Key T J, Pike M C
Imperial Cancer Research Fund's Epidemiology Unit, Radcliffe Infirmary, Oxford, U.K.
Eur J Cancer Clin Oncol. 1988 Jan;24(1):29-43. doi: 10.1016/0277-5379(88)90173-3.
The protective effect of early menopause shows that ovarian hormones increase the risk of breast cancer: it is likely that this is because they stimulate breast cell division. The mitotic rate of breast cells is higher during the luteal phase of the menstrual cycle than during the follicular phase, suggesting either that progesterone and oestrogen together induce more mitoses than oestrogen alone (the 'oestrogen plus progestagen hypothesis') or that oestrogen alone induces breast cell mitoses in a dose-dependent manner and that progesterone has no effect (the 'oestrogen alone hypothesis'). Both hypotheses are consistent with the known effects of reproductive history, obesity, combined oral contraceptives and oestrogen replacement therapy (ERT) on breast cancer risk, but while the oestrogen alone hypothesis predicts that hormone replacement therapy with oestrogen and a progestagen (HRT) will cause the same increase in risk as ERT, the oestrogen plus progestagen hypothesis predicts that HRT will cause a greater increase in risk than ERT. Both hypotheses suggest that the risk of breast cancer could be reduced by delaying the onset of regular ovulatory menstrual cycles and by minimizing the therapeutic use of oestrogens, and possibly of progestagens, in postmenopausal women. It may be possible to design hormonal contraceptives that will decrease breast cancer risk.
早期绝经的保护作用表明，卵巢激素会增加患乳腺癌的风险：这可能是因为它们刺激乳腺细胞分裂。月经周期黄体期乳腺细胞的有丝分裂率高于卵泡期，这表明要么是孕激素和雌激素共同诱导的有丝分裂比单独使用雌激素更多（“雌激素加孕激素假说”），要么是单独使用雌激素以剂量依赖的方式诱导乳腺细胞有丝分裂，而孕激素没有作用（“单独雌激素假说”）。这两种假说都与生殖史、肥胖、复方口服避孕药和雌激素替代疗法（ERT）对乳腺癌风险的已知影响一致，但虽然单独雌激素假说预测雌激素和孕激素联合激素替代疗法（HRT）将导致与ERT相同的风险增加，但雌激素加孕激素假说预测HRT将导致比ERT更大的风险增加。两种假说都表明，通过推迟规律排卵月经周期的开始以及尽量减少绝经后女性对雌激素（可能还有孕激素）的治疗性使用，可以降低患乳腺癌的风险。有可能设计出能降低乳腺癌风险的激素避孕药。
