive, especially those with preexisting sexual difficulties. Pain or discomfort with sex appears to be the most responsive component to estrogen. The effectiveness of hormone replacement can decline in some women after long-term use. In various placebo-controlled studies, improvements in vasomotor symptoms, emotional response, sleep disturbances, physical symptoms, and sexual desire have been observed.
HRT may increase risk of dementia if initiated after 65 years of age, but have a neutral outcome or be neuroprotective for those between 50—55 years. There is a decrease in hip fractures , which persists after the treatment is stopped, though to a lesser degree. Hormone replacement therapy in the form of estrogen and androgen can be effective at reversing the effects of aging on muscle.
Some common and uncommon side effects include: . The following are absolute and relative contraindications to HRT: . The extraction of CEEs from the urine of pregnant mares led to the marketing in of Premarin , one of the earlier forms of estrogen to be introduced.
Beginning in , studies began to show that without a progestogen, unopposed estrogen therapy with Premarin resulted in an 8-fold increased risk of endometrial cancer , eventually causing sales of Premarin to plummet. The Women's Health Initiative trials were conducted between and and were the first large, double-blind , placebo-controlled clinical trials of HRT in healthy women.
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Other risks include increased endometrial cancer , gallbladder disease, and urinary incontinence , while benefits include decreased hip fractures , decreased incidence of diabetes , and improvement of vasomotor symptoms. There also is an increased risk of dementia with HRT in women over 65, though when given earlier it appears to be neuroprotective. After the cessation of HRT, the WHI continued observe its participants, and found that most of these risks and benefits dissipated, though some elevation in breast cancer risk did persist. The arm of the WHI receiving combined estrogen and progestin therapy was closed prematurely in by its Data Monitoring Committee DMC due to perceived health risks, though this occurred a full year after the data suggesting increased risk became manifest.
In , the arm of the WHI in which post-hysterectomy patients were being treated with estrogen alone was also closed by the DMC. 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. 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 Initial data from the WHI in suggested mortality to be lower when HRT was begun earlier, between age 50 to 59, but higher when begun after age In older patients, there was an apparent increased incidence of breast cancer , heart attacks , venous thrombosis , and stroke , although a reduced incidence of colorectal cancer and bone fracture.
At the time, The WHI recommended that women with non-surgical menopause take the lowest feasible dose of HRT for the shortest possible time to minimize associated risks. As a result of these findings, the number of women taking HRT dropped precipitously. In when the first WHI follow up study was published, with HRT in post menopausal women, both older and younger 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.
Breast cancer was increased in women treated with estrogen and a progestin, but not with estrogen and progesterone or estrogen alone. Treatment with unopposed estrogen i. The WHI also found a reduced incidence of colorectal cancer when estrogen and a progestogen were used together, and most importantly, a reduced incidence of bone fractures.
Komen Perspectives - Managing Menopause (April 2012)
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 authors of the study recommended that women with non-surgical menopause take the lowest feasible dose of hormones for the shortest time to minimize risk. The data published by the WHI suggested supplemental estrogen increased risk of venous thromboembolism 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. 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 progestins. This conclusion has since been challenged by several researchers as unjustified and misleading, resulting in unreasonable, unnecessary avoidance by many women of HRT.
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In addition, subsequent findings released by the WHI showed that all cause mortality was not dramatically different between the groups receiving CEEs, those receiving estrogen and a progestogen, and those not on therapy. 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. The WHI 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 MPA 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 and so received either placebo progestogen 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. Several other large studies and meta-analyses have reported reduced mortality for HRT in women younger than age 60 or within 10 years of menopause, and a debatable or absent effect on mortality in women over Though research thus far has been substantial, further investigation is needed to fully understand differences in effect for different types of HRT and lengths of time since menopause.
There are five major human steroid hormones: estrogens, progestogens, androgens , mineralocorticoids , and glucocorticoids. Estrogens and progestogens are the two most often used in menopause. In women with intact uteruses , estrogens are almost always given in combination with progestogens, as long-term unopposed estrogen therapy is associated with a markedly increased risk of endometrial hyperplasia and endometrial cancer. There are many combined formulations which include both estrogen and progestogen. Specific types of hormone replacement include:  . A review of clinical research on tibolone — a synthetic medication — found it was more effective than placebo and less effective than combination hormone therapy in postmenopausal women, although it may cause bleeding, increase the risk of recurrent breast cancer in women with a history of breast cancer, and increase the risk of stroke in women over age 60 years.
Vaginal estrogen can improve local atrophy and dryness, with fewer systemic effects than estrogens delivered by other routes. Dosage is often varied cyclically to more closely mimic the ovarian hormone cycle, with estrogens taken daily and progestogens taken for about two weeks every month or every other month, a schedule referred to as 'cyclic' or 'sequentially combined'.
Alternatively, 'continuous combined' HRT can be given with a constant daily hormonal dosage. The medications used in menopausal HRT are available in numerous different formulations for use by a variety of different routes of administration :  . More recently developed forms of drug delivery are alleged to have increased local effect lower dosing, fewer side effects, and constant rather than cyclical serum hormone levels. This in turn prevents an increase in clotting factors and accumulation of anti-estrogenic metabolites, resulting in fewer adverse side effects, particularly with regard to cardiovascular disease and stroke.
Bioidentical hormone therapy BHT is the usage of hormones that are chemically identical to those produced in the body.