Whitehead M I
Acta Obstet Gynecol Scand Suppl. 1986;134:81-91. doi: 10.3109/00016348609157054.
Exogenous oestrogens are highly effective in relieving not only the acute symptoms of ovarian failure, such as vasomotor instability and vaginal dryness, but also in conserving postmenopausal bone mass. However, the oestrogen doses needed to achieve these benefits also induce endometrial proliferation. The risk of endometrial hyperplasia and carcinoma are thereby increased and unopposed oestrogen therapy is associated with a high incidence of abnormal vaginal bleeding requiring appropriate, invasive investigations. The cost-effectiveness of therapy and patient compliance are likely to be correspondingly reduced. Various strategies have been proposed to try to overcome the risk of endometrial hyperstimulation and these strategies have been reviewed. Based upon the available evidence, progestogen addition appears the most sensible and has been shown to be effective. It is now clear that progestogens should, in sequential therapies, be administered for 12 days each cycle for maximum protection. Concern has been expressed that the regular withdrawal bleed induced by sequential treatment will reduce patient compliance. Progestogens have, therefore, been added in a continuous fashion to try to prevent endometrial proliferation and thereby induce amenorrhoea. The ideal continuous, oestrogen/progestogen regimen has not yet been developed: all those evaluated to date are associated with a high incidence of breakthrough bleeding which is likely to restrict their use. Progestogens can cause undesirable physical, psychological and metabolic effects. The incidence and severity of side-effects will depend upon the type of progestogen prescribed, the route of administration, and the dose. Minimum effective daily doses of certain types of progestogens have now been established in terms of endometrial protection. Regrettably, few data are available on the physical and psychological effects of these progestogen doses: more information is available on lipid and lipoprotein effects but the data are confused and, at times, contradictory. More research is urgently needed to determine which of these progestogens is most suitable for addition to postmenopausal oestrogen therapy.
外源性雌激素不仅在缓解卵巢功能衰竭的急性症状（如血管舒缩不稳定和阴道干燥）方面非常有效，而且在维持绝经后骨量方面也很有效。然而，实现这些益处所需的雌激素剂量也会诱导子宫内膜增生。从而增加了子宫内膜增生和癌的风险，并且单纯雌激素治疗与需要进行适当侵入性检查的异常阴道出血的高发生率相关。治疗的成本效益和患者依从性可能会相应降低。已经提出了各种策略来试图克服子宫内膜过度刺激的风险，并且对这些策略进行了综述。根据现有证据，添加孕激素似乎是最合理的，并且已被证明是有效的。现在很清楚，在序贯疗法中，孕激素应每个周期给药12天以获得最大保护。有人担心序贯治疗引起的规律性撤药性出血会降低患者依从性。因此，已采用连续添加孕激素的方式来试图预防子宫内膜增生，从而诱导闭经。理想的连续雌激素/孕激素方案尚未制定出来：迄今为止评估的所有方案都与突破性出血的高发生率相关，这可能会限制它们的使用。孕激素会引起不良的身体、心理和代谢影响。副作用的发生率和严重程度将取决于所开孕激素的类型、给药途径和剂量。现在已经确定了某些类型孕激素在子宫内膜保护方面的最低有效日剂量。遗憾的是，关于这些孕激素剂量的身体和心理影响的数据很少：关于脂质和脂蛋白影响的信息较多，但数据混乱，有时相互矛盾。迫切需要更多研究来确定哪种孕激素最适合添加到绝经后雌激素治疗中。
