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There is a large body of knowledge about the local morphological and functional effects on the endometrium with progestogen exposure. This review has particularly focused on the effects of intrauterine LNG administration. It is disappointing that to date no single factor has emerged that directly correlates with the aberrant endometrial bleeding associated with any of the methods of progestogenonly contraception. It is therefore probable that several factors acting closely together will contribute to the pathogenesis of these abnormal bleeding patterns experienced by women. The eventual elucidation of such factors will facilitate the development of intervention strategies designed to overcome the BTB experienced with progestogen-only contraception. Thereafter progestogen-only contraceptive methods will gain increased user satisfaction and women may benefit from other health gains, especially if the progestogen is delivered locally to the uterine cavity.

The development of uterine receptivity depends on the action of progesterone through the PR. Blocking or modulating the effect of progesterone through PR antagonists, modulators or agonists provide new insight into the role of progesterone as well as on the nature of endometrial receptivity and provides the ground for the development of new treatment options for infertility and contraception. A number of biochemical or morphological markers, whose expression coincides with the downregulation of progesterone receptors and the development of receptivity, have been studied. The expression of some of these suggested that markers of receptivity are altered in women with unexplained infertility, delayed endometrial development or endometriosis. Some of these local factors have been shown to be necessary for implantation to occur in animal studies. PR modulators and PR blockers offer a tool to study the complex nature of endometrial receptivity. Furthermore antiprogesterone like mifepristone has been shown to be highly effective to inhibit endometrial receptivity and implantation.

Progestogen contraceptives are almost inevitably associated with disruptions in menstrual bleeding patterns. In many cases this amounts to bleeding that is frequent and/or prolonged. Evidence from studies of all available preparations suggests that menstrual disturbance is one of the most common reasons for discontinuation of these methods. This is particularly unfortunate since many progestogen users are women who have been unable to find other suitable methods and may now have very limited choices of safe contraception available to them. Currently, there is no effective long-term management for bleeding disturbances and effective and acceptable treatments are unlikely to be developed without a fuller understanding of the factors underlying this bleeding. Recent information has greatly advanced understanding of the vascular and endometrial changes associated with progestogen use, but a number of areas require further study before the mechanisms of BTB can be defined. In addition, further information is required from women using these preparations in developing and developed countries regarding the perception of bleeding disturbances and the relative tolerability of varying bleeding patterns and of amenorrhea.