Primary choice of estrogen and progestogen as components for HRT: a clinical pharmacological view

Abstract

Prescribing hormone replacement therapy (HRT) requires consideration of the selection of its two components, the estrogen and the progestogen. In terms of the estrogen, the decision is mainly whether to use estradiol (E2) or conjugated equine estrogens (CEE). These are the components needed to efficiently treat climacteric symptoms or/and prevent osteoporosis, currently the only labeled indications. There is still controversy regarding the adequate dosages comparing E2 and CEE; however, the consensus is that the differences in the efficacy of E2 and CEE are not a real issue. Therefore, other criteria have to be used. The first reason to add the progestogen is to avoid the development of endometrial cancer (i.e. to achieve ‘endometrial safety’). Any available ‘fixed-combined’ HRT preparation has to be tested for sufficient endometrial efficacy, because the first question the health authorities ask before product registration relates to endometrial safety. We can generally rely on the endometrial safety of these fixed-combined products. However, it could be that we want to use ‘free’ combinations, which are necessary if we use transdermal E2 (patches, gel, spray), but also to individualize schedules, for example when treating bleeding problems. The question here is how to attain knowledge about the endometrial efficacy of the different progestogens and how to monitor therapy. We will try to answer these two questions from a ‘clinical pharmacology’ point of view, as a discipline which preferably considers pharmacological properties, but also relating to clinical practice, to achieve individualized therapy with optimal efficacy, best tolerability and minimal risks.

摘要

激素替代疗法(HRT)需要考虑其两种组分的选择, 雌激素和孕激素。在雌激素选择方面, 主要考虑决定用雌二醇(E2)还是用结合雌激素(CEE), 这是有效治疗更年期症状或/和预防骨质疏松症所需的组分, 治疗更年期症状或/和预防骨质疏松症是目前HRT唯一的适应证。对E2和CEE的足够剂量仍有争议；然而, 共识认为E2和CEE的有效性效差异并不是一个真正的问题。因此, 不得不使用其他标准评价。添加孕激素的首要原因是为了避免子宫内膜癌的发生（即“子宫内膜安全”）。任何已有的“固定组合”HRT制剂都必须经过足够的子宫内膜有效性保护的测试, 因为卫生当局在产品注册前询问的第一个问题是关于子宫内膜安全性。我们一般可以信赖这些固定组合产品的子宫内膜安全性。然而, 我们可能想用“自由”组合, 如我们用经皮E2（贴剂、凝胶、喷雾剂）, 添加孕激素是必要的, 例如在治疗出血问题时要个性化治疗。问题是如何获得关于不同孕激素的子宫内膜有效保护的知识, 以及如何监测安全效果。我们将试图从“临床药理学”的视角回答这两个问题, 作为一门最好考虑药理特性的学科, 但与临床实践有关, 以实现最佳疗效、最佳耐受性和最小风险的个体化治疗。

Keywords:

• Estrogen
• progestogen
• hormone replacement therapy
• pharmacological choice

Potential conflict of interest

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Beijing Municipal Administration of Hospitals’ Ascent Plan [No. DFL20181401]; National Natural Science Foundation of China [No. 81671411].