Adashi E Y
Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore 21201.
Hum Reprod. 1994 Jul;9(7):1380-97. doi: 10.1093/oxfordjournals.humrep.a138715.
The introduction of steroid 'add-back' regimens draws on the recognition that several clinical entities targeted for treatment with gonadotrophin-releasing hormone agonist (GnRHa) are not '6-month diseases'. Included under this heading are individuals suffering from symptomatic endometriosis (not desires of pregnancy), uterine fibroids (ineligible or disinterested in definitive surgical therapy), ovarian hyperandrogenism, premenstrual syndrome, menopausal transition, or dysfunctional uterine bleeding. A 6-month course of therapy with a GnRHa does not adversely affect lipoprotein economy and therefore presumably the corresponding cardiovascular risk. A 6-month course of GnRHa therapy appears to be associated with a substantial decrease (of up to 8.2%) in lumbar bone density, a phenomenon which may not be entirely reversible 6 months after discontinuation of therapy. In principle, steroid 'add-back' therapy should diminish some or all of the side-effects associated with GnRHa therapy, may provide a medical treatment option for patients representing a high surgical risk, and may delay surgical intervention if desired. On the other hand, a steroid 'add-back' therapy may delay tissue diagnosis, be associated with a substantial cost as well as with the need for parenteral route of administration. Norethindrone-only (but not medroxyprogesterone acetate-only) 'add-back' regimens have proved promising in the context of endometriosis. Non-concurrent oestrogen/progestin 'add-back' regimens proved promising in the context of uterine fibroids. Substantial additional studies would have to be carried out to validate the utility of steroid 'add-back' regimens. Special emphasis will have to be placed on the evaluation of long-term utility with an eye towards assessing clinical efficacy, impact on lipoprotein economy, impact on bone density, impact on urogenital tissues, and impact on the hot flush. The concurrent or non-concurrent use of non-steroid 'add-back' regimens will also most likely constitute a major component of future studies.
甾体“反加”疗法的引入基于这样一种认识，即几种使用促性腺激素释放激素激动剂（GnRHa）治疗的临床病症并非“6个月就能治愈的疾病”。这一类别包括患有症状性子宫内膜异位症（非妊娠意愿）、子宫肌瘤（不符合或对确定性手术治疗不感兴趣）、卵巢雄激素过多症、经前综合征、围绝经期、或功能失调性子宫出血的个体。GnRHa治疗6个月疗程不会对脂蛋白代谢产生不利影响，因此推测也不会影响相应的心血管风险。GnRHa治疗6个月疗程似乎与腰椎骨密度大幅下降（高达8.2%）有关，这种现象在停药6个月后可能不会完全逆转。原则上，甾体“反加”疗法应能减轻与GnRHa疗法相关的部分或全部副作用，可为手术风险高的患者提供一种医学治疗选择，并可根据需要延迟手术干预。另一方面，甾体“反加”疗法可能会延迟组织诊断，成本高昂，且需要胃肠外给药途径。仅使用炔诺酮（而非仅使用醋酸甲羟孕酮）的“反加”疗法在子宫内膜异位症方面已被证明很有前景。非同时使用雌激素/孕激素的“反加”疗法在子宫肌瘤方面已被证明很有前景。还必须进行大量额外研究以验证甾体“反加”疗法的效用。必须特别强调对长期效用的评估，着眼于评估临床疗效、对脂蛋白代谢的影响、对骨密度的影响、对泌尿生殖组织的影响以及对潮热的影响。非甾体“反加”疗法的同时或非同时使用也很可能构成未来研究的一个主要组成部分。
