Protective effect of pregnancy for development of uterine leiomyoma

Abstract

Many factors that can modulate the risk of developing uterine leiomyoma have been identified, including parity. Epidemiological data on decreased risk of developing this disease has been subject to different interpretations regarding whether pregnancy per se is protective or, as leiomyomas are a major cause of infertility, women that develop these tumors are less fertile and thus have lower pregnancy rates. We have utilized an animal model genetically predisposed to uterine leiomyoma to investigate the potential protective effect of pregnancy on the risk of developing this disease. Female Eker rats that carry a mutation in the tuberous sclerosis 2 (Tsc-2) tumor suppressor gene develop uterine leiomyoma with a frequency of 65% when nulliparous. These animals were bred with intact or vasectomized males and tumor incidence determined after a single pregnancy (to confirm fertility) or multiple pregnancies over the lifetime of the animals. Females with multiple litters displayed a dramatic shift in tumor incidence and presentation. Tumor incidence decreased from 71% in single litter females to 10% in females that had multiple litters (average: five litters/animal). Interestingly, females bred with vasectomized males also exhibited a reduced tumor incidence of 41%, suggesting that the hormonal changes associated with early stages of pregnancy that occur in pseudopregnant females may have contributed to the protective effect of pregnancy.

Fibroid in pregnancy: characteristics, complications, and management

“…Another theory postulates that the vessels supplying fibroids regress during uterine involution postpartum, depriving them of their source of nutrition 25. The possible role of breastfeeding as an attributable factor due to its hypo-oestrogenic effect has not been robustly investigated clinically, but animal studies have ruled out this mechanism 26 27. In addition to parity, an age related chronological ‘critical size effect’ hypothesis has been put forward26: Pregnancy before 25 years may occur before the development of the fibroids, and conception after 30–35 years may be associated with already grown fibroids which may be too large to regress by the remodelling process.…”

Why is Parity Protective for Uterine Fibroids?

“…Furthermore, the pups were removed at birth so that breastfeeding could not explain the protective effect. 27 Mechanisms have not yet been explored in this animal model.…”

“…19 The plausibility of a biological basis for a protective effect of parity is supported by an experimental study conducted in Eker rats. 27 These animals, used as an animal model for fibroids, are heterozygous for a mutation in the tumor suppressor gene, tuberous sclerosis-2, and show a background incidence of uterine leiomyoma of 65%. This high incidence is found at 16 months of age among rats that have never bred.…”

Clinicopathologic study of large abdominal masses in gynaecological practice and their outcome

“…The preoperative diagnosis of ovarian cancer might reduce the need for repeat laparotomies and could lead to timely referral to gynaecological oncologists. [10][11][12][13][14][15] The aim of the present study is to find out the causes why these patients come with large abdominal masses, to find out the risk factors and to do proper management.…”