Safety and comfort of long-term continuous combined transdermal estrogen and intrauterine levonorgestrel administration for postmenopausal hormone substitution – a review

Abstract

Objective: To review the endometrial safety and patient acceptability of long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women.

Design: One-hundred and fifty-three women who utilized the regimen for 2 IUD cycles were followed-up for a period of 10 years. Histology of the endometrium was evaluated at the end of this period to assess endometrial safety and the acceptability of the method was assessed based on the replacement rate of the LNG-IUS and continuation of ET.

Results: The regimen, administered over a 10-year period, was very well tolerated and the IUD was retained well and no expulsions occurred. The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found.

Conclusion: The low systemic absorption of LNG could be desirable, thus allowing for maximization of the beneficial effects of ET on organ tissues (e.g. cardiovascular tissues and breast). Repeat LNG-IUS is associated with high patient satisfaction. If started before the age of 60, this regimen could be advised for lifelong prevention of cardiovascular disease and other prevention measures. The LNG-IUS was shown to effectively oppose the secondary effects of systemic estrogen on the endometrium tissue resulting in strong suppression during the entire period of EPT.

Chinese abstract

目的: 回顾长期连续应用经皮雌激素联合宫内释放的左炔诺孕酮（LNG）替代治疗对绝经后妇女子宫内膜的安全性和患者的接受性。

方法: 对153名按疗程使用2个IUD的女性进行长达10年的随访。随访结束时, 采用子宫内膜组织学检查评估子宫内膜的安全性, 同时以LNG-IUS的更换率和ET的持续来评估该方法的可接受性。

结果: 超过10年的管理显示, 该方案耐受性很好, 并且IUD保存完好, 无节育器脱落。绝大部分子宫内膜组织学图片显示为无活性的子宫内膜, 主要是以腺体萎缩和间质蜕膜化（Kurman分型5b）为特征。未发现子宫内膜增生的病例。

结论: LNG全身吸收率低是一个优势, 这使ET 对一些组织器官（例如心血管及乳腺）的有益的影响能最大化。LNG-IUS的再使用率与患者高满意度有关。如果60岁以前开始使用, 该方案能用于终生预防心血管疾病和其他预防措施。由于在整个EPT周期中都能强烈抑制, LNG-IUS能拮抗全身使用雌激素对子宫内膜的副作用。

• Acceptability
• endometrial histology
• endometrial suppression
• estro-progestogen therapy
• estrogen therapy
• intrauterine drug delivery system
• levonorgestrel
• tolerance

Acknowledgements

The author is grateful to Dr Kris Pylyser, Department of Histopathology, St. Augustinus Hospital, Veurne, Belgium for his contribution to the study by analyzing the biopsy specimen.

Declaration of interest

Dirk Wildemeersch, MD, PhD, has conducted research in the field of non-hormonal and hormonal, framed and frameless intrauterine devices for 30 years for contraception and treatment. He assisted in the development of the Femilis® LNG-IUS. He did not receive any financial compensation of any kind for this study. The author alone is responsible for the content and writing of this paper.