Goals

1. Understand the data and trends of the WHI.
2. Understand the available data and how the WHI relates
   to this.
3. Understand why women need Postmenopausal hormone and estrogen
   therapy.

Article

Risks and Benefits of Estrogen plus Progestin in Healthy
Postmenopausal Women JAMA, July 17, 2002 – Vol 288:
321-333 Copyrighted 2002, American Medical Association

1. Studied 16,608 women average age 63 randomized to oral
   horse estrogen(OHE) 0.625mg and medroxyprogesterone acetate(MPA)
   over average time of 5.2 years.
2. All women received the same dose or placebo with no exclusions
   for women at risk for thrombotic disease.
3. Statistical analysis reported to press and discussed in
   article used nominal confidence intervals(CIs), not adjusted
   CIs as recommended by their statisticians.
4. Only significant adjusted CIs were an increased risk of
   deep vein thrombosis and a decreased risk of “other”
   osteoporotic fractures.
5. Trends in all conditions similar to old observational
   studies.
6. Stopped for alleged increased of breast cancer, but average
   time from first cell to mammographically diagnosable breast
   cancer is almost 7 years; there is no new breast cancer,
   only earlier diagnosis.
7. Cardiovascular disease was increased in the first 2 years
   from giving oral horse estrogen to women at risk, then the
   rise in risk is parallel until after 5 years there is a
   geometric increase in the rate of CV disease in the control
   group. These results are parallel to observational studies
   reported in 1996.
8. Breast cancer is rising at parallel rates as the study
   ends. Note that at no time do women in the control group
   not develop the same number of cancers within 1 year or
   less!
9. Colon cancer is rising geometrically in the control group
   as the study ends and slowly in the OHE/MPA group.
10. Hip fractures are rising in a marked geometric fashion
    as the study ends in the control group and decelerating
    in the OHE/MPA group.

Other Studies

Current perspectives on benefits and risks of hormone replacement
therapy. Burkman RT et al Am J Obstet Gynecol 2001;185:S13-S23

1. Cardiovascular disease significantly decreased.
2. Alzheimer’s disease significantly decreased.
3. Fractures significantly decreased.
4. Breast cancer risk with little or no increase.

Breast cancer and hormone replacement: collaborative reanalysis
of data from 51 epidemiological studies of 52,705 women with
breast cancer and 108,411 women without breast cancer. Collaborative
Group on Hormonal factors in Breast Cancer. Lancet 1997; 350:
1047-59

1. Interpreted incorrectly as showing a significant increase
   in risk of diagnosis of breast cancer after 10 years use.
2. Increase is statistically significant but not important.
   Not important because women who never took HRT have just
   as much breast cancer 11 to 15 months after the women on
   HRT for 10 years.
3. Again showing HRT leads to earlier diagnosis of breast
   cancer explaining the better prognosis of women on HRT when
   diagnosed.

Effect of oestrogen during menopause on risk and age at onset
of Alzheimer’s disease Tang MX, et.al. Lancet 1996: 431

1. Prospective study on risk of Alzheimer’s disease in menopause
   by testing each year.
2. Risk of Alzheimer’s dramatically decreased:

Hormone Replacement Therapy and Incidence of Alzheimer’s
Disease in Older Women The Cache County Study Zandi PP, et
al JAMA 2003; 288:1111 Copyrighted 2002, American Medical
Association

1. Men and women in Cache County, Utah were tested yearly
   for Alzheimer’s disease.
2. Women on hormones for the greater then 10 years had a
   dramatic decrease in risk of Alzheimer’s to the same as
   men.

Postmenopausal Hormone Therapy and Mortality, Grodstein et
al NEJM, June 19, 1997 – Vol 336: 1769-1775.

1. Mortality significantly decreased if on HRT from:
   

   a.	All causes	37%
   b.	Coronary heart disease	53%
   c.	All cancer	29%

2. Mortality is decreased significantly if on HRT/ERT and
   woman has risk factors:

   a.	High Cardiovascular Risk	49% decrease in overall mortality
   b.	Breast cancer in mother or sister	35%
   c.	Age 50 to 59	37%
   d.	Age 60 to 73	42%
   e.	Age at menopause <49	42%
   f.	Age at menopause >54	38%
   g.	Current Smoker	45%
   h.	Surgical Menopause	29%
   i.	Natural Menopause	41%
   j.	Thin,Normal, or Obese	37 to 46%

Hormone replacement therapy and the risk of death from breast
cancer: A systematic review. Nanda K et al, Am J Obstet Gynecol
186:325-334.

Risk of death from breast cancer either decreased or unchanged.

Summary and Recommendations

1. WHI has limited useful data.
2. Breast cancer risk is NOT increased.
3. CV disease, Alzheimer’s, Colon cancer, and mortality are
   all decreased in most studies.
4. Hormones have widespread benefit with minimal risk.
5. Risk of Alzheimer’s is most dramatically decreased.
6. Do not use oral horse estrogen and medroxyprogesterone
   acetate in new start patients.
7. Use the lowest effective dose of estradiol or estrone
   to give a physiologic level of estradiol or total estrogen.
   Low dose ethinyl estradiol may also be used.
8. Use the lowest dose of a progestin or progesterone to
   protect from endometrial cancer.
9. Do not use oral hormones in women at risk for thrombotic
   disease.
10. Use transdermal hormones to decrease total dose and avoid
    liver metabolism on “first pass”.
11. Vaginal atrophy reflects the atrophy occurring throughout
    the body.
12. Osteoporosis is just one soft tissue that can be measured
    but reflects the “porosis” of all the soft tissues.
13. Do not substitute hormones for other preventive supplements
    and therapies such as low dose aspirin, diet, exercise,
    statins and other lipid lowering treatments, ACE inhibitors,
    calcium supplements, bisphonates, etc.
14. Continue estrogen and hormones life long, do not stop
    after 5 years,10 years,15 years or any time.
15. Discontinue estrogen and hormones at the same age and
    for the same reasons that it is recommended that men be
    castrated for their good health. (NEVER!)