Progestogen only contraception and endometrial break through bleeding

Abstract

Progestogen only contraceptives (POC) provide a safe and effective method of fertility regulation. Unfortunately, they are commonly associated with the problem of endometrial break through bleeding (BTB), often leading to discontinuation of use. An increase in endometrial vascular fragility has been demonstrated as an important mechanism that contributes to BTB but our understanding of the interaction between exogenous steroid use and endometrial vasculature remains incomplete. This review sets out to describe a number of commonly used POC, their effects on endometrial morphology and possible molecular and cellular mechanisms that may lead to unscheduled bleeding.

A review of the endometrial histologic effects of progestins and progesterone receptor modulators in reproductive age women

“…Both etonogestrel and levonorgestrel have similar endometrial histologic findings after 12 months of use [33]. Levonorgestrel implants result in an increased density of dilated, thin-walled fragile blood vessels that lead to the early onset of unscheduled bleeding [25].…”

“…There are no consistent histologic features that allow differentiation between the endometrial and vascular effects of the various 19-nor steroids [25]. The 17-alpha-acetoxyprogesterone derivatives, when used alone, tend to produce similar but less prominent progestational effects than those of the combined 19-nor steroids with ethinyl estradiol estrogen.…”

“…Endometrial changes that occur with progestin-only therapy are highly variable and depend on dose, type of progestin, duration of therapy, the degree of inhibition of follicular activity and whether or not ovulation occurs. The vascular changes are significant in that progestin-only implants have more superficial blood vessel fragility resulting in unscheduled breakthrough bleeding [25].…”

Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell–derived factor 1 in human endometrial stromal cells

“…Dienogest (DNG) is considered to be a new progestin that combines the properties of both a 19-nortestosterone derivative and a P derivative. Progestins are suggested to enhance blood vessel fragility in the endometrium and to change locally in terms of structural integrity, tissue perfusion, and local angiogenic factors (17,18). On the endometrium, locally released progestins produce with time a suppression of the proliferative activity, diffuse predecidual reaction in the stroma, and change leading to the poor development of glands (16).…”

Using phytoestrogens as aprophylaxis against irregular uterine bleeding possibly occurring while using Depot-medroxyprogesterone acetate (DMPA) as a contraceptive method

“…(13) Since there are no established long-term interventions available to manage unscheduled bleeding, a greater understanding of the mechanisms involved is required.…”