Home | KEEPING YOUR BELOVED CENTERED ON YOU--jk | LIFE-LONG LOVERS: how to--JK | WHY WOMEN LIVE LONGER | HRT concise summary--jk | HORMONE REPLACEMENT THERAPY REVIEWED--WOMEN--JK | HRT is safe--Scientific American | Genes, estrogen receptors, and breast cancer | ONE TYPE OF ESTROGEN LOWERS THROMBOSIS RISK | POST MENOPAUSE SEX STATS | Tamoxifen side effects--avoid | PM WOMEN ON ESTROGEN LOOK YOUNGER | ESTROGEN SUPPLEMENT REDUCES HEART DISEASE | ORAL CONTRACEPTIVES NOT ASSOICATED WITH BREAST CANCER | HRT-- MORE STUDIES SUPPORT IT | HRT, SEVERAL STUDIES, ABSTRACTS | Mechanism of how estrogen accelerates cancer | Acupuncture versus Estrogen for Hot Flashes | BRAIN AS CLOCK FOR MENOPAUSE--Scientific American article | ESTROGEN PREVENTS ARTHRITIS | Osteoporosis Screen: What you need to know | Femur Fractures Bisphosphonate Treatment | Runners 40% greater bone density | Ovarian Cysts, an overview | TESTOSTERONE FOR WOMEN? | 55% Breast Implants leak--FDA study finds | Genetic risk for breast cancer | CERVICAL CANCER RISK FACTOR | Polycystic Ovarian Syndrome | Pap Smear, Once every 5 years recommended | Breast Cancer Tests Frequently Wrong | FDA's ARTICLE ON MENOPAUSE | ASPIRIN REDUCES C-SECTION 400%--meta-study reveals--another shows reduces breast cancer | downers during pregnancy harm baby | Women Health Links


Enter subhead content here

Oral contraceptive use is not associated with increased breast cancer risk

Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002;346:2025-2032.

Neither current nor former use of combined estrogen plus progestin oral contraceptives (OCs) is associated with increased risk for breast cancer in women, according to the results of this population-based, case-control study. Investigators interviewed 4,575 women with breast cancer and 4,682 women without breast cancer. Women were aged 35 to 64; 77% of the case subjects and 79% of the controls had used some type of OC. Compared with never users, the relative risk of breast cancer was 1.0 (95% CI, 0.8-1.3) for current OC users and 0.9 (95% CI,0.8-1.0) for former users. The relative risk did not increase consistently with longer periods of OC use, higher doses of estrogen, type of progestin used, or age at first use. Also, women with a family history of breast cancer did not have an increased risk from OC use.

Level II-2 evidence

Comment. Oral contraceptives are the most widely used reversible method of contraception used by US women (approximately 78% of participants in this large study were ever users). They provide consistent users with convenient, effective, and reversible birth control. Furthermore, use of OCs is associated with important noncontraceptive health benefits, ranging from lighter less painful more regular menses to prevention of endometrial and ovarian cancers. Perhaps the biggest concern that women, and their clinicians, have regarding OCs is that their use might increase breast cancer risk. This large, NIH-sponsored, CDC-conducted, study provides a high level of reassurance that OC users, regardless of age, formulation type, duration of use, or family history, will not increase their breast cancer risk.

Andrew M. Kaunitz, MD
Professor and Assistant Chairman
Department of Obstetrics and Gynecology
University of Florida Health Science Center
Director of Menopause and Bone Density Services
Medicus Diagnostic Center
Jacksonville, FL


By Joseph M. Kowalski, M.D.
Director of Investigational Interventions
Cardiovascular Institute of the South

A new epidemiological study suggests that the heart benefits of estrogen supplements for post menopausal women continue quite late in life.

The study by the University of Pittsburgh Medical School found a 30 percent reduction in heart disease in white women age 65 to 74 who take estrogen supplements. The findings reinforce previous government research that revealed a 25 percent reduction in heart disease among women age 45 to 64 who took estrogen supplements.

Women rarely experience heart attacks before menopause. Researchers believe that estrogen offers some protection against the blood vessel blockage that causes heart attacks and strokes. Studies suggest that estrogen increases the "good" high-density lipoprotein (HDL) and lowers the "bad" low-density lipoprotein (LDL) in the blood, thus slowing the rate at which plaque builds up in the arteries.

Another recent report that strongly suggested a connection between estrogen levels and lower rates of heart attack came out of ongoing research at Harvard Medical School. The analysis of 32,000 nurses for four years in the Nurses Cohort Study showed that those taking estrogen appeared to have one half the risk of heart attack of those not taking the hormone.

The Harvard study also showed that women who go through early menopause (before age 40) have a significantly higher risk of heart disease. The study and its findings link the ovaries and its hormones --- estrogen and progesterone --- to heart health.

According to an article in the New England Journal of Medicine co-authored by investigators at Harvard Medical School and its affiliated Brigham and Women's Hospital, "...post menopausal women who take estrogen generally have lower rates of cardiovascular disease than women of similar age who do not take estrogen."

In the 1970s, when estrogen was first prescribed as a birth control measure for women, researchers feared elevated doses of estrogen would put women at higher risk for stroke and high blood pressure. Studies in the past 35 years have not confirmed those fears. Instead, they persist in showing that estrogen supplements for post-menopausal women provide a prolongation of the natural protection from heart disease they enjoyed in their child-bearing years.

Nevertheless, women enjoying the heart disease-resisting benefits of estrogen are in a minority. Only 15 to 30 percent of post-menopausal women in this country now take estrogen supplements -- in part because of concerns that it may be linked to an increase in the incidence of some cancers.  

Low doses of vaginal estradiol cream treat urogenital atrophy with no adverse endometrial effects

Santen RJ, Pinkerton JV, Conaway M, et al. Treatment of urogenital atrophy with low-dose estradiol: preliminary results. Menopause 2002;9:179-187.

A vaginal cream estradiol dose as low as 10 µg is effective for treating urogenital atrophy and does not cause endometrial hyperplasia or increased estradiol levels, according to the preliminary findings from this single-blind, single-arm study. The study is designed to determine the effects of low doses of vaginal estrogen on symptoms of urogenital atrophy, vaginal pH, and vaginal and urethral cytology. Women receive vaginal estradiol daily for 3 weeks then twice weekly for another 9 weeks. Of the first 7 women who received the 10-µg dose, all were responders — vaginal and urethral cytology improved, vaginal pH decreased, and endometrium remained atrophic. Later stages of this study will look at doses as small as 1.25 µg.

Level II-1 evidence

Comment. This study indicates that ultra-low doses of vaginal estradiol do not stimulate the endometrium, at least over the short term. Estradiol vaginal cream improved the vaginal and urethral cytology and decreased vaginal pH, but the endometrium remained atrophic. Caution should be expressed, but these results will probably be true over the long term, especially since vaginal estradiol is better absorbed than through more normal mucosa.

R. Don Gambrell, Jr. MD
Clinical Professor of Endocrinology and Obstetrics and Gynecology
Medical College of Ge


Oral estrogen replacement therapy slows progression of atherosclerosis

Hodis HN, Mack WJ, Lobo RA, et al, for the Estrogen in Prevention of Atherosclerosis Trial (EPAT) Research Group. Estrogen in the prevention of atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001(Dec 4);135:939-953.

Healthy postmenopausal women who take oral estrogen replacement therapy (ERT) with 17-beta estradiol have a slower rate of progression of subclinical atherosclerosis than women taking placebo, according to results from this randomized, double-blind, placebo-controlled trial. A total of 222 postmenopausal women without pre-existing cardiovascular disease received either ERT (1 mg/day unopposed oral 17-beta estradiol) or placebo. Participants had low-density lipoprotein (LDL) cholesterol levels of 130 mg/dl (3.37 mmol/L) or higher. All women received dietary counseling. A lipid-lowering agent was prescribed if LDL levels exceeded 160 mg/day (4.15 mmol/L); 57% of the estradiol group and 66% of the placebo group received these medications. During the 2-year trial, the average rate of progression of subclinical atherosclerosis (as measured by B-mode ultrasound of the common carotid artery) was significantly lower in ERT recipients than in placebo recipients (P = 0.046). Average rates of progression did not differ between women who were assigned estradiol and placebo recipients who were assigned lipid-lowering medications. Estrogen therapy had no additional effect on the progression of atherosclerosis in women receiving lipid-lowering therapy.

Comment. The positive results of this randomized clinical trial in healthy women taking unopposed oral 17-beta estradiol with the endpoint of carotid intima-media thickness stand in direct opposition to other recent HRT trials in women with cardiovascular disease or CHD risk factors. Differences in women’s cardiovascular health at baseline, age, years since menopause, type of estrogen, and presence or absence of progestogen may all contribute to the differences in trial results. Importantly, this trial (EPAT) also found no added benefit of combined estrogen and lipid-lowering therapy on the progression of subclinical atherosclerosis. The positive findings of EPAT provides another important piece of the evolving puzzle of the relationship between estrogen and cardiovascular disease in women, and they underscore the importance of continuing the WHI and WISDOM trials to assess the effect of estrogen on clinical outcomes such as heart attack and stroke in healthy women.

Cynthia A. Stuenkel, MD
Clinical Professor of Medicine
Endocrinology and Metabolism
University of California, San Diego
San Diego, CA


Longer-term HRT use significantly reduces the risk of recurrent coronary events

Grodstein F, Manson JE, Stampfer MJ. Postmenopausal hormone use and secondary prevention of coronary events in the Nurses’ Health Study. Ann Intern Med 2001(July);135:1-8.

The risk for recurrent major coronary events seems to increase among users of short-term hormone replacement therapy (HRT, either with or without a progestogen) who have established coronary heart disease (CHD) but appears to decrease with longer-term use, according to data from the Nurses’ Health Study. This prospective, observational cohort study sought to determine a time trend in the risk for recurrent heart disease among postmenopausal women with CHD. A total of 2,489 postmenopausal women with previous myocardial infarction (MI) or documented atherosclerosis were evaluated. Investigators observed a significant trend toward decreasing risk for recurrent major CHD events with longer duration of HRT use. Short-term and current users of HRT had an adjusted relative risk of 1.25 (95% CI, 0.78-2.00) compared with never users. For longer-term users (at least 2 years), the risk was significantly lower than in never users (RR, 0.38; 95% CI, 0.22-0.66). Overall, with up to 20 years of follow-up, the relative risk for a recurrent CHD event among current HRT users was 0.65 (95% CI, 0.45-0.95).

Comment. This latest report from the Nurses’ Health Study responds to an issue raised by the HERS trial — whether short-term use of HRT can, in some women, increase the risk of recurrent CHD events. In this data set, there was a nonsignificant trend toward increased risk in short-term users of HRT. However, in women who used HRT for two or more years, the risk was significantly reduced. This trend echoes the retrospective analysis of the Puget Sound Group Health Cooperative, which showed a short-term increased risk and a longer-term reduced risk of recurrent CHD events. In the aggregate, these data continue to raise concerns about an early increase in risk of CHD events in women with established disease. But in longer-term users, benefit may accrue over time.

David M. Herrington, MD
Associate Professor of Medicine/Cardiology
Wake Forest University School of Medicine
Winston-Salem, NC



Both ERT and HRT improve skin-aging measures

Sator P-G, Schmidt JB, Sator MO, Huber JC, Hönigsmann H. The influence of hormone replacement therapy on skin ageing: a pilot study. Maturitas 2001;39:43-55.

Estrogen replacement therapy, either with or without a progestogen, had a significant beneficial effect on skin aging in postmenopausal women, according to this study from Austria. A total of 24 women (mean age, 54.9 years) who had not received estrogen or hormone replacement therapy for at least 6 months were randomly assigned to one of four groups: transdermal estrogen alone, transdermal estrogen plus a progestogen (vaginal suppository), oral estrogen plus a progestogen (vaginal suppository), or an unblinded control group receiving no therapy. Skin measurements were taken monthly for skin surface lipids, epidermal skin moisture, skin elasticity, and skin thickness. After the 6-month treatment regimen, mean levels of epidermal skin moisture, skin elasticity, and skin thickness were significantly improved in all treatment groups compared with the control group. The surface lipid measure was significantly improved for both combined estrogen plus progestogen therapy groups compared with the controls.

Comment. This article presents a comprehensive survey of clinical, subjective, and physical measures of the effect of ERT and HRT on skin aging. Although limited in statistical power by both design and the small number of participants, this study demonstrates a convincing clinical benefit to the skin from the three different regimens. The portion of the effect due to enhanced collagen probably parallels the effect of estrogen on bone density, as type I collagen is the predominant collagen in both skin and bone. From a clinical standpoint, women’s subjective reaction to aging skin can be a powerful stimulus to initiate or continue ERT/HRT. The benefits of a fuller dermis and less dryness can be directly touted as clear advantages of treatment.

Laurence J. Meyer, PhD, MD
Associate Professor, Dermatology and Internal Medicine
University of Utah Health Sciences Center
Salt Lake City, UT

HRT moderates blood pressure gains in postmenopausal women

Scuteri A, Bos AJG, Brant LJ, et al. Hormone replacement therapy and longitudinal changes in blood pressure in postmenopausal women. Ann Intern Med 2001(Aug 21);135:229-238.

Postmenopausal women taking hormone replacement therapy (estrogen plus a progestin; HRT) have less of an increase in systolic blood pressure (BP) over time than women not taking HRT, according to the Baltimore Longitudinal Study of Aging, an observational study that began recruiting participants in 1978. Cardiovascular risk factors are among the measurements taken at baseline and every 2 years thereafter. For this report, data were analyzed for 226 normotensive, postmenopausal women (mean age 64) with an average follow-up of 5.7 years (range 2 to 18 years); 77 were HRT users and 149 used neither drug. After adjustment for confounding factors, the average systolic BP increase was statistically smaller in HRT users than in nonusers: 1.6 mm Hg (range 1.3-1.9 mm Hg) versus 8.9 mm Hg (range 8.6-9.2 mm Hg), respectively. Diastolic BP was not statistically different between the two groups.

Comment. Interpretation of this study is challenging due to the rolling enrollment into this prospective cohort study and the complex statistical modeling that is required to analyze such data. Nevertheless, the results are consistent with the growing body of evidence indicating that HRT acts as a vasodilator that may attenuate age-related increases in systolic BP. Whether this effect will translate into a cardiovascular benefit with respect to clinical cardiovascular events has not yet been established.

David M. Herrington, MD
Associate Professor of Medicine/Cardiology
Wake Forest University School of Medicine
Winston-Salem, NC

Comment. Studies have demonstrated that BP in midlife women increases with age, especially after age 55. With hypertension being a major risk factor for development of CHD, identification of any factors that might affect the level of BP merits aggressive consideration. This study, although observational, suggests that women using HRT may experience a lower incidence of elevation in systolic BP than nonusers. Of significant importance is the finding that HRT use may have a positive effect on BP over time by limiting the usual systolic elevations that occur with age, even considering the extraneous factors of body mass index, lipids, smoking status, and physical activity.

Diane Todd Pace, PhD, APRN, BC
Family Nurse Practitioner/Researcher
Regional Medical Center of Memphis
Memphis, TN



The problem with many of the later studies is that they used a prostaglandin which blocked the therapeutic effect of estrogen upon neuron.

 Estrogen replacement therapy and risk of Alzheimer disease

Archives of Internal Medicine, Vol. 156 No. 19, October 28, 1996

A. Paganini-Hill and V. W. Henderson
Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, USA.

BACKGROUND: With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. OBJECTIVE: To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. STUDY DESIGN AND METHODS: A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (+/- 1 year). RESULTS: The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (i.e., injections and/or creams) routes of administration. The risk decreased significantly with both increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). CONCLUSION: This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.

Enter supporting content here