Uterine Fibroids and Progestogen Treatment: Lack of Evidence of Its Efficacy: A Review

Abstract

Background: The objective of this review is to determine the evidence or, conversely, the absence of evidence regarding the effectiveness of progestogens in treating premenopausal women with uterine fibroids. In particular, the goal is to address recurring questions as to whether they are effective or not for managing symptoms commonly attributed to fibroids.

Methods: A review of the most relevant papers (n = 63) on the efficacy of progesterone and progestogens as medical therapy for uterine fibroids.

Results: Having reviewed the most significant papers on the relationship between uterine fibroids and progesterone/progestogens, it is clear that there is biochemical, histological and clinical evidence that progesterone and progestogens play a critical role in the pathogenesis of myomas.

Conclusion: Since progesterone is already implicated in the pathogenesis of this entity, using progestogens to manage fibroids is like constantly adding fuel to the fire, rendering this treatment ineffective.

Keywords: GnRH agonist; GnRH antagonist; add-back therapy; heavy menstrual bleeding; progesterone; progestogen; uterine fibroids.

Figure 1

Article disposition flow diagram: The following keywords were used: uterine fibroids, progesterone, progestogen, GnRH agonist, GnRH antagonist, heavy menstrual bleeding, add-back therapy. Two hundred and fifty-six records were identified. After duplicate removal, 140 records were screened, of which only peer-reviewed articles focusing on the subject were considered for eligibility assessment (n = 63). Among the conducted studies, specific various criteria led to the exclusion of 22 papers due to duplicated results.

Figure 2

Schematic illustration of autocrine and paracrine mechanisms activated by estrogen receptor alpha (Era) and progesterone receptors (PRs) in uterine leiomyoma cells. Estradiol (E2) arrives with the blood supply (endocrine), but is also synthesized within cells (autocrine), from precursors such as testosterone and estrone (E1). ERa may be phosphorylated (P) by kinases and interact with estrogen response elements (EREs) in the nucleus. 178HSD1: 178-hydroxysteroid dehydrogenase type 1; MAPK: mitogen-activated protein kinase: PDGF: platelet-derived growth factor; P13K: phosphatidylinositol-3-kinase; AKT: serine/threonine protein kinase: Bcl-2: B-cell leukemia/lymphoma-2 protein; KLF: Kruppel-like transcription factor 11; TGF-83: transforming growth factor beta 3;EGP: epidermal growth factor; ECM: extracellular matrix; Prog: progesterone; R: progesterone receptor in the cytosol and PRE: progesterone response element. From Reis et al. Best Practice & Research, Clinical Obstetrics and Gynaecology (2015), with permission from the editor and author.