Gooman & Gilman and other journal articles
The numbers are for Goodman &
Gilman’s The Pharmacological Basis of Therapeutics, 11th edition (2006), which I bought--a balanced source
for information.
Estrogen increases the risk of endometrial
cancer about 5 fold (thus the use of a prostaglandin). (1552).
Loss of tissue lining the vagina or bladder
leads to a variety of symptoms in many postmenopausal women. These include dryness
and itching of the vagina, dyspareunia, swelling of tissue in the genital region, pain during urination, a need to urinate
urgently or ofte3n, and sudden or unexpected urinary incontinence. (1553)
Gallbladder disease 2-3 fold.
Breast cancer through (a) stimulating
the growth rate of such cancer, (b) increase breast cell proliferation including those with mutations, (c) possible directly
through the production of a reactive chemical (4-hydroxycatechol) from the production of catechol estrogens. (1553).
Estrogens produce a favorable lipoprotein
profile, promote vasodilatation, inhibit the response to vascular injury, and reduce atherosclerosis. These effects should produce a reduction in cardiovascular disease in postmenopausal women; who ever in
a couple of clinical trials this was not substantiated. It is not clear if similar
results would occur with different drugs/dose in different patient populations. (1553)
The
Women’s Health Initiative also demonstrated that conjugated estrogen in combination with a progestin reduces the risk
of colon cancer by roughly one-half in postmenopausal women. (1554). As I commented
on my website, this more than makes up for the increased risk of breast cancer.
Osteoporosis: The primary mechanism by which estrogens act is to decrease bone
resorption; consequently, estrogens are more effective at preventing rather than restoring bone loss. Estrogens are most effective if treatment is initiated before significant bone loss occurs, and their maximal
beneficial effects require continuous use; bone loss continues if treatment is discontinued. (1553).
About 1980, epidemiological studies indicated
that this treatment increased the incidence of endometrial carcinoma. This led
to the use of HRT that includes a progestin to limit estrogen-related hyperplasia.
(1555).
Cardiovascular Disease: The incidence
of cardiovascular disease is low in premenopausal women, rising rapidly after menopause, and epidemiological studies consistently
showed an association between estrogen use and reduced cardiovascular disease in postmenopausal women (1553).
Postmenopausal Hormone Use and Primary Prevention of Heart Disease
and Stroke in Healthy Women
19 December 2000 | Volume 133 Issue 12 | Page S60
Summary on the web at http://www.annals.org/cgi/content/summary/133/12/933
The researchers studied 70,533 postmenopausal female nurses who
had no known history of previous cardiovascular disease.
Starting in 1978, the researchers began collecting information on
the type of hormones taken and, starting in 1980, on the dose of estrogen. Further follow-up surveys continued
to update information on hormone use and asked whether the women had had a heart attack or stroke. The
researchers confirmed all reported events, including deaths, by examining medical records and death certificates.
Women who took hormones were 40% less likely to have a heart attack
than those who never used hormones. The risk was reduced by about the same amount regardless of whether women had
taken high or low doses of estrogen. No difference in the risk for stroke was found between hormone
users and nonusers. However, women who took 0.625 mg or more of oral conjugated estrogen per day (an
average dose) and those who took estrogen with a progestin hormone had a higher risk for stroke than women who
never used hormones. Overall, women who had used postmenopausal hormones were about 23% less likely to have
a heart attack or stroke than women who had never taken them.
The Journal of Clinical Endocrinology
& Metabolism Vol. 87, No. 4 1509-1516.
Differential Effects of Oral Estrogen versus Oral Estrogen-Androgen
Replacement Therapy on Body Composition in Postmenopausal Women
Adrian S. Dobs, Tam Nguyen, Cindy Pace and Carla P. Roberts
Copyright © 2002 by The Endocrine Society.
Estrogen-androgen (E/A) therapy is also used
for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass. After E/A treatment, there were statistically significant increases in lean body mass
by 1.232 kg. When subjects were given self-reporting questionnaires,
more improvement was noted in sexual functioning and quality of life in the E/A group when compared
with patients receiving E alone. There were no noteworthy side effects. When subjects were given
self-reporting questionnaires, more improvement was noted in sexual functioning and quality of life in the
E/A group when compared with patients receiving E alone. There were no noteworthy side effects.
In conclusion, E/A replacement therapy can improve body composition, lower-body muscle strength, quality
of life, and sexual functioning in postmenopausal women.
J Reprod Med. 1998 Oct;43(10):847-56
Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual
behavior and neuroendocrine responses.
RESULTS: Estrogen-androgen
therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison
to previous estrogen therapy and postplacebo baseline assessments.
CONCLUSION: Sexual
desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined
estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy.
Journal of the National
Cancer Institute, Vol. 92, No. 4, 328-332, February
16, 2000
© 2000 Oxford University Press
Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin
{Estrogen alone 6% higher, estrogen + prosgestin 24% higher}
BACKGROUND: Hormone replacement therapy
(HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United
States in the 1960s and 1970s. Recent prescribing practices have favored combination
HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement
therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist
on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of
developing breast cancer in a population-based, case-control study. METHODS: Case subjects included
those with incident breast cancers diagnosed over 4 years
in Los Angeles County, CA, in the late 1980s and 1990s.
Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case
subjects and control subjects were interviewed in person to collect information on known breast cancer risk
factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal
control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer
risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously
for the different forms of HRT and for known risk factors of breast cancer. All P values are
two-sided.
RESULTS: HRT was associated with a
10% higher breast cancer risk for each 5 years of use (OR5 = 1.10; 95% confidence interval [CI] = 1.02-1.18).
Risk was substantially higher for CHRT use (OR5 = 1.24; 95% CI = 1.07-1.45) than for ERT
use (OR5 = 1.06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR5 = 1.38; 95%
CI = 1.13-1.68) than for CCRT (OR5 = 1.09; 95% CI = 0.88-1.35), but this difference was not
statistically significant. Conclusions: This study provides strong evidence that the addition of a progestin
to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have
important implications for the risk-benefit equation for HRT in women using CHRT.
