GYN.COM PRESENTS

LIFE LONG WOMEN'S HEALTH CARE

ERIK N. COHEN, M.D. AND ASSOCIATES

MENOPAUSE AND HORMONE REPLACEMENT

Controversy regarding the decision to either begin or remain on post menopausal hormone replacement has become a decision in which the well informed patient  has lost faith in whom to believe.  Is it the physician who can be trusted to be fully informed?  Is it the popular press who has fully research the literature?  Is it the physician who is famous for writing a book who knows the truth? Sadly, there is no truth no matter what you read or are told.  Rather, there are many scientific  studies many of which contradict each other.  There is no one study as yet that answers the dilemma.  The answer is still to be determined as an individual decision.

To begin the explanation of menopausal management, we must define menopause as the failure of the body to produce hormones which were at one time produced by the female ovary.  The average age of natural ovarian failure remains approximately age 52.The remaining years of life expectancy to approximately age 87 will be in an estrogen deficient body.  While in the early 1900"s life expectancy being nearly 50 years the issue of estrogen lack seemed not to be important. In the 21st century a female can expect to live nearly one half of her life without the estrogen that her body was accustomed to.

The effects of estrogen are many.  There are both beneficial and potential risks. Now complicating the decision is the awareness that a different hormone that is at times given with estrogen may also have effects which may alter the estrogen actions.

There are two main medical hormonal management methods. The choice is based upon whether the woman has a uterus or not. HRT stands for "Hormonal Replacement Therapy", which implies the combination of estrogen plus a progestin. ERT implies "Estrogen Replacement Therapy".  

Many scientific studies have shown that estrogen given alone TO A WOMAN WITH A UTERUS may lead to UTERINE cancer.  These studies have confirmed that NO increased risk of cancer of the uterus is found when  a progestin drug is given along with the estrogen. Therefore a majority of physicians will administer a progestin along with estrogen when a uterus is present.  The specific type, dose, timing, and frequency of progestin is under continued investigation.

Recently, the press has focused on two studies regarding the issue of post menopausal hormone therapy.  The Women's Health Initiative (WHI), and the Heart and Estrogen Replacement Study (HERS) both have been used to criticize hormone therapy. Unfortunately, other studies which contradict the WHI and HERS interpretation have not been as widely reported. To help one to better make their own decision, this controversy will be explored.

Women's Health Initiative (WHI)

The WHI is a large scale study of estrogen and combination estrogen plus a progestin.  It was designed to evaluate risk to benefit ratio in the postmenopausal woman of estrogen replacement therapy (ERT) and estrogen/progestin replacement therapy (HRT).  27,000 women were enrolled between 1993 and 1998, and the study is scheduled to conclude in 2005.

The Data and Safety Monitoring board informed the public on July 9, 2002 that on their May 31, 2002 meeting  they recommended to 1. Discontinue the trial group using .625 mg of conjugated estrogens combined with 2.5 mg of medroxyprogesterone acetate 2. But to continue the trial group using daily unopposed estrogen.

The monitoring board took this step because of a developing trend in year number 5 of the study which did not reach clinical significance.  The board did not consider other studies such as Dupont et. al. Cancer. 1999;85:1277-1283 which showed that estrogen did not increase the risk of breast cancer in women with biopsy prove proliferative (hyperplasia) of the breast. The study of breast cancer and type (histology) that according to Li et. al. Cancer. 2000;88:2570-2577 that showed that if cancer developed in a person using HRT it would tend toward the lobular type that are associated with a higher survival. Nor did they refer to the study that shows that breast cancer survivors can use HRT without increasing the risk of recurrence. (DiSala et. al. Am J Clin Oncol. 2000;23:541-545

The National Health and Nutrition Examination Study (NHANES) found no increased risk of breast cancer with HRT.(Lando et al. Am J Prev Med. 1999;17:176-180) Those authors stated that their 22 year study of 5761 post menopausal women. including 73,253 person years of follow up was "evidence that if there is an increase of breast cancer associated with HRT use, this risk is small."

The USC breast cancer study results did show a risk with the addition of a progestin but when it was sequential per five years of use. (Ross et al. J Natl Cancer Inst. 2000;92:328-332) They noted that current practice is using lower amount of progestin.  The authors noted that  the diferences could be due to chance alone and that the benefit from reduction in other risks while taking HRT outweighed and possible increased risk.

The Iowa Women's Health Study followed patients for 11  years and did not have a significant increase in risk, and though the trend increased, the confidence limit of interpretation of the data widened.  The Collaborative Group on Hormonal Factors in Breast Cancer analysis of several studies suggested that cyclic progestin may have an independent effect on breast cancer.  Their data do not suggest an independent effect of continuous combined HRT.

Data in fact suggests that breast cancer if it occurs in HRT users may be different in that tumor is smaller, more well differentiated, and less spread. This results in a better survival in a woman who develop breast cancer while on HRT, when compared to woman not on HRT.

The WHI study is criticized in that it failed to take in account (because of its short length) that breast cancer take 10 years to develop.  The WHI studies are consistent with hormonal stimulation of pre-existing tumors. Because the study was discontinued, the follow up survival data is not available.

Most important to note on the WHI study was that the hazard risk by year six was decreasing again back to where there was not an increase in risk.  This was thus approaching what the other longer studies had found.

In regard to the WHI interpretation of evaluating the primary prevention effects of estrogen on heart disease, experts feel that this study could answer that question as the average age of the participants is 63.  21% of the participants were in their 70's, while 45% were in their 60's.  Because of the age of the study participants, it is assumed that a significant number  had pre existing atherosclerosis (heart disease).  Again if we look at the prior studies we already were aware that the beneficial effects of estrogen  are diminished with increasing heart disease.  

Other studies regarding heart disease have shown that the use of a lipid lowering drug (i.e. a statin) plus the use of a baby aspirin significantly lowers the risk of heart disease. The WHI has not indicated the use of these drugs during the continuing years of the study. According to Dr. Leon Speroff, "there is evidence that the beneficial effect of estrogen on the cardiovascular system is lost on women already taking statins" (Hodis et al. Ann Intern Med 2001;135:939-953) .

The WHI study also confirmed in a randomized study a reduction in osteoporotic fractures including hip and vertebral. There is no randomized data to show that the alternatives to estrogens are effective in preventing fractures.

More good news is that this randomized study did show a 37% reduction in colon cancer for HRT users. Uterine cancer, lung cancer, and other cancers were NOT affected.

Perhaps while the press talks about 26% increases in invasive breast cancer, 29% increases in heart disease, 41% increases in strokes, a better view would be to show how small these changes really are. In breast cancer we are talking about 8 additional cases per ten thousand person years and not taking in account the improved survival rates shown in women taking HRT. We expect that the 38 women who developed breast cancer will live longer than the 30 women who were not on HRT, based upon the studies previously mentioned. Regarding heart disease, the increase was most seen in non fatal heart attacks.  Blood clot rates were only 18 more  per ten thousand person years. We would expect that in this older age group a baby aspirin and the use of a lipid lowering drug may have significantly reduced these numbers.

Copyright © 2001 Erik N. Cohen M.D. and Associates
Last modified: July 22, 2002