Endometrial vasculature in Norplant(R) users: preliminary results from a hysteroscopic study

Abstract

Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microvascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in vascular fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of vascular fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.

The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

“…BTB is thought to arise from superficial vessels within the endometrium which increase in number and fragility in Norplant users (Hickey et al 1996, Hickey & Fraser 2002. We also observed substantial changes in BV in the mouse model.…”

“…These include an increase in number and size of small endometrial blood vessels (BV) as well as an increase in microvascular fragility , Hickey et al 1996, Pritts et al 2005. Increased BV density was observed in the endometrium of women recently exposed to Norplant; however, the number of BV was not indicative of increased bleeding or spotting (Hickey et al 1999).…”

Progestogen only contraception and endometrial break through bleeding

“…Important hysteroscopic investigations of women complaining of BTB with both low and high dose progestogens have shown that bleeding occurs focally in the endometrium and originates from superficial, dilated vessels [23]. These vessels were also prone to contact bleeding during hysteroscopy.…”

Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives

“…In Norplant users, these vessels appear dilated and thin walled (Hickey et al 1996) and are increased in number in women with prolonged bleeding (Hickey & Fraser 2002). Furthermore, vessel support is decreased as observed by a decrease in perivascular smooth muscle a-actin .…”

“…Elevated numbers of some leukocyte populations and expression of matrix degrading enzymes, the matrix metalloproteinases, will also contribute to tissue fragility (Vincent et al 2002). Although the blood arises from the fragile blood vessels, it is clear that epithelial integrity must also be disturbed for vaginal bleeding to occur (Hickey & Fraser 2002) and indeed, sheets of easily detached surface epithelium are often seen at hysteroscopy (Hickey et al 1996) in users of P-only contraceptives, suggesting that the epithelium is fragile.…”