© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 1110-1116, Copyright © 1997 by Oxford University Press
MC Pike, RK Peters, W Cozen, NM Probst-Hensch, JC Felix, PC Wan and TM Mack
BACKGROUND: It has been known for more than 20 years that estrogen
replacement therapy substantially increases a woman's risk of developing
endometrial cancer. To reduce this increased risk, progestins have been
added to estrogen replacement therapy for between 5 and 15 days (usually 7
or 10 days) per "month" in a sequential fashion (sequential
estrogen-progestin replacement therapy) or with each dose of estrogen
replacement therapy (continuous combined replacement therapy). At the
present time, however, little is known about the effects of varying the
number of days that progestin is used in sequential estrogen-progestin
replacement therapy. PURPOSE: We sought to determine the effects of
sequential estrogen-progestin replacement therapy and continuous combined
replacement therapy on a woman's risk of developing endometrial cancer.
METHODS: A population- based, case-control study of 833 case subjects and
791 control subjects was conducted. Women were postmenopausal, white, and
aged 50-74 years when first diagnosed with invasive endometrial cancer or
were aged 50- 74 years at the matching date for control subjects. All
subjects were interviewed in person with the aid of a month-by-month
calendar. Relative risks were estimated by odds ratios (ORs); ORs were
adjusted simultaneously for the different forms of hormone replacement
therapy and for the known endometrial cancer risk factors. RESULTS: The
adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 years
of estrogen replacement therapy use (based on 422 users among the case
subjects and 262 users among the control subjects). For women who received
sequential estrogen-progestin replacement therapy with the progestin given
for less than 10 days (effectively 7 days) per month, the adjusted OR was
only slightly reduced to 1.87 (95% CI = 1.32-2.65) per 5 years of use (74
case subjects and 47 control subjects). However, when progestin was given
for 10 or more days (effectively 10 days), there was essentially no
increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.82-1.41)
(79 case subjects and 88 control subjects). Continuous combined replacement
therapy was also associated with essentially no increased risk (adjusted OR
= 1.07 per 5 years of use; 95% CI = 0.80-1.43) (94 case subjects and 81
control subjects). CONCLUSIONS: The progestin in sequential
estrogen-progestin replacement therapy needs to be given for at least 10
days to block effectively any increased risk of endometrial cancer.
Continuous combined estrogen- progestin therapy is similarly effective.
Neither regimen reduces a woman's underlying risk of endometrial cancer.
The sharp distinction between the effects of less than 10 days (effectively
7 days) and 10 or more days (effectively 10 days) of progestin use in
sequential estrogen- progestin replacement therapy suggests that the extent
of endometrial sloughing may play a critical role in determining
endometrial cancer risk.
ARTICLES
Estrogen-progestin replacement therapy and endometrial cancer
Department of Preventive Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, CA 90033-0800, USA.
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