Effects of progestin-only contraceptives on the endometrium

ABSTRACT

Introduction

The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation.

Areas covered

Mechanisms involved in the progestin-induced endometrium desynchronization are individually reviewed for each of the routes of administration and, whenever possible, by individual members of the various families of synthetic progestin derivatives.

Expert opinion

For contraceptive purposes, progestins are today administered through several routes: orally, as injections, subdermally and via the vagina or the uterine cavity. Given this variety of modalities, their effects may differ, depending on the route of administration, concentration reached at the level of the endometrium and the duration of use. These are characterized by inactivation of the endometrium.

Progestin-only contraception provides a safe and effective control of fertility regulation, although, they are associated with the problem of endometrial break through bleeding that may lead to discontinuation. Unfortunately, in spite of a major research effort over two decades, there is not, as yet, an established long-term intervention available to manage bleeding irregularities, making mandatory a deeper understanding of the mechanisms involved is required.

KEYWORDS:

• Progestin only contraceptives
• progestin only oral contraceptives
• injectable contraceptives: intrauterine system
• subdermal implant
• endometrium

Article highlights

• Progestins, most commonly utilized for contraception, differ in their biological action, and this is reflected also in their effect on the endometrium.

• Contraceptive progestins are administered through several routes: orally, as injections, sub-dermally and via the vagina or the uterine cavity; their effect will often differ, depending on the route of administration, the concentrations reached at the level of the endometrium and the duration of use.

• When progestins are administered orally, the thickness of the endometrium is progressively reduced in relation to the duration of treatment; there is a variable decrease in the size of the spiral arteries; glands are reduced in number, their epithelium usually appears atrophic and well-preserved glands coexist with atrophic ones.

• Two injectable preparations are today utilized as long-acting progestin-only contraceptives: DMPA and NET-EN. They produce endometrial changes characterized by the presence of low cuboidal cells with sparse distribution of low columnar cells, glands with atrophic changes and compact uterine stroma, with or without patches of edema.

• Three types of LNG-IUS have been developed, containing 13.5, 19.5, and 52 mg, respectively. All three produce very similar progestogenic effects on the endometrium, although the first two result in a lower systemic exposure to LNG and lower incidence of anovulation.

• Most of the investigations on the LNG-IUS have been carried out with the system containing 52mg and releasing 20μg daily.

• The 2 long-acting subdermal implants marketed today, reduce endometrial thickness and induce an inactive, or weakly proliferative endometrium.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer declarations

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.