Spicer D V, Ursin G, Parisky Y R, Pearce J G, Shoupe D, Pike A, Pike M C
University of Southern California School of Medicine, Los Angeles 90033-9987.
J Natl Cancer Inst. 1994 Mar 16;86(6):431-6. doi: 10.1093/jnci/86.6.431.
It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia.
Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group.
Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists.
Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance.
The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.
一段时间以来，人们已经知道口服避孕药能大幅降低子宫内膜癌和卵巢癌的风险，但不能降低乳腺癌风险。一种激素避孕方案已经研发出来，该方案使用促性腺激素释放激素拮抗剂（GnRHA）来抑制卵巢功能，并且此方案包括给予极低剂量的雌激素和孕激素。这种激素避孕方案试图将乳腺上皮对这些类固醇的暴露降至最低，并保留雌激素的最大有益作用，同时仍能预防子宫内膜增生。
我们的目的是确定与对照组女性相比，采用这种雌激素和孕激素水平降低的激素避孕方案的女性在基线至1年期间乳房X线密度是否发生变化。
21名女性按2:1的比例随机分为基于GnRHA的避孕组（14名女性）或对照组（7名女性）。避孕组接受以下治疗：每28天肌肉注射7.5mg醋酸亮丙瑞林缓释剂；每周7天中有6天口服0.625mg结合雌激素；每第四个28天周期口服10mg醋酸甲羟孕酮13天。对照组不接受任何药物治疗。两名放射科医生以盲法对避孕组和对照组受试者的基线和1年随访乳房X线照片进行了评估。
两组女性基线和1年乳房X线照片变化的比较显示，采用避孕方案的女性在1年时乳房X线密度显著降低（P = 0.039）。通过观察纤维间隔的细微程度来评估乳房X线密度的降低情况，结果显示避孕方案组存在高度显著差异（P = 0.0048）。一名采用避孕方案的女性因依从性差退出了研究。
与基线相比，激素避孕方案使乳腺对雌激素和孕激素的暴露减少，导致1年随访时乳房X线密度大幅降低。虽然没有直接证据表明这种密度降低会导致乳腺癌风险降低，但该方案具有保护作用的间接证据是，早期绝经可降低乳腺癌风险，且绝经与乳房X线密度降低有关。
