Intrauterine application of progestins in hormone replacement therapy: a review

The intrauterine application of progestins as endometrial protection against hyperstimulation by estrogen replacement therapy has been investigated in clinical trials since the early 1990s and one product has become available for this indication. This review considers the available published and presented reports on intrauterine use of progestin to date. Reports of 19 studies were reviewed. These studies included both peri- and postmenopausal women (826 in total), treated with different types of estrogens administered via various routes. Progesterone was used in two small studies, while all other studies used different doses of levonorgestrel for periods ranging from 6 months to more than 5 years. Endometrial effects, bleeding profiles, systemic effects (symptoms and metabolic), as well as clinical experience, were considered and were comparable to other forms of continuous combined hormone replacement therapy (HRT). It is concluded that the current evidence supports complete endometrial protection and a good safety profile. The observed bleeding profiles appear favorable but have not yet been directly compared with other forms of continuous combined HRT. A favorable effect on serum lipids has been observed and also awaits direct comparative confirmation. Progestin-attributable side-effects, effects on bone and breast tissues and other systemic effects have not yet been studied. Acceptance by patients has been good, while insertion did not present undue problems for the investigating physicians. Retention of the studied intrauterine systems has been very good. Intrauterine use of progestins, especially levonorgestrel, by purpose-designed systems as part of combined HRT, is a new way of administration and carries good benefits, while some aspects require more clinical evidence.