Pike M C, Peters R K, Cozen W, Probst-Hensch N M, Felix J C, Wan P C, Mack T M
Department of Preventive Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, CA 90033-0800, USA.
J Natl Cancer Inst. 1997 Aug 6;89(15):1110-6. doi: 10.1093/jnci/89.15.1110.
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.
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.
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.
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).
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.
20多年来人们已经知道，雌激素替代疗法会大幅增加女性患子宫内膜癌的风险。为降低这种增加的风险，孕激素已被以序贯方式（序贯雌激素 - 孕激素替代疗法）每月添加到雌激素替代疗法中5至15天（通常为7或10天），或与每剂雌激素替代疗法同时使用（连续联合替代疗法）。然而，目前对于在序贯雌激素 - 孕激素替代疗法中改变使用孕激素的天数的影响知之甚少。
我们试图确定序贯雌激素 - 孕激素替代疗法和连续联合替代疗法对女性患子宫内膜癌风险的影响。
进行了一项基于人群的病例对照研究，涉及833例病例受试者和791例对照受试者。女性首次被诊断为浸润性子宫内膜癌时已绝经、为白人且年龄在50 - 74岁，或在对照受试者匹配日期时年龄在50 - 74岁。所有受试者借助逐月日历接受面对面访谈。相对风险通过比值比（OR）估计；OR针对不同形式的激素替代疗法以及已知的子宫内膜癌风险因素进行了同时调整。
每使用5年雌激素替代疗法，调整后的OR为2.17（95%置信区间[CI] = 1.91 - 2.47）（基于病例受试者中的422名使用者和对照受试者中的262名使用者）。对于接受序贯雌激素 - 孕激素替代疗法且每月使用孕激素少于10天（实际为7天）的女性，每使用5年调整后的OR仅略微降至1.87（95% CI = 1.32 - 2.65）（74例病例受试者和47例对照受试者）。然而，当使用孕激素10天或更长时间（实际为10天）时，基本上没有增加的风险（每使用5年调整后的OR = 1.07；95% CI = 0.82 - 1.41）（79例病例受试者和88例对照受试者）。连续联合替代疗法也与基本上没有增加的风险相关（每使用5年调整后的OR = 1.07；95% CI = 0.80 - 1.43）（94例病例受试者和81例对照受试者）。
序贯雌激素 - 孕激素替代疗法中的孕激素需要给予至少10天才能有效阻断子宫内膜癌任何增加的风险。连续联合雌激素 - 孕激素疗法同样有效。两种方案均未降低女性患子宫内膜癌的潜在风险。在序贯雌激素 - 孕激素替代疗法中，使用孕激素少于10天（实际为7天）和10天或更长时间（实际为10天）的效果之间的明显差异表明，子宫内膜脱落的程度可能在确定子宫内膜癌风险中起关键作用。
