10x10: Dr Northrup's Top 10 Women's Health Findings: 2000-2010

 

Dr. Christiane Northrup MD is a mentor of mine. She is a pioneering gynecologist who attunes to women's wisdom underlying the issues we face. She caught my attention on PBS when I was in college with her focus on empowering women during surgery to get regional anesthesia, so they could be awake during a hysterectomy and participate in the decision-making, rather than anesthestetized objects on a table.

Here is a link to Dr. Christiane Northrup's top 10 findings in Women's Health over the past decade, complete with details. A summary:

1. End of One-Size Fits-All Hormone Therapy
2. Fetal Monitoring Doesn’t Improve Pregnancy Outcomes
3. Early Detection of Breast Cancer is an Imperfect Solution
4. Fish Oil Proven Protective Beyond a Shadow of a Doubt 
5. Optimal Vitamin D Level is Critical for Robust Health
6. Stem Cells Discovered in Menstrual Blood
7. Natural Progesterone Holds Great Promise for Heart Health
8. Iodine Reduces Breast Pain
9. Breast is Still Best
10. Educating Girls is the Key to Planetary Health

Hormone Therapy: Continuous Progesterone Safer

Which is better: to take progesterone continuously or sequentially (e.g., day 12-26 each month)? There are arguments on both sides, but this latest study shows that continuous progesterone has a 76% lower risk of endometrial cancer after 3-5 years. That is why I recommend regular uterine monitoring every 6+ months in women on sequential progesterone. -- SG

The long-term safety of different hormone therapy regimens has not been adequately studied in the context of endometrial cancer risk. In a national cohort study, investigators followed 224,000 Finnish women (age, >50) who used oral or transdermal estrogen-progestin (E+P) HT from 1994 to 2006. HT regimens were considered to be sequential if daily estradiol was accompanied by 10 to 14 days of progestin monthly or, in long-cycle regimens, during each 3-month interval. In continuous regimens, both estradiol and progestin were used nonstop. Incidence of endometrial cancer in E+P users was compared with that in all Finnish women.

A total of 1402 cases of incident endometrial cancer were identified. Compared with the general population, E+P users overall had 54% and 23% higher relative risk for type I and type II endometrial tumors, respectively. Monthly sequential E+P HT was associated with 69% (5 years' use) and 156% (10 years' use) higher risk for type I tumors. At 5 and 10 years of use, long-cycle sequential HT was associated with substantially higher risk for type I tumors than was monthly sequential HT. The endometrial safety of transdermal and oral sequential HT was similar; sequential HT with medroxyprogesterone acetate and norethindrone acetate also exhibited similar endometrial safety. Use of continuous E+P HT was associated with lower risk for type I tumors than in the overall population (76% risk reduction after 3–5 years' use).

Comment: Unopposed estrogen therapy or E+P hormone therapy with inadequate progestin raises risk for low-grade endometrial adenocarcinoma (i.e., type I) in menopausal women. Risks for high-grade serous papillary carcinoma and clear-cell adenocarcinoma (i.e., type II) are less clearly associated with HT use. These results are important in clarifying that, although long-term continuous E+P HT is protective, sequential therapy substantially raises risk for endometrial adenocarcinoma. The authors estimate that among 1000 women who use E+P HT for 10 years, eight additional cancer cases will be diagnosed if HT is sequential and monthly, whereas three to four fewer cases will be diagnosed if HT is continuous. For women who use sequential E+P HT long term, endometrial monitoring is appropriate.
— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health December 17, 2009

Citation(s):
Jaakkola S et al. Endometrial cancer in postmenopausal women using estradiol–progestin therapy. Obstet Gynecol 2009 Dec; 114:1197.

No Increase in Breast Cancer Risk in BRCA1 Carriers on HT

Can you tell I'm catching up on my journal reading? I've got several patients with the "breast cancer gene" or have a high risk for it (2 or more relatives with breast cancer), so this latest data showing no increased risk of breast cancer in BRCA1 carriers on Hormone Therapy is GOOD NEWS.

Also from North American Menopause Society.


Eisen A, Lubinski J, Gronwald J, et al, and the Hereditary
Breast Cancer Clinical Study Group. Hormone therapy and
the risk of breast cancer in BRCA1 mutation carriers. J Natl
Cancer Inst 2008;100:1361-1367. Level of evidence: II-2.

Using hormone therapy (HT) is not associated
with an increased risk for breast cancer in
postmenopausal women with a BRCA1 mutation,
this study suggests. In fact, researchers found a
decreased risk with HT use among this small
cohort with the mutation. Participants were
drawn from the larger cohort of the Hereditary
Breast Cancer Clinical Study, a prospective study
to evaluate nongenetic modifiers of cancer risk in
BRCA1 and BRCA2 mutation carriers. Cases
were diagnosed with invasive breast cancer after
reaching menopause. Controls had experienced
menopause and did not have breast cancer. Cases
and controls were matched for year of birth, age
at menopause, and type of menopause; 236
matched sets with the BRCA1 mutation were
generated. A questionnaire administered to each
woman garnered information on medical and
reproductive history and past and current HT use
(average age, 58.2 y; range, 32-85 y). The study
analyzed whether HT use after surgical or natural
menopause is associated with subsequent risk for
breast cancer in women with BRCA1 mutation.

More controls than cases had used HT (29% vs.
20%); the average duration was 3.7 years for
controls and 4.0 years for cases. Compared with
never use, women who had used HT had a
lower risk of breast cancer (odds ratio [OR],
0.58; 95% confidence interval [CI], 0.35-0.96;
P = 0.03). There was no modification of the OR
for duration of use, and the association was
similar for current and past users. Results were
also similar for women who had undergone
surgical as opposed to natural menopause. For
women who used estrogen only, there was an
inverse association with breast cancer risk (OR,
0.51; 95% CI, 0.27-0.98; P = 0.04). Results
were similar with combined estrogen and
progestogen (OR, 0.66; 95% CI, 0.34-1.27; P =
0.21). Surprisingly, HT use was reported for
12% of patients with estrogen-receptor positive
(ER+) tumors but only 23% of women with
estrogen-receptor negative (ER-) tumors. ER
status was available in 44% of cases.

Comment. There is a growing body of
evidence suggesting that the premature loss of
ovarian function caused by bilateral
oophorectomy performed before natural
menopause is associated with several negative
outcomes including an increased risk of
premature death, cardiovascular disease,
cognitive impairment or dementia,
parkinsonism, osteoporosis and bone fractures,
decline in psychological well-being, and
decline in sexual function. HT use may prevent
some but not all of these negative outcomes.
After receiving a positive genetic test result,
68% of women in the United States and 54% of
women in Canada with a BRCA1 or BRCA2
mutation undergo oophorectomy.1 The surgery
has been associated with risk reductions of 50%
or more for breast cancer and of 80% for
ovarian or peritoneal cancer. Some women
might be reluctant to undergo premenopausal
oophorectomy because of the adverse effects of
surgical menopause and are concerned that if
HT were taken to alleviate symptoms, then
their risk of breast cancer might rise.

The majority of BRCA1-associated breast
cancers in the current study (68%) were ER-. If
the adverse effect of HT were limited to ER+
cancers, then we would not expect to see an
acute effect of similar magnitude in mutation
carriers. It may be also that HT use protects
against the early stages of cancer development,
which results in a decline in the incidence of
breast cancer later in life. Published studies show
that in the noncarrier population, the increased
breast cancer risk associated with HT appears to
be stronger for ER+ cancers than ER-.2 If HT
were a risk factor for ER+ breast cancer in
BRCA1 mutation carriers as well, one would
expect that a greater proportion of women with
ER+ breast cancers had used HT than women
with ER- breast cancers. This was not seen, and
these findings suggest that the use of menopausal
HT is not associated with an increase in the risk
of breast cancer among women with a BRCA1
mutation, but the numbers of cases known to be
ER+ are too small to draw a definite conclusion.

It may be also that HT use protects against the
early stages of cancer development, which results
in a decline in the incidence of breast cancer later
in life. If HT promotes the growth of existing
ER+ breast cancers but protects against the early
stages of development of new breast cancers
(ER+ and ER-), then we would expect HT to
protect against breast cancer in BRCA1 mutation
carriers (who are mostly ER-).

Editorial writers have argued that the results
presented by Eisen et al regarding HT use in
postmenopausal BRCA1 mutation carriers
provide some evidence for safety but are
insufficient to reliably inform routine clinical
practice.3 Decision making regarding menopausal
HT in women at increased risk of breast cancer is
complex. The current HT package insert
identifies climacteric symptoms as the main
indication of HT use at the lowest dose and
shortest duration consistent with therapeutic
goals. We do not know how many post-
menopausal women with BRCA1 mutations have
limiting symptoms of hot flashes, vaginal/vulvar
problems, and/or sexual dysfunction that
cannot be addressed using nonhormonal
approaches, nor do we know how to define the
term “limiting” as a threshold for HT use.

Eisen et al say that it is not possible to
recommend an optimal duration of HT, but some
experts (eg, the National Comprehensive
Cancer Network) have suggested that “short-
term hormone replacement therapy” be
prescribed until the time of natural menopause
(ie, age 50-54).4 After that age, consideration
should be given to the use of tamoxifen for
breast cancer risk reduction. In mathematical
models, prophylactic oophorectomy lengthens
life expectancy in women with BRCA1/2
mutations, irrespective of whether HT is used
after oophorectomy. Women with BRCA1/2
mutations who undergo prophylactic
oophorectomy after completion of childbearing
should decide about short-term HT based
largely on quality-of-life issues rather than life
expectancy, and consider discontinuing
treatment at the time of expected natural
menopause, approximately age 51.

Victor G. Vogel, MD, MHS
Associate Investigator
Magee-Womens Research Institute
Professor, Medicine and Epidemiology
University of Pittsburgh
Co-Director, University of Pittsburgh Cancer
Institute Biochemoprevention Program
Director, UPCI/Magee-Womens Hospital Breast
Cancer Prevention Program

References
1. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, et al.
International variation in rates of uptake of preventive
options in BRCA1 and BRCA2 mutation carriers. Int J
Cancer 2008;122:2017-2022.
2. Ravdin PM, Cronin KA, Howlader N, et al. The
decrease in breast-cancer incidence in 2003 in the
United States. N Engl J Med 2007;356:1670-1674.
3. Chlebowski RT, Prentice RL. Menopausal hormone
therapy in BRCA1 mutation carriers: uncertainty and
caution. J Natl Cancer Inst 2008;100:1341-1343.
4. National Comprehensive Cancer Network. NCCN
Clinical Practice Guidelines in Oncology. Genetic/
Familial High-Risk Assessment: Breast and Ovarian.
Available at http://www.nccn.org/professionals/
physician_gls/PDF/genetics_screening.pdf. Accessed
December 10, 2008.

Hormone Therapy Lowers Colon Cancer 25-36%

Here's another post from North American Menopause Society. Seems cyclic progesterone was associated with the greatest risk reduction of colon cancer. Check it out.

Does hormone therapy decrease colorectal cancer risk?

Johnson JR, Lacey JV Jr, Lazovich D, et al. Menopausal
hormone therapy and risk of colorectal cancer. Cancer
Epidemiol Biomarkers Prev 2009;18:196-203.

We evaluated colorectal cancer risk associated
with the duration and recency of specific
menopausal hormone therapy formulations (ie,
unopposed estrogen versus estrogen plus
progestin) and regimens (ie, sequential versus
continuous estrogen plus progestin use) among
56,733 postmenopausal women participating in
the Breast Cancer Detection Demonstration
Project follow-up study. Hormone therapy use
and other risk factors were ascertained through
telephone interviews and mailed questionnaires
from 1979 to 1998. The final cancer group
included 960 women who were identified from
self-report, medical records, state registry data,
and the National Death Index. Poisson regression
was used to generate multivariable rate ratios
(RR) and 95% confidence intervals (95% CI).
We observed a decreased risk of colorectal
cancer among ever users of unopposed estrogen
therapy (RR, 0.83; 95% CI, 0.70-0.99). Among
estrogen users, the largest reduced risk was
observed for current users (RR, 0.75; 95% CI,
0.54-1.05) and users of ≥ten years duration
(RR, 0.74; 95% CI, 0.56-0.96). We found a
reduced risk among users of estrogen plus
progestin therapy (RR, 0.78; 95% CI, 0.60-
1.02), with sequential regimen users (progestin
<15 days per cycle) having the largest risk
reduction (RR, 0.64; 95% CI, 0.43-0.95). Past
users of ≥5 years ago (RR, 0.55; 95% CI, 0.32-
0.98) had the largest risk reduction. In this
study, estrogen plus progestin use, especially
sequential regimen use, was associated with the
largest overall reduction of colorectal cancer
risk.

Comment. This is a retrospective study, the
stated purpose of which was to identify
separate risk estimates for colon cancer
according to menopausal hormone form-
ulations. A paper published 9 years earlier1
from the same database found a suggested
inverse relationship between the use of HT and
colon cancer. The current paper analyzed
postmenopausal women divided into groups of
never users, those who had ever used estrogen,
and those who had ever used estrogen plus
progestogen (EPT), and then further divided
them by sequential hormone use and length of
time exposed to HT. What the current authors
found was that those who had ever used
unopposed estrogen had a decreased risk of
colon cancer. Those who had used sequential
EPT had the largest risk reduction. What does
this information add to our knowledge of this
topic?

Estrogen receptors have been detected on colonic
cells, with estrogen-receptor β being over-
expressed in healthy colon cells and reduced in
colon cancer cells. This overexpression, coupled
with negligible expression of estrogen-receptor α,
is thought to provide protection by HT against
colon cancer. What is also known is that
prescribing patterns for HT vary among race,
with African-American, Asian, and Latina
women receiving less treatment than Caucasian
women. An evaluation of how many women
were represented in each group rather than a
designation of “nonwhite” and a designation of
“person-years” only would have been
informative. It would also have been beneficial if
the groups had been matched by age, ethnicity,
and HT use (perhaps this is a paper that will be
published later).

African-American women have the highest risk
for colon cancer, higher even than white males;
and colon cancer in these women is often
detected at a more advanced stage. If HT really
does reduce the risk of colon cancer, all women
should have a discussion with their healthcare
provider about the potential benefits of HT for
them. A prospective study of matched groups of
women would be very informative regarding risk
reduction across ethnic groups in which there is a
dearth of comparative information available.
Women who use HT are more likely to have
mammograms, as well as Pap smears and
colonoscopies. Colonoscopy, however, is still at
the bottom of the list even for women who
regularly undergo other types of health screening.
It would be helpful if healthcare providers
encouraged women to have a colonoscopy. It has
been shown that if a healthcare provider strongly
recommends a test, a patient will often agree.

As March is National Colon Cancer Awareness
Month, this might be a good time to consider a
large-scale prospective randomized trial of HT
use with timed colon cancer screening across
ethnic groups by those in this field.
Michelle Inkster, MD, PhD
Department of Gastroenterology and Hepatology
Cleveland Clinic
Cleveland, OH

Reference:
1. Troisi R, Schairer C, Chow WH, et al. A prospective
study of menopausal hormones and risk of colorectal
cancer (United States). Cancer Causes Control 1997;

Hormone Imbalance: Symptoms

After many requests, I am re-posting this from my other blog as it is consistently the most popular and my patients seem  to love it. It does not include enough questions related to leptin- and insulin-resistance... more on this in future blogs.

-- SG

How do you know if your hormones are out of balance? I combine a careful history of what my patients are experiencing, their nutritional status, level of activity/lifestyle and sleep along with symptom questionnaires and testing. If any part is left out, we may miss the root cause of the hormone imbalance.  Dr. John Lee's books are helpful with understanding symptoms, and I will provide those below with some modifications I've made.  If you are taking the questionnaire, check off any symptoms that you experience from each symptom group, then we'll integrate at the end.

Symptom Group 1: 

PMS?

Anxiety?

Cyclical headaches (menstrual or hormonal migraine)?

Insomnia?

Early miscarriage?

Lumpy or painful breasts?

Infertility?

Symptom Group 2:

Vaginal dryness or irritation?

Painful sex?

Bladder infections?

Night sweats

Hot flashes

Poor memory?

Depression, especially with lethargy?

Low libido?

Symptom Group 3:

Bloating and/or puffiness?

Abnormal paps?

Rapid weight gain?

Breast tenderness?

Mood swings?

Heavy bleeding?

Depression with anxiety?

Migraines?

Insomnia?

Brain fog?

Red flush on face?

Gallbladder problems?

Weepiness?

Symptom Group 4:

Number of checked symptoms for Group 1 & 3 combined

Symptom Group 5:

Acne?

Polycystic Ovary Syndrome?

Excess hair on face/chest/or arms?

Hyper- or hypo-glycemia and/or unstable blood sugar?

Thinning head hair?

Infertility?

Ovarian cysts?

Midcycle pain?

Symptom Group 6:

Low libido?

Debilitating fatigue?

Unstable blood sugar?

Brain fog?

Low blood pressure?

Thin or dry skin?

Intolerance to exercise?

Brown spots on skin?

For assessment, tally the total number of symptoms in each category.  If you have 2 or more symptoms from a grouping - you may have the following diagnosis. I recommend you sort this out with an integrative physician.

Group 1:  Progesterone deficiency.  This is the most common hormone imbalance of all ages.  Best approaches are to optimize diet, reduce synthetic hormones if you are taking any (including birth control pills) and add bioidentical progesterone if appropriate.

Group 2:  Estrogen deficiency.  This is most common in menopausal women, especially skinny minnies.  Dietary changes and herbal therapies are often helpful as a first approach.

Group 3:  Excess estrogen. We see excess estrogen when women are taking synthetic estrogen, too much bioidentical estrogen (estradiol, estriol, tri-est), or are exposed to environmental xenoestrogens.  Xenoestrogens refer to the 700+ chemicals in the environment that act like endrocrine disruptors in the body, usually by binding the estradiol receptor.  Xenoestrogens have estrogen-like effects such as fertilizers, pesticides and lauryl sulfates.

Group 4:  Estrogen dominance.  Usually caused by not having sufficient progesterone to balance estrogen.  Causes vary from not enough progesterone to too much estrogen, or as is common in premenopause (age 35-50):  low estrogen but superlow progesterone.

Group 5: Excess androgens or male hormones.  Often this is caused by insulin and/or leptin resistance, and we can reverse this with dietary changes and supplements, but other approaches are effective as well.

Group 6:  Cortisol excess or deficiency.  Most people need a laboratory test to differentiate.  This is caused by adrenal fatigue which results from chronic stress.

I find very few women survive work and kids without some degree of adrenal fatigue.

There also is interdependence among these different hormonal systems with each other as well as with neurotransmitters.  For instance, estrogen acts like a selective serotonin reuptake inhibitor and helps mood in many women.  Also, if adrenal hormones are off, this can interfere with conversion of T4 (inactive thyroid hormone) to T3 (active form of thyroid hormone).

For all of these conditions or for further information, I recommend consulting an integrative physician in your area such as those in this database.

Revisiting Hormone Therapy in Women

Happy Holidays. Here is a nice summary of the latest view, albeit conventional, from the Harvard Women's Health Watch, Dec 2007. SG

Harvard Women's Health Watch | December 2007

Revisiting hormone therapy’s risks and benefits

A more nuanced picture may emerge as researchers re-examine data from the government’s massive postmenopausal hormone trials.

Hormone therapy has long been the standard treatment for relieving menopausal symptoms: hot flashes, night sweats, and vaginal dryness. Until 2002, many clinicians were also recommending it long term to prevent chronic health problems, including heart disease, stroke, and osteoporosis. There was some evidence that estrogen might contribute to breast cancer, but except for women at especially high risk for that disease, cardiovascular disease was a more serious concern — a far greater cause of death and disability. For that reason, most health organizations recommended that postmenopausal women consider taking hormone therapy.

Then, in 2002, the hormonal approach to averting women’s later-life ills screeched to a halt. Researchers had to stop the Women’s Health Initiative (WHI) randomized trial of estrogen and progestin (in the form of Prempro) because the hormone combination was actually causing more heart attacks and strokes than a placebo, as well as more blood clots and breast cancer.

Two years later, the WHI’s trial of estrogen alone (Premarin), also ended early, after it became apparent that estrogen increased the rate of strokes and blood clots without conferring any benefits on the heart.

Although there were some benefits — fewer fractures in both trials and a reduced risk for colon cancer in the combined-hormone trial — they didn’t outweigh the risks. That left hormone therapy back where it started, as a short-term treatment for menopausal symptoms.

Impact and critique of the WHI

Hormone therapy is still the most effective treatment for hot flashes and night sweats. But the WHI results — and the associated media firestorm — left women worried and confused about even such short-term use. They were told to use hormones only for short periods and at low doses, and hormone therapy prescriptions plummeted. (One study reported a 75% drop between 2002 and 2006.) Yet menopausal women looking for symptom relief shouldn’t misinterpret the WHI findings. These studies were not about short-term management of menopausal symptoms. Moreover, the results aren’t above criticism. New questions have arisen as scientists try to reconcile the findings of earlier observational studies with those of the WHI — a randomized, placebo-controlled trial, considered the “gold standard” type of clinical investigation.

Some critics argue that the WHI results may not apply to the typical woman considering hormone therapy because most of the 27,347 participants were in their 60s and 70s — well past the perimenopausal transition and early menopause (the usual time for starting hormone therapy). Others say that the risks were overstated. Each year, for example, the women taking Prempro had only six more heart attacks per 10,000 than the women taking a placebo; among younger women, the difference was even less.

Because of these and other concerns, scientists have been re-examining the WHI data and undertaking new trials. Researchers are also reappraising earlier studies that suggested hormone therapy could prevent cardiovascular disease.

Some scientists now suggest that the cardiac risk and benefit of hormone therapy may depend on a woman’s age, particularly the age at which she starts taking hormones. This new hypothesis doesn’t change current recommendations (see chart), but it may reassure perimenopausal and newly menopausal women who are considering short-term hormone treatment for symptom relief.

Recommendations regarding hormone therapy (HT)* use

Organization

Conclusions/recommendations

U.S. Preventive Services Task Force (USPSTF)**

Recommends against the routine use of HT to prevent chronic conditions in postmenopausal women.

North American Menopause Society

Moderate to severe vasomotor symptoms (hot flashes and night sweats) are the main use for systemic HT.

Food and Drug Administration

HT should be used at the lowest dose and for the shortest time needed to reach treatment goals, although it’s not known how low you should go to reduce the risk of serious side effects. When hormone therapy is prescribed only for vaginal symptoms, consider topical vaginal products.

American College of Obstetricians and Gynecologists

Estrogens are the most effective treatment for menopausal vasomotor symptoms (hot flashes and night sweats). Their use (with or without a progestin) should be reassessed yearly. The lowest effective dose should be used for the shortest possible time to alleviate symptoms.

American Society for Reproductive Medicine

Low-dose estrogen is a valid option for many seeking short-term relief from menopausal symptoms. HT does not provide additional health benefits that would justify its use beyond the immediate relief of menopausal symptoms. HT is not indicated for the primary or secondary prevention of coronary artery disease events.

Canadian Task Force on Preventive Health Care

HT should not be used for the primary prevention of chronic diseases in postmenopausal women. To maintain heart health, women should use other preventive strategies, such as increased exercise, smoking cessation, and blood pressure control. There’s not enough evidence to make a recommendation on HT regarding stroke and death from stroke.

*HT refers to estrogen alone, or estrogen plus a progestin.

**The USPSTF did not consider the use of hormone therapy for managing menopausal symptoms.

Heart risk: Is it a matter of timing?

The lack of heart benefits in the WHI contradicts findings from observational studies, such as the Nurses’ Health Study, in which participants are followed for years but are not asked to take medications or do anything differently. In those studies, women have tended to start taking hormones closer to the onset of menopause. Researchers have observed that these women suffer fewer of the heart problems caused by atherosclerosis (for example, angina and heart attacks) than women who don’t take hormones.

The idea that hormone therapy might help protect women from atherosclerosis was biologically plausible. It’s long been recognized that women develop atherosclerosis-related heart problems at an older age than men — that is, after menopause and the decline in estrogen. And in animal studies, estrogen has been shown to slow the development of atherosclerosis.

So why might estrogen then increase the risk of heart disease in women who start taking it at an older age? Evidence indicates that estrogen can destabilize atherosclerotic plaques, the artery-clogging accumulations of cholesterol and debris that are a major source of heart disease. Estrogen appears to make plaques more vulnerable to rupture, which can result in a heart attack. Older women are more likely to have developed plaques. So for them, estrogen might do more harm than good. It may be that hormone therapy is good for the heart only during a fairly narrow window, when plaques are starting to form but are not fully developed.

Nurses’ Health Study researchers found some support for this hypothesis in 2006 in a study undertaken to shed light on the discrepancies between the WHI results and earlier research. They found a 30% reduction in risk for heart disease among women who began hormone therapy within about four years of menopause, but little or no cardiac benefit for women who started hormones either after age 60 or 10 or more years after menopause.

A reanalysis of the WHI data turned up similar evidence that timing may be a factor. Investigators reporting in the Journal of the American Medical Association (April 4, 2007) found no increased risk for heart disease among hormone users ages 50 to 59 and a suggestion of reduced risk among women who started hormone therapy within 10 years after menopause. Thereafter, the greater the gap between onset of menopause and start of hormone therapy, the greater the risk for heart disease, especially in those with a history of hot flashes and night sweats. Stroke remained a problem, regardless of time since menopause, for women receiving either estrogen alone or combined therapy. The risk for breast cancer rose after five years in women taking combined hormones, although not in those taking estrogen alone.

In an ancillary study, WHI investigators assessed coronary artery calcium, which is a marker for atherosclerosis, in 1,064 women ages 50 to 59 who’d had a hysterectomy before entering the WHI estrogen-only trial. The women took their study medications for an average of 7.4 years and then, a year after the trial ended, they underwent CT scans of the heart. Results, published in the June 21, 2007, issue of The New England Journal of Medicine, showed that the estrogen-takers had less calcified plaque in their arteries than the placebo takers, suggesting a reduced risk for future cardiovascular events. But it’s not known how long this benefit would have lasted — or whether it would have actually led to fewer heart attacks or strokes — if the women had continued taking estrogen. According to WHI investigator (and the study’s lead author) Dr. JoAnn Manson, these findings lend support to the idea that estrogen, when it’s started near menopause, may slow the early stages of plaque buildup. “But estrogen’s effects are complex, and it has other known risks,” Dr. Manson points out, so it “shouldn’t be used for the express purpose of preventing cardiovascular disease.” Also, this study did not include older women, so there’s no indication of whether age makes a difference in the way estrogen affects plaque buildup. Only a randomized trial can test the “timing” hypothesis, and until then it remains unproven.

What about breast cancer?

Initial results from the WHI’s estrogen-only trial indicated that estrogen alone reduced the risk for breast cancer by 23% over about seven years. The effect was not statistically significant (meaning that it could have been due to chance), but it was still surprising in light of the increased risk found in the combined-hormone trial after four years. So investigators decided to take a closer look. In a final report — published in the April 12, 2006, issue of the Journal of the American Medical Association — they concluded that the women taking estrogen alone were at no greater risk for breast cancer than those taking a placebo.

The difference in risk between estrogen alone versus combined estrogen and progestin is one of the unanswered questions about hormone therapy and breast cancer. In the WHI, the estrogen-only takers had undergone hysterectomy, which is different from natural menopause. Also, we don’t know yet whether the time when hormone therapy starts influences breast cancer risk in the way it does heart disease risk. WHI investigators will soon report on a follow-up study of women in the estrogen-plus-progestin trial who continued to have annual mammograms after stopping their study medications in 2002. This could shed light on how long it takes for breast cancer risk to return to normal after women stop taking combined hormone therapy.

In the meantime, several groups of researchers reported in 2007 that the rate of new breast cancers began to decline in 2003, the year hormone therapy prescriptions fell off sharply.

Selected resources

Hot Flashes, Hormones, and Your Health, by JoAnn E. Manson, M.D., and Shari S. Bassuk, Sc.D., McGraw Hill, 2007.

Is it hot in here? Or is it me? by Pat Wingert and Barbara Kantrowitz, Workman Publishing, 2006.

What it means

Women in early menopause with troublesome hot flashes or night sweats can take short-term hormone therapy without increasing their risk for heart disease. Hormone therapy should be taken only for symptoms and, like any drug, for the shortest time possible and at the lowest effective dose (although we don’t know whether lower doses are actually safer). Studies suggest that estrogen patches may be less likely to cause blood clots in the legs than oral estrogen. For some women, the major menopausal complaint is vaginal dryness, which may persist for many years. Low-dose vaginal estrogen is an effective treatment for this symptom with negligible systemic effects.

When it comes to prevention, hormone therapy reduces the chances of fractures and colon cancer. Whether its adverse effect on the heart is related to timing still needs more study. But you can reduce these risks in other ways without increasing your odds for breast cancer, blood clots, and stroke. Avoid tobacco; exercise at least 30 minutes a day; adopt a healthy eating plan; and control your blood pressure, cholesterol, and blood sugar — with medications, if necessary. Be sure to get adequate calcium (1,200 milligrams per day) and vitamin D (800 to 1,000 IU per day). And if you’re at high risk for osteoporosis, there are many medications to choose from that curb bone loss.