I always say go as low as you can with estrogen dosing, and this is an article proving the wisdom and efficacy of "quarter-dose" estrogen therapy. That is, quarter of the standard dosing. Cool part is this is a study of "bioidentical" estradiol -- the same estrogen your body makes and not yet another synthetic version (although the levo-norgestrel is synthetic - don't take that stuff!). The commentary is by the North American Menopause Society (www.menopause.org), a conventional but solid organization. We always want to be guided by Level 1 evidence -- meaning randomized controlled trials, as this is the way we can make sure we are safe with how we dose hormones. This is an important new study to integrate into your thinking about whether to use estrogen after menopause. Healthy holidays, SG

Microdose of transdermal 17β-estradiol effectively relieves hot flashes 

Bachmann GA, Schaefers M, Uddin A, Utian WH. Lowest effective transdermal 17β-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2007;110:771-779. Level of evidence: I. 

A microdose of 17β-estradiol relieves hot flashes 
in a significant proportion of postmenopausal 
women, found this randomized, double-blind, 
placebo-controlled, multicenter trial that 
compared a low-dose 2.2 mg 17β-estradiol/0.69 
mg levonorgestrel combination transdermal patch 
with a microdose 1.0 mg 17β-estradiol 
transdermal patch with a placebo patch in healthy 
postmenopausal women in 48 centers in the 
United States. A total of 425 postmenopausal 
women aged 40 years and older (mean age, 52.7 
y) were enrolled who had at least 7 moderate or 
severe hot flashes per day or at least 50 per week. 
The study measured the mean changes from 
baseline in frequency and severity of hot flashes 
with hormone therapy (HT) compared with 
placebo at weeks 4 and 12 of treatment, as well as 
the proportion of responders with at least 75% and 
90% reduction in frequency of moderate and 
severe hot flashes. 


Of the total, 145 women received the 17β- 
estradiol/levonorgestrel patch, which delivered 
0.023 mg/day and 0.0075 mg/day of the drugs, 
respectively. There were 147 women who 
received the estradiol-only patch, which 
delivered 0.014 mg/day of the drug. Placebo 
was given to 133 women. The mean weekly 
frequency of hot flashes at baseline was similar 
for the three groups, as were the mean daily 
severity scores. 

At week 12, the mean frequency of hot flashes 
was significantly reduced in the low-dose group 
(–51.80; P < 0.001) and microdose group 
(–38.46; P < 0.001) compared with placebo. 
Reductions in severity scores for hot flashes 
were equally significant in the low-dose and 
microdose groups compared with the placebo 
group. Reductions in frequency of hot flashes 
were larger with the low-dose combination, but 
41% of women in the microdose 17β-estradiol 
group had a 75% or greater reduction in 
frequency of hot flashes from baseline at week 
12, and 35% had a 90% reduction in frequency. 
In this group, the mean reduction in moderate 
and severe hot flashes was 70% after 4 weeks of 
treatment and 90% after 8 weeks. The time 
frame for the onset of efficacy was similar in the 
low-dose 17β-estradiol group. To treat with the 
lowest effective dose, the findings support the 
notion of starting treatment for hot flashes at the 
microdose and then adjusting the dosage upward 
if symptom relief is not achieved after 8 weeks. 

Comment. In their paper, Bachmann et al report a 
significant lowering of hot flashes (at least 7/d or 
50/wk) with a microdose of transdermal estradiol 
(a patch delivering 0.014 mg/d) with maximum 
efficacy at 8 weeks. This is the lowest dose yet 
that shows efficacy for hot flashes and suggests 
that there is no threshold minimal dose as was 
once previously believed. This dose is also known 
to protect bone. 

The time required to achieve maximum effect is 8 
weeks, however, and for some women this may be 
unacceptably long. But some patients respond 
more quickly so an acceptable reduction may be 
seen earlier. 

Recent findings about standard-dose HT have 
been reassuring, but use of the lowest effective 
dose of any medication is an important goal of 
clinical practice, presumably because lower doses 
are associated with fewer side effects and are 
more likely safer.1 Current guidelines around the 
world unanimously recommend the use of the 
lowest effective dose of HT. 

Lower HT doses, when used with adequate doses 
of progestogen, have an excellent endometrial 
safety profile and in some studies less breast pain. 
Surprisingly, in this study breast pain did not 
differ between the groups. Microdoses were 
associated with less bleeding but the lower dose 
was combined with a progestin and only lasted 12 
weeks, making comparisons difficult. Some have 
suggested that ultralow or microdose estrogen 
may not require regular progestogen or that lower 
progestogen doses might be safe because little to 
no endometrial stimulation is expected at these 
doses. The lack of uterine-related consequences of 
unopposed ultralow-dose estrogen was 
demonstrated in a study of nonhysterectomized 
postmenopausal women, aged 60 to 80 years, 
receiving unopposed transdermal estradiol (14 
μg/d). Compared with placebo, women receiving 

estrogen had similar rates of endometrial 
hyperplasia, endometrial proliferation, and 
vaginal bleeding over the course of 2 years of 
treatment.2 

The effect of lower estrogen and/or progestogen 
doses on breast cancer risk in HT users is 
unclear and there is little evidence at this time to 
address this important clinical issue. Recent 
evidence suggests that ultralow-dose HT has a 
neutral effect on mammographic breast density, 
which may be a predictor of breast cancer and 
make mammographic reading more difficult.3 

Overall, low- and ultralow-dose formulations 
are increasingly becoming the first choice for 
the initial management of menopause-related 
symptoms, particularly as women pass from 
their most symptomatic phase or, as the authors 
point out, wish to restart therapy. Ultralow-dose 
regimens may be especially attractive for 
relieving menopause-related symptoms as well 
as for prevention of bone loss. These factors and 
the improved tolerability profile compared with 
standard-dose regimens impart a favorable 
benefit-risk profile and suggest an important 
role for the lowest dose HT regimens in and 
postmenopausal management. 

Michelle P. Warren, MD 
Professor of Medicine and Ob/Gyn 
Medical Director, Center for Menopause, Hormone 
Disorders, and Women’s Health 
Wyeth-Ayerst Professor of Women’s Health 
Columbia University 
New York, NY 
Member, NAMS Professional Education Committee 
Member, NAMS Board of Trustees 

References: 
1. Ettinger B. Personal perspective on low-dosage 
estrogen therapy for postmenopausal women. Menopause 
1999;6:273-276. 
2. Johnson SR, Ettinger B, Macer JL, Ensrud KE, Quan J, 
Grady D. Uterine and vaginal effects of unopposed 
ultralow-dose transdermal estradiol. Obstet Gynecol 
2005;105:779-787. 
3. Boyd NF, Rommens JM, Vogt K, et al. Mammo- 
graphic breast density as an intermediate phenotype for 
breast cancer. Lancet Oncol 2005;6:798-808.

This is an article that was published earlier this year showing that hormones improves skin.  We all knew that already but it's always good to have high-quality proof.  These hormones are not all good - synthetic hormone therapy can cause breast cancer, stroke, blood clots and heart disease, but we need to understand the benefits so we can make informed, empowered decisions instead from a place of fear.  SG

Sator PG, Sator MO, Schmidt JB, et al. A prospective,

randomized, double-blind, placebo-controlled study on 

the influence of a hormone replacement therapy on skin

aging in postmenopausal women. Climacteric 2007;

10:320-334. Level of evidence: I.

 

Menopausal hormone therapy (HT) has a positive

effect on skin in postmenopausal women,

according to a prospective, randomized, double-

blind, placebo-controlled study that examined the

effect of treatment with Femoston for 7 months.

The trial included 40 women between ages 44

and 55 (mean age, 51.3 y). The mean duration of

amenorrhea was 46.6 months in the HT group

and 39 months in the placebo group. The women

received the HT, a combination of 2 mg 17β-

estradiol/10 dydrogesterone, for seven 28-day

cycles. 

 

Women in the study visited the blinded

investigators at screening, randomization, weeks

7 and 13 of treatment, and weeks 1 to 3 after

treatment. Skin properties were measured by

noninvasive measures. Skin elasticity, skin

surface lipids, skin hydration, and skin thickness

were measured at time of randomization, week

13 of treatment, and at 1 to 3 weeks after

treatment. Instruments used to measure skin

properties included the Sebumeter, the

Corneometer, and high-frequency  ultrasound.  In 

addition, a clinical dermatological exam of skin

status was performed. After 7 months of HT,

there were significant improvements in skin

elasticity, skin hydration, and skin thickness. The

dermatological exam was in concordance with

these results.

 

Comment. The condition of the skin is one of the

most visible signs of aging and has been

especially important to women’s sense of

attractiveness. Ingestion or topical application of

hormones is not a new strategy for inhibiting

aging. Estrogen and progesterone were common

cosmetic additives until laws prohibited the

inclusion of ingredients that altered the structure

and function of the skin.1 The presence of

hormone receptors in the skin and the dermal

benefits of HT are well documented, primarily in

European studies.2-6 No doubt the results of this

study will be of interest to the growing sector of

the population that spends millions of dollars on

Botox therapy, cosmetic surgery, and antiaging

skin moisturizers—results of the successful

marketing of “looking younger” in the twenty-

first century. 

 

This study by Sator et al reports the findings of a

small European study of the influence of an oral

HT preparation, Femoston (not marketed in the

United States), on aging skin. All 40 participants

were reported to have medically indicated

 2

reasons for taking HT. Three women in each

group withdrew or were lost to follow-up, with a

resulting sample size of 34 women. The paper

includes numerous tables with detailed results of

multiple statistical comparisons between baseline

measures and comparable assessments at 3

months and 7 months post initiation of therapy. 

 

Although there are numerous statistically

significant findings, the clinical significance,

given the small sample size, is not apparent. With

so many comparisons reported, there is a greater

chance of there being spurious statistically

significant findings. One important finding,

however, was that the skin benefits were more

pronounced in women who initiated HT close to

the date of their final menses. The authors note

that the success of the therapy is likely to be

directly related to the timing of initiation and

duration of treatment. Possible harmful side

effects of HT were not noted. The short duration

of the intervention (7 mo) is also a limitation. A

variety of questions about prescribing HT for

cosmetic or quality of life reasons were raised.

 

Both the US Food and Drug Administration

(FDA) and NAMS have clearly indicated that

until reliable evidence proves otherwise, we must

assume that the risks and benefits of all systemic

estrogens are the same. Clearly, women who are

prescribed HT for medically indicated reasons

may experience positive skin effects. But

prescribing systemic HT for the express reason of

skin benefits is not warranted. Local estrogen

therapies provide clear benefits to vaginal and

vulvar tissue. And, for women with extremely

dry, inelastic, and poorly hydrated skin, HT

would be the treatment of choice for improving

their quality of life. However, larger, double-

blinded, well-controlled studies of topical

therapies are needed before HT as an antiaging

skin therapy can be considered.

 

Catherine L. Juve, PhD, MPH, WHNP, RN

Professor, School of Nursing

University of Minnesota

Minneapolis, MN

Member, NAMS Professional Education Committee

References:

1. Draelos ZD. Topical and oral estrogens revisited for

antiaging purposes. Fertil Steril 2005;84:291-292.

2. Patriarca MT, Goldman KZ, Dos Santos JM, et al.

Effects of topical estradiol on the facial skin collagen of

postmenopausal women under oral hormone therapy: a

pilot study. Eur J Obstet Gynecol Reprod Biol 2007;

130:202-205.

3. Hall G, Phillips TJ. Estrogen and skin: the effects of

estrogen, menopause, and hormone replacement therapy 

on the skin. J Am Acad Dermatol 2005;53:555-568.

4. Holzer G, Riegler E, Hönigsmann H, Farokhnia S,

Schmidt JB. Effects and side-effects of 2% progesterone

cream on the skin of peri- and postmenopausal women:

results from a double-blind, vehicle-controlled, randomized

study. Br J Dermatol 2005;153:626-634.

5. Brincat MP, Baron YM, Galea R. Estrogens and the

skin. Climacteric 2005;8:110-123.

6. Naftolin F. Prevention during the menopause is critical

for good health: skin studies support protracted hormone

therapy. Fertil Steril 2005;84:293-294.

 

We know that one quarter of women at or past menopause note vaginal thinning, irritation, decreased sexual response or dryness, and seek medical attention for it. I find the numbers are actually much higher if you ask women routinely. I'm a big fan of natural lubricants first, and if that doesn't work, try a tiny dose of natural estriol vaginal cream. I like estriol because you usually need less of it than the other forms of estradiol. It is by prescription, and needs to be formulated by a reliable compounding pharmacy. The good news is that it takes about 2 weeks to re-estrogenize the tissues, and it also prevents bladder infections. Remember that pre-menopausal women can have thiss too -- especially thin women who don't have much estrogen on board. Below are some guidelines, published by the North American Menopause Society. SG New Guidelines Issued for Treatment of Vaginal Atrophy News Author: Laurie Barclay, MD CME Author: Charles Vega, MD May 15, 2007 — The North American Menopause Society (NAMS) has issued a 2007 position statement about the treatment of vaginal atrophy with local vaginal estrogen. The guidelines, which are published in the May-June issue of Menopause, state that therapy should be guided by clinician and patient preference. Using the general principles established for evidence-based guidelines, NAMS convened a panel of clinicians and researchers with expertise in genitourinary disease to review, synthesize, and interpret the current evidence on vaginal estrogen therapy for vaginal atrophy, develop conclusions, and make recommendations. The advice of this expert panel was used to assist the NAMS Board of Trustees in publishing this position statement. "Although hot flashes typically accompany the loss of ovarian estrogen production at menopause, they usually abate over time regardless of whether estrogen therapy is used," Editorial Board Chair Gloria A. Bachmann, MD, said in a news release. "In contrast, vaginal symptoms (eg, vaginal dryness, vulvovaginal irritation and itching, and painful intercourse) are usually progressive and unlikely to resolve spontaneously. Left untreated, vaginal atrophy can result in years of discomfort, with a significant impact on quality of life." About 10% to 40% of postmenopausal women have symptoms related to vaginal atrophy, most of whom require treatment. However, only about 25% of symptomatic women seek medical attention. The therapeutic standard for moderate to severe vaginal atrophy is estrogen therapy, administered either vaginally at a low dose or systemically. There has been a relative lack of randomized controlled trials performed to date, but they have shown that low-dose, local vaginal estrogen delivery is effective and well tolerated for treating vaginal atrophy. In North America, US Food and Drug Administration–approved treatments of vaginal atrophy symptoms that offer localized vaginal delivery of estrogen include cream, tablet, and ring formulations. These products are associated with fewer adverse effects than systemic estrogen. At the doses recommended in labeling, all of the low-dose vaginal estrogen products approved in the United States for treatment of vaginal atrophy are equally effective. The choice of treatment should therefore be individualized based on clinical experience and patient preference. In general, creams may be associated with more adverse effects than ring or tablet formulations, perhaps because there is more potential for women to apply higher-than-recommended dosing with cream. However, a Cochrane review reported no significant differences among the delivery methods in terms of hyperplasia, endometrial thickness, or the proportion of women with adverse events. The most commonly reported adverse effects associated with vaginal estrogen therapy are vaginal bleeding and breast pain, with nausea and perineal pain reported less frequently. When low-dose estrogen is administered locally for vaginal atrophy, progestogen is generally not indicated. Data are insufficient to recommend annual endometrial surveillance in asymptomatic women using vaginal estrogen therapy. Vaginal estrogen therapy should be continued as long as women continue to have distressing symptoms. Management of vaginal atrophy is similar for the group of women without a cancer history and for women treated for non–hormone-dependent cancer. However, for women with a history of hormone-dependent cancer, management recommendations are individualized and vary based on each woman's preference in consultation with her oncologist. Specific recommendations are as follows: The primary goals of vaginal atrophy management are symptom relief and reversal of atrophic anatomic changes. For women with vaginal atrophy, first-line treatments include nonhormonal vaginal lubricants and moisturizers. Symptomatic vaginal atrophy that does not respond to nonhormonal vaginal lubricants and moisturizers may require prescription therapy. Randomized controlled trials in postmenopausal women are limited. However, they have demonstrated that low-dose, local, prescription vaginal estrogen delivery is effective and well tolerated for treating vaginal atrophy while limiting systemic absorption. Low-dose vaginal estrogen products approved in the United States for treating vaginal atrophy include estradiol vaginal cream, conjugated estrogens vaginal cream, the estradiol vaginal ring, and the estradiol hemihydrate vaginal tablet. These are equally effective at the doses recommended in labeling, so specific choice depends on clinical experience and patient preference. When low-dose estrogen is administered locally for vaginal atrophy, progestogen is generally not indicated. Closer surveillance may be required for women at high risk for endometrial cancer, those using a higher dose of vaginal estrogen therapy, or those with symptoms such as spotting or breakthrough bleeding. Evidence is insufficient to recommend annual endometrial surveillance in asymptomatic women using vaginal estrogen therapy. Vaginal estrogen therapy should be continued for as long as women have distressing symptoms. For women treated for non–hormone-dependent cancer, management of vaginal atrophy is similar to that for women without a cancer history, but for those with a history of hormone-dependent cancer, management recommendations should be based on each woman's preference and the advice of her oncologist. "Overall, subjective improvement occurs in 80% to 90% of women treated with local vaginal estrogen," the authors conclude. "Vaginal atrophy unresponsive to estrogen may be due to undiagnosed dermatitis/dermatosis or vulvodynia, so treatment failure warrants future evaluation and careful examination." Novo Nordisk supported the development of this position statement through an unrestricted educational grant. Members of the Editorial Board have disclosed various financial relationships with Berlex, Duramed, Johnson & Johnson, Pfizer, Roche, Wyeth, Paladin Labs Canada, Wyeth Canada, Procter & Gamble, and/or Merck. Menopause. 2007;14:357-369.

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.

I'm on vacation but cannot resist posting this info. I advise my patients to go nonhormonal with contraception - condoms, rhythm method, IUD, or Fem Cap. Here's more data to add to the mounting pile of adverse effects associated with hormonal contraception! SG Hormonal Contraception and Cervical Cancer Risk Risk for cervical cancer increased in current users of hormonal contraception but declined after use stopped. Cervical cancer risk is increased in current and recent users of hormonal contraception, but the effect’s duration has not been delineated. To quantitate this risk more precisely, investigators pooled data on 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 studies. Analyses were stratified by potential confounders (e.g., study site, time since last use, and type of contraceptive [oral or injectable; combined oral estrogen-progestogen or progestogen only]). The risk for cervical cancer was higher in current users of combined oral contraceptives than in never users (relative risk, 1.9 with more than 5 years’ use). After cessation of use, the risk declined, equaling that of never users in 10 years. The increase in risk did not vary substantially with human papillomavirus status, although confidence intervals were wide because of limited numbers. Data were insufficient for fully comparable analyses of progestogen-only and injectable contraceptives. Comment: Although this careful analysis confirms an increase in risk for cervical cancer among women using hormonal contraception, the finding should not dissuade clinicians from providing such contraception. The increased risk could reflect biologic interaction or confounding by sexual behavior: Women who use hormonal contraception are less likely to use barrier methods and so are more likely to be exposed to HPV, some types of which are documented cervical carcinogens. However, among women with oncogenic HPV infection, use of hormonal contraception has not been shown to affect the natural history of HPV-induced dysplasia (Journal Watch Women’s Health Feb 7 2006). Furthermore, hormonal contraception decreases parity, thereby reducing other causes of morbidity and mortality — especially in the developing world. Women choosing hormonal contraception can also be reassured that cytologic screening as well as HPV vaccination and testing are effective methods for preventing cervical cancer. — Anna Wald, MD, MPH Published in Journal Watch Women's Health December 20, 2007