Hypothyroidism / Hormone Replacement Therapy - The Risks

submitted by Dr. Gary Farr Last Updated June, 4, 2002

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Hormone Replacement Therapy

HRT & BREAST CANCER

Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk.

Schairer C, et al.
JAMA 2000;283:485-491.

The results of this study, conducted on a sample population of 46,355 postmenopausal women, show that use of estrogen replacement therapy increases the risk of breast cancer by 20%. The addition of a progestin further increases the risk, and women who took an estrogen-progestin combination in the previous 4 years were found to have a 40% increased incidence of breast cancer, compared to nonusers. Each year of use of combination therapy increases the risk of breast cancer by 8%. The results of this study are important because they indicate that combination replacement therapy may be more dangerous than estrogens alone. Progestins have been added to estrogen replacement therapy because it was shown that unopposed estrogens increase the incidence of uterine cancer. Hormone replacement therapy (HRT), consisting of a combination of estrogen and progestin, is widely used to relieve symptoms of menopause and to prevent bone fractures and heart diseases, even though several studies have demonstrated no beneficial effects on heart diseases associated with HRT use, and some excess risk. Since, according to a survey performed by the North American Menopause Society, approximately one-third of U.S. women aged 45 to 65 years use some form of hormone replacement therapy, this increase in breast cancer risk can have enormous implications on the overall health of this population -some 16 million women. Women must be informed that there are no proven benefits associated with HRT while it is well established that treatment results in a significantly increased incidence of uterine cancer, breast cancer, stroke, gall bladder disease, deep venous thrombosis, pulmonary embolism, and possibly fatal and nonfatal myocardial infarction.

Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen

Versus Estrogen Plus Progestin.
Ross, RK et al.
J Natl Cancer Inst. 2000 Feb 16;92(4):328-332.

The results of this study, conducted on over 3,500 postmenopausal women, confirm that hormone replacement therapy (HRT) with estrogen and progestin increases the risk of breast cancer more than HRT with estrogen alone. The risk increases with duration of treatment, and for every 5 years of treatment the study demonstrated a 6% increased incidence of breast cancer in women using estrogen only, and a 24% increase in those using an estrogen-progestin combination, compared to nonusers.

Hormone replacement therapy and the risk of breast cancer

Nested case-control study in a cohort of Swedish women attending mammography screening.
Persson I, Thurfjell E, Bergstrom R, Holmberg L.
Int J Cancer 1997 Sep 4;72(5):758-61.

The results of this study show that women who use hormone replacement therapy for more than 10 years have a twofold increased risk of developing breast cancer, compared to nonusers. The risk is higher for women who use replacement therapy consisting of a combination of estrogen and progestin. In particular, use of unopposed estrogen for longer than 10 years after menopause is associated with a 30% increased breast cancer risk, while use of an estrogen-progestin combination is associated with a 2.4-fold increased risk.

The adverse effects of hormone replacement therapy.

Tavani A, La Vecchia C.
Drugs Aging 1999 May;14(5):347-57.

This article reviewed 51 epidemiological studies investigating the effects of hormone replacement therapy (HRT) on the risk of breast cancer. The results of the analysis showed that the risk of breast cancer increases by 2.3% for every year of HRT use. These data translate in an excess of 2, 6, and 12 breast cancers for every 1,000 women using HRT for 5, 10, and 15 years, respectively.

Hormone replacement treatment and breast cancer risk

A cooperative Italian study.
La Vecchia C, et al.
Br J Cancer 1995 Jul;72(1):244-8.

The results of this case-control study, conducted on 2569 women with breast cancer and 2588 controls, show that use of hormone replacement treatment (HRT) for 1 to 4 years is associated with a 20% increased risk of breast cancer, while use for 5 or more years is associated with a 50% increased risk of breast cancer. Women who had stopped HRT within the 10 previous years had a two-fold increased incidence of breast cancer, compared to nonusers.

HRT & OVARIAN CANCER

Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis.

Garg PP, Kerlikowske K, Subak L, Grady D.
Obstet Gynecol 1998 Sep;92(3):472-9.

In this study, the investigators analyzed the results of nine published study to determine whether there is an association between hormone replacement (HRT) therapy and invasive ovarian cancer. The results of the analysis revealed that the risk of ovarian cancer increases by 15% in women who had used at some point in their life HRT, and by 27% in those who used it for more than 10 years, compared to nonusers.

Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis of European studies.

Negri E, et al.
Int J Cancer 1999 Mar 15;80(6):848-51.

This study analyzed 4 previous case-control studies conducted on 1,470 women with ovarian cancer and 3,271 controls, to determine the impact of hormone replacement therapy (HRT) on ovarian cancer. The results of the analysis revealed that users of HRT have a 70% increased risk of ovarian cancer, compared to nonusers.

Estrogen replacement therapy and risk of epithelial ovarian cancer.

Risch HA.
Gynecol Oncol 1996 Nov;63(2):254-7.

The results of this study show that women who use estrogen replacement therapy for 5 or more years have a 2-fold increased risk of developing ovarian cancer of the serous type and a 2.8-fold increased risk of developing ovarian cancer of the endometroid type, compared to nonusers.

Hormone replacement therapy and risk of epithelial ovarian cancer.

Purdie DM, et al.
Br J Cancer 1999 Oct;81(3):559-63.

The results of this study show that estrogen replacement therapy increases the risk of ovarian cancer of the endometrioid or clear cell type by 2.5 times. Women with an intact genital tract are particularly susceptible, their risk being 3 times higher than that of women with a history of hysterectomy or tubal ligation.

HRT & UTERINE CANCER

Risk of endometrial cancer following estrogen replacement with and without progestins.

Weiderpass E, et al.
J Natl Cancer Inst 1999 Jul 7;91(13):1131-7.

The results of this study show that women using unopposed estrogen replacement therapy have an over 6-fold increased risk of uterine cancer, compared to nonusers. Women who use combination hormone replacement therapy (HRT) with a progestin added to the estrogen for fewer than 16 days of the cycle have a 3-fold increased risk of uterine cancer. Use of HRT with a progestin added continuously during the cycle is associated with an 80% reduction of risk of uterine cancer.

Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement.

Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C.
Cancer Causes Control 1999 Aug;10(4):253-60.

The results of this study, conducted on a sample population of 11,231 Swedish women employing hormone replacement therapy, show that use of estrogens alone for 6 years and longer is associated with an over 4-fold increase in uterine cancer, compared to nonuse. The risk of uterine cancer is significantly attenuated by use of estrogens combined with a progestin, with a 40% non-significant excess risk in users of combination therapy for longer than 6 years. In addition, the study found that use of estrogens combined with progestins for 1 to 6 years and 6 or more years is associated with a 40% and 70% increased risk of breast cancer, respectively, compared to nonuse.

Menopausal hormone use and endometrial cancer, by tumor grade and invasion.

Shapiro JA, Weiss NS, Beresford SA, Voigt LF.
Epidemiology 1998 Jan;9(1):99-101.

The results of this study show that use of unopposed hormone replacement therapy (HRT) for 3 or more years is associated with a 5-fold increased risk of uterine endometrial cancer, while use of combination HRT with a progestin added cyclically or continuously is associated with a 30% increased risk of endometrial cancer.

Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy.

Hunt K, Vessey M, McPherson K, Coleman M.
Br J Obstet Gynaecol 1987 Jul;94(7):620-35.

The results of this study, conducted on 4544 postmenopausal women who employed hormone replacement therapy (HRT) for a median of 5.5 years, show that users of HRT have an almost 3-fold increased incidence of uterine cancer and a 60% increased incidence of breast cancer, compared to nonusers. In 43% of women, HRT was of the "opposed" type, although the amount of progestin they received was generally inferior to that employed in more recent times.

HRT: MISCELLANEOUS

Postmenopausal estrogen replacement therapy and the risk of developing systemic lupus erythematosus or discoid lupus.

Meier CR; Sturkenboom MC; Cohen AS; Jick H.
J Rheumatol, 25(8):1515-9 1998 Aug.

The results of this study show that women who use either estrogen-only or combined hormone replacement therapy for 2 years or longer, have a 5-fold and 2-fold increased risk of developing systemic lupus erythematosus and discoid lupus, respectively, compared to nonusers.

Hormone replacement therapy in systemic lupus erythematosus.

Kreidstein S, Urowitz MB, Gladman DD, Gough J.
J Rheumatol 1997 Nov;24(11):2149-52.

The results of this study show that while hormone replacement therapy (HRT) does not increase the number of lupus flares in patients with lupus, it significantly increases the duration of the disease. In particular lupus lasted an average of 18 years in patients taking HRT, and an average of 5.6 years in patients not on hormones.

Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus.

Sanchez-Guerrero J, Liang MH, Karlson EW, Hunter DJ, Colditz GA.
Ann Intern Med 1995 Mar 15;122(6):430-3.

The results of this study, conducted on almost 70,000 women aged 30 to 55 years who were followed up for an average of 15 years, show that women who used postmenopausal hormone replacement therapy (HRT) had a twofold increased incidence of lupus, compared to nonusers. Current and past use of HRT was associated with a 2.5-fold and 80% increased risk of lupus, respectively. The risk of lupus increased with increasing duration of HRT use.

Urinary tract infections and estrogen use in older women.

Orlander JD; Jick SS; Dean AD; Jick H.
J Am Geriatr Soc, 40(8):817-20 1992 Aug.

The results of this study show that older women taking exogenous estrogens have a two-fold increased risk of urinary tract infections, compared to nonusers. The risk of urinary tract infections is not increased in women who had their uterus removed.

Postmenopausal hormone use and cholecystectomy in a large prospective study.

Grodstein F, Colditz GA, Stampfer MJ.
Obstet Gynecol 1994 Jan;83(1):5-11.

The results of this study, conducted on 54,845 postmenopausal women, show that users of hormone replacement therapy have a two-fold increased risk of undergoing gall bladder removal, compared to nonusers. The risk of gall bladder removal increases with the duration of hormone use, and is 2.6-folds higher in current users of postmenopausal hormones for longer than 10 years, compared to nonusers.

Increased risk of cholecystectomy in users of supplemental estrogen.

Petitti DB, Sidney S, Perlman JA.
Gastroenterology 1988 Jan;94(1):91-5.

The results of this study show that users of estrogen replacement therapy have a two-fold increased risk of gall bladder removal, compared to nonusers. The risk is increased by 2.7-folds in current users of postmenopausal estrogens, and by 60% in past users.