Treatment algorithm for uterine leiomyoma for women of reproductive age taking into account genetic factors
Authors: Kornatska А.G. , Flaksemberg M.A. , Borysiuk O.Y. , Chubei G.V. , Rossokha Z.I. 
Published: July 2021

The objective: to determine the association of estrogen receptor gene polymorphisms ESR1 and progesterone PGR with the development of uterine leiomyoma (UL) and to develop a patient management algorithm based on the results of ultrasound and genetic studiesMaterials and methods. Comprehensive examination was made for 90 women with intramural myoma in the age from 26 to 45 years, which additionally included determination of the presence of the Progins polymorphism of the PGR gene and polymorphic variants A351G and T397C of the ESR1 gene. Further treatment depended on the polymorphisms of the studied genes, the number and size of myomatous nodules (MN) and their position in relation to the uterine cavity.Results. Minor alleles for the estrogen receptor gene ESR1 T397C were detected in 87.2% of women with MN over 40 mm in diameter, while they were 54.2% in women with MN less than 20 mm (p<0.05). The minor alleles of ESR1 gene locus A351G were also significantly more common in women with large MN compared to LU less than 20 mm – 69.2% versus 37.5% (p<0.05). The polymorphism of the progesterone receptor regulator gene PGR Progins was found in 33.3% of patients with small size LU and from 7.7% to 18.5% in women with large LU and MN larger than 20 mm in diameter at ultrasound.Treatment was started with hormonal therapy and in the presence of the T1/T1 genotype of the PGR Progins gene and the absence of endometrial hyperplasia according to histological examination, was prescribed hormonal therapy with mifepristone 50 mg daily for 3 months, followed by monitoring of the course of the disease.GnRH agonists were prescribed as preoperative preparation in the case of detection of PGR Progins gene polymorphisms (T1/T2 or T2/T2 genotypes), endometrial hyperplasia and MN over 40 mm. In the case of small nodules that do not deform the uterine cavity and an ESR1 gene reference genotype, contraceptive OCs were recommended for six months or more to stabilise LU growth. MN over 30 mm distorting the uterine cavity and the presence of ESR1 minor alleles of the oestrogen receptor gene were the grounds for surgical treatment of such an LU.As a result of this approach, the incidence of pain syndrome decreased by almost 4.7 times, menstrual disorders in the form of hyperpolymenorrhoea and AUB by 8 times. An improvement in general well-being was subjectively reported by 64.4% of the patients, «without change» – by 24.4% of the patients. Only 11.1% of women reported a worsening of subjective sensations, which was associated with the side effects of therapy. The size of the lymph nodes decreased considerably in 44.4% of the patients, a partial effect was noticed by 26.7% of the women. There was observed no growth of the nodes in the patients during treatment or after it. A pregnancy occurred in 68.5% of the patients and ended in childbirth in 86.5% of cases.Conclusion. Consideration of the patient’s genetic status contributes to the improvement of LU treatment outcomes. The most effective is to prescript mifepristone in patients with MN under 40 mm, including multiple ones, when the operation is associated with a high risk. In the case of larger mets (over 50 mm), hormonal therapy is less effective and can be used for preoperative preparation. This approach allows to control symptoms and reduce the size of the node in 72.2% of patients and in 68.5% of cases the pregnancy can be achieved.