Whitehead M I, Fraser D
Obstet Gynecol Clin North Am. 1987 Mar;14(1):299-320.
The major hazard of postmenopausal cyclic estrogen therapy is endometrial hyperstimulation. The incidence of hyperplasia is dose dependent; the incidence of carcinoma is both dose and duration dependent. The risk of carcinoma is small. Invasive procedures such as endometrial biopsy to detect those patients with hyperplasia and carcinoma are unlikely to be cost-effective and have other disadvantages. With cyclic estrogens, biopsies should be performed at regular intervals irrespective of the bleeding pattern. The possible alterations to cyclic treatments to reduce the risk of endometrial hyperstimulation have been reviewed; only progestogen addition has been shown to be effective. Maximal effects are obtained when progestogens are added for 12 to 13 days each calendar month. To reduce the risk of side effects, the minimum dose of progestogen should be prescribed, and with the nor-testosterone derivatives, a small dose of norethindrone, approximately 1 mg daily, is as effective as 5 mg daily. The smaller doses cause minimal lipid changes. Interpatient variation in response to the 17-hydroxyprogesterone derivatives can occur, and at high doses, adverse lipid effects have been reported. With sequential estrogen/progestogen therapies, the endometrial histology appears to correlate with the bleeding pattern, thereby, perhaps, obviating the need for biopsy. The development of regimens to induce endometrial atrophy and amenorrhea is suboptimal, and further research is required.
绝经后周期性雌激素治疗的主要风险是子宫内膜过度刺激。增生的发生率与剂量有关；癌症的发生率与剂量和持续时间均有关。患癌风险较小。诸如子宫内膜活检等侵入性检查手段来检测那些患有增生和癌症的患者不太可能具有成本效益，且还有其他缺点。对于周期性雌激素治疗，无论出血模式如何，都应定期进行活检。已对为降低子宫内膜过度刺激风险而对周期性治疗可能进行的调整进行了综述；仅添加孕激素已被证明是有效的。当每个日历月添加孕激素12至13天时可获得最大效果。为降低副作用风险，应开具最低剂量的孕激素，对于去甲睾酮衍生物，小剂量的炔诺酮（约每日1毫克）与每日5毫克的效果相同。较小剂量引起的脂质变化最小。患者对17 - 羟孕酮衍生物的反应可能存在个体差异，且高剂量时已报道有不良脂质效应。对于序贯雌激素/孕激素疗法，子宫内膜组织学似乎与出血模式相关，因此或许无需进行活检。诱导子宫内膜萎缩和闭经的方案尚不完善，需要进一步研究。
