David Baxter PhD
Late Founder
Is Hormone Therapy Okay Again?
Berkeley Wellness
December 04, 2017
Many women hesitate to treat menopausal symptoms with hormone therapy, or avoid it altogether, because of concerns that were raised by findings from the landmark Women?s Health Initiative (WHI) trial on the hormones back in 2002. That clinical trial randomly assigned more than 27,000 women, ages 50 to 70, to receive either oral estrogen plus progestin, estrogen alone, or a placebo for an average of five to seven years.
Importantly, WHI researchers have continued to follow the participants?now for a total of 18 years?and have concluded that the use of hormone therapy is not associated with either increased or decreased mortality rates, according to their study, published in the Journal of the American Medical Association in September 2017.
That was true of the women who took estrogen plus progestin (the majority), as well as those taking estrogen alone. The latter group included only women who had a hysterectomy, because ?unopposed? estrogen increases the risk of uterine (endometrial) cancer in those who still have a uterus.
The new study focused on all-cause mortality as well as death rates from cardiovascular disease, all cancers, and other major illnesses (not the incidence of these diseases). All-cause mortality is a key measure of the ?net effect? of treatment on serious and life-threatening conditions, the researchers noted, since hormone therapy has such a complex pattern of potential risks and benefits.
Controversy and confusion
Menopausal hormone therapy has been difficult to evaluate because of its differing effects on the risk of various diseases. Such risks may depend on the age, health, and menopausal status of women, the formulation and dose of hormones, and the length of treatment. Its effects on various cancers are particularly complex.
Until WHI, hormone therapy was often promoted as a virtual ?fountain of youth? and specifically as a way to reduce the risk of heart disease (which, it turned out, it does not do) and to prevent bone loss and fractures (which it does). Buried in the avalanche of news reports about hormone therapy?s adverse effects in WHI was the fact that, during the five to seven years of treatment, death rates among the youngest women (those in their fifties) were lower in those taking hormones than in their counterparts taking a placebo.
The new study found that this benefit among the youngest women diminished subsequently and was no longer statistically significant after the total 18 years, except in the estrogen-only group, who continued to enjoy a longevity advantage.
Hormone treatment didn?t affect mortality rates among women in their sixties or seventies, either during treatment or in the long-term follow-up period.
?Compelling and reassuring?
After the initial WHI results were published 15 years ago, millions of women stopped hormone therapy or never started?including many who would have benefited from its effective treatment of hot flashes and other menopausal symptoms. Now that may change.
?These findings lend support to practice guidelines endorsing use of hormone therapy for recently menopausal women with moderate-to-severe symptoms, in the absence of contraindications,? the researchers concluded. However, the findings do not support the use of hormone therapy for the prevention of chronic diseases, they added, because of lack of evidence of benefit and lingering uncertainties about the risks. Similarly, in December 2017, the U.S. Preventive Services Task Force reaffirmed its recommendation that hormone therapy should not be used in an attempt to prevent chronic conditions, though hormone therapy remains a treatment option for menopausal symptoms.
These new data are ?compelling and reassuring,? according to the accompanying editorial, and ?hopefully will alleviate concerns that many patients and physicians have about the initiation of hormone therapy. For women with troubling vasomotor symptoms [that is, hot flashes and night sweats], premature menopause, or early-onset osteoporosis, hormone therapy appears to be both safe and efficacious.?
Two things to keep in mind:
First, compared to the hormones used in the WHI trial, lower doses and different formulations and modes of administration (such as transdermal patches, gels, and sprays) are commonly used today, and these will require additional long-term testing, the WHI researchers noted. Presumably the lower doses and other modes of administration are just as safe?or safer.
A British analysis
in the journal BJOG in September 2017 looked at 47 clinical trials on therapies for menopausal vasomotor symptoms and concluded that transdermal estrogen/progestin patches are most effective for women who have not had a hysterectomy. It did not evaluate adverse effects, however.
Second, for women who have had their uterus removed, estrogen alone has a better risk/benefit ratio than estrogen plus progestin. But women who have not had a hysterectomy cannot opt for estrogen alone because it can cause uterine cancer, as was discovered in the 1960s and 1970s, before progestin was added in order to counter this risk.
Latest Hormone Therapy Advice from NAMS
Here?s a summary of advice from the 2017 position statement on hormone therapy of the North American Menopause Society (NAMS), which appeared in the journal Menopause in July:
Unless contraindicated (see below), for the treatment of menopausal symptoms such as hot flashes, the sooner after the onset of menopause a woman starts hormone therapy, the lower her risk of adverse events such as stroke and blood clots. Conversely, the longer a woman waits, the greater the risks.
The point at which these risks outweigh the potential benefits of hormone therapy varies considerably, depending on variables such as a woman?s risk factors for cancer and cardiovascular disease, her medical history, and the severity of her menopausal symptoms, but this point is generally reached somewhere between 10 and 20 years after the onset of menopause or between ages 60 and 70, whichever occurs first.
Because of the considerable individual variability in when the critical point is reached, a woman considering hormone therapy should discuss her risk/benefit profile with her health care provider. ?Treatment should be individualized to identify the most appropriate hormone therapy type, dose, formulation, route of administration, and duration of use,? according to the statement.
Contraindications for hormone therapy include unexplained vaginal bleeding, coronary heart disease, stroke, thromboembolic disease, and certain types of breast and uterine cancers. Your health care provider will review your medical and family history to make sure you don?t have these or any other contraindications before starting hormone therapy.
For genital and urinary symptoms not relieved with over-the-counter or other therapies, low-dose vaginal estrogen therapy is recommended.
Also see Is Vaginal Estrogen Safe?
Berkeley Wellness
December 04, 2017
Many women hesitate to treat menopausal symptoms with hormone therapy, or avoid it altogether, because of concerns that were raised by findings from the landmark Women?s Health Initiative (WHI) trial on the hormones back in 2002. That clinical trial randomly assigned more than 27,000 women, ages 50 to 70, to receive either oral estrogen plus progestin, estrogen alone, or a placebo for an average of five to seven years.
Importantly, WHI researchers have continued to follow the participants?now for a total of 18 years?and have concluded that the use of hormone therapy is not associated with either increased or decreased mortality rates, according to their study, published in the Journal of the American Medical Association in September 2017.
That was true of the women who took estrogen plus progestin (the majority), as well as those taking estrogen alone. The latter group included only women who had a hysterectomy, because ?unopposed? estrogen increases the risk of uterine (endometrial) cancer in those who still have a uterus.
The new study focused on all-cause mortality as well as death rates from cardiovascular disease, all cancers, and other major illnesses (not the incidence of these diseases). All-cause mortality is a key measure of the ?net effect? of treatment on serious and life-threatening conditions, the researchers noted, since hormone therapy has such a complex pattern of potential risks and benefits.
Controversy and confusion
Menopausal hormone therapy has been difficult to evaluate because of its differing effects on the risk of various diseases. Such risks may depend on the age, health, and menopausal status of women, the formulation and dose of hormones, and the length of treatment. Its effects on various cancers are particularly complex.
Until WHI, hormone therapy was often promoted as a virtual ?fountain of youth? and specifically as a way to reduce the risk of heart disease (which, it turned out, it does not do) and to prevent bone loss and fractures (which it does). Buried in the avalanche of news reports about hormone therapy?s adverse effects in WHI was the fact that, during the five to seven years of treatment, death rates among the youngest women (those in their fifties) were lower in those taking hormones than in their counterparts taking a placebo.
The new study found that this benefit among the youngest women diminished subsequently and was no longer statistically significant after the total 18 years, except in the estrogen-only group, who continued to enjoy a longevity advantage.
Hormone treatment didn?t affect mortality rates among women in their sixties or seventies, either during treatment or in the long-term follow-up period.
?Compelling and reassuring?
After the initial WHI results were published 15 years ago, millions of women stopped hormone therapy or never started?including many who would have benefited from its effective treatment of hot flashes and other menopausal symptoms. Now that may change.
?These findings lend support to practice guidelines endorsing use of hormone therapy for recently menopausal women with moderate-to-severe symptoms, in the absence of contraindications,? the researchers concluded. However, the findings do not support the use of hormone therapy for the prevention of chronic diseases, they added, because of lack of evidence of benefit and lingering uncertainties about the risks. Similarly, in December 2017, the U.S. Preventive Services Task Force reaffirmed its recommendation that hormone therapy should not be used in an attempt to prevent chronic conditions, though hormone therapy remains a treatment option for menopausal symptoms.
These new data are ?compelling and reassuring,? according to the accompanying editorial, and ?hopefully will alleviate concerns that many patients and physicians have about the initiation of hormone therapy. For women with troubling vasomotor symptoms [that is, hot flashes and night sweats], premature menopause, or early-onset osteoporosis, hormone therapy appears to be both safe and efficacious.?
Two things to keep in mind:
First, compared to the hormones used in the WHI trial, lower doses and different formulations and modes of administration (such as transdermal patches, gels, and sprays) are commonly used today, and these will require additional long-term testing, the WHI researchers noted. Presumably the lower doses and other modes of administration are just as safe?or safer.
A British analysis
in the journal BJOG in September 2017 looked at 47 clinical trials on therapies for menopausal vasomotor symptoms and concluded that transdermal estrogen/progestin patches are most effective for women who have not had a hysterectomy. It did not evaluate adverse effects, however.Second, for women who have had their uterus removed, estrogen alone has a better risk/benefit ratio than estrogen plus progestin. But women who have not had a hysterectomy cannot opt for estrogen alone because it can cause uterine cancer, as was discovered in the 1960s and 1970s, before progestin was added in order to counter this risk.
Latest Hormone Therapy Advice from NAMS
Here?s a summary of advice from the 2017 position statement on hormone therapy of the North American Menopause Society (NAMS), which appeared in the journal Menopause in July:
Unless contraindicated (see below), for the treatment of menopausal symptoms such as hot flashes, the sooner after the onset of menopause a woman starts hormone therapy, the lower her risk of adverse events such as stroke and blood clots. Conversely, the longer a woman waits, the greater the risks.
The point at which these risks outweigh the potential benefits of hormone therapy varies considerably, depending on variables such as a woman?s risk factors for cancer and cardiovascular disease, her medical history, and the severity of her menopausal symptoms, but this point is generally reached somewhere between 10 and 20 years after the onset of menopause or between ages 60 and 70, whichever occurs first.
Because of the considerable individual variability in when the critical point is reached, a woman considering hormone therapy should discuss her risk/benefit profile with her health care provider. ?Treatment should be individualized to identify the most appropriate hormone therapy type, dose, formulation, route of administration, and duration of use,? according to the statement.
Contraindications for hormone therapy include unexplained vaginal bleeding, coronary heart disease, stroke, thromboembolic disease, and certain types of breast and uterine cancers. Your health care provider will review your medical and family history to make sure you don?t have these or any other contraindications before starting hormone therapy.
For genital and urinary symptoms not relieved with over-the-counter or other therapies, low-dose vaginal estrogen therapy is recommended.
Also see Is Vaginal Estrogen Safe?
