The Pathogenic Role of Vitamin D in Pelvic Pain Associated with External Genital Endometriosis
Study Objective: To enhance current knowledge about the pathogenesis of pelvic pain (PP) associated with external genital endometriosis (EGE).
Study Design: This was a cohort, prospective, comparative study with morphology.
Materials and Methods: One hundred and fifty women participated in this study. Patients with EGE (n = 120) were divided into two groups, each of which had two subgroups (A and B). Groups I and II consisted of women aged 20 to 41 (mean age 29.1 ± 3.3). Group I (n = 60) was comprised of patients with EGE complicated by PP: 30 women with 25(ОН)D deficiency in subgroup IA and 30 women without this deficiency in subgroup IB. Group II (n = 60) was made up of patients with EGE but without PP: 30 women with 25(ОН)D deficiency in subgroup IIA and 30 women without this deficiency in subgroup IIB. The control group consisted of 30 relatively healthy women without either 25(ОН)D deficiency, verified EGE, or PP, who had been referred for diagnostic laparoscopy to evaluate unexplained infertility.
Baseline total serum 25(ОН)D levels were measured by mass spectrometry in all participants. Other study examinations included morphology and immunohistochemistry with digital morphometry.
Study Results: The expression of vascular endothelial growth factor (VEGF) was significantly higher in biopsy samples from patients with PP and 25(ОН)D deficiency than in those from women with normal 25(ОН)D levels (77.4 ± 3.5% vs. 56.3 ± 2.8%; р < 0.05), which is a sign of increased angiogenesis. The expression of nerve growth factor (NGF) in both eutopic and ectopic endometrium was also significantly higher in subgroup IA than in subgroup IB (63.7 ± 2.1% and 47.3 ± 3.2% vs. 45.8 ± 1.9% and 36.1 ± 2.8%, respectively), which is a sign of enhanced neurogenesis. In women with PP and low 25(ОН)D levels, the rate of apoptosis (accompanied by abnormal expression of the vitamin D receptor [VDR]) was significantly lower (71.1 ± 3.7% vs. 31.5 ± 2.1%, p < 0.05). This conclusion was based on a lower expression of CASP3 in women with PP associated with 25(ОН)D deficiency, compared with those whose 25(ОН)D levels were normal (26.1 ± 1.5% vs. 28.4 ± 1.2%, respectively).
Conclusion: These findings suggest that in women with 25(ОН)D deficiency the proliferation/apoptosis balance in eutopic and ectopic endometrial cells shifts toward reduced apoptotic activity. The study also revealed impairment of 25(ОН)D metabolism in women with low levels of this vitamin. The same was true for the expression of VDR, a finding that supports the results of staining for VDR in the endometrium and endometrioma capsules of patients with EGE. This relationship underlies the key pathogenic mechanism involved in the development of PP in women with EGE, in whom the antiproliferative effects of vitamin D are reduced. These changes are accompanied by increased local neoangiogenesis and nerve fiber growth and a shift in the proliferation/apoptosis pattern toward inhibited apoptosis and increased proliferation.
M.R. Orazov — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. eLIBRARY.RU SPIN: 1006-8202. E-mail: email@example.com
M.B. Khamoshina — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. eLIBRARY.RU SPIN: 6790-4499. ORCID: http://orcid.org/0000-0003-1940-4534. E-mail: firstname.lastname@example.org
E.N. Nosenko — I.I. Mechnikov Odessa National Medical University, Ministry of Health of Ukraine; 2 Valikhovsky Pereulok, Odessa, Ukraine 65082. eLIBRARY.RU SPIN: 7601-2436. E-mail: email@example.com
A.O. Dukhin — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. eLIBRARY.RU SPIN: 8852-3114. E-mail: firstname.lastname@example.org
G.A. Demyashkin — I.M. Sechenov First Moscow State Medical University (Sechenov University), Russian Ministry of Health; 8/2 Trubetskaya St., Moscow, Russian Federation 119992. eLIBRARY.RU SPIN: 5157-0177. ORCID: http://orcid.org/0000-0001-8447-2600. E-mail: email@example.com
L.K. Barsegyan — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. E-mail: firstname.lastname@example.org
Yu.S. Chitanava — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. E-mail: email@example.comL.R. Toktar — Peoples’ Friendship University of Russia; 6 Miklouho-Maclay St., Moscow, Russian Federation 117198. E-mail: firstname.lastname@example.org
- Burney R.O., Giudice L.C. Pathogenesis and pathophysiology of endometriosis. Fertil. Steril. 2012; 98(3): 511–19. DOI: 10.1016/j.fertnstert.2012.06.029
- Оразов М.Р., Хамошина М.Б., Оразмурадов А.А., Кайгородова Л.А., Марапов Д.И., Барсегян Л.К. Уровень витамина D у женщин с эндометриоз-ассоциированной тазовой болью. Доктор.Ру. 2017; 9(138): 17–20. [Orazov M.R., Khamoshina M.B., Orazmuradov A.A., Kaigorodova L.A., Marapov D.I., Barsegyan L.K. Vitamin D Levels in Women with Endometriosisassociated Pelvic Pain. Doctor.Ru. 2017; 9(138): 17–20. (in Russian)]
- Доброхотова Ю.Э., Калиматова Д.М. Влияние витамина D на эндометриоз. Фарматека. 2018; 6(359): 84–8. [Dobrokhotova Yu.E., Kalimatova D.M. Vliyanie vitamina D na endometrioz. Farmateka. 2018; 6(359): 84–8. (in Russian)]
- Зазерская И.Е., Кузнецова Л.В., Дорофейков В.В. Витамин D и репродуктивное здоровье женщины: монография. СПб.: Эко-Вектор; 2017. 151 с. [Zazerskaya I.E., Kuznetsova L.V., Dorofeikov V.V. Vitamin D i reproduktivnoe zdorov'e zhenshchiny: monografiya. SPb.: Eko-Vektor; 2017. 151 s. (in Russian)]
- Cermisoni G.C., Alteri A., Corti L., Rabellotti E., Papaleo E., Viganò P. et al. Vitamin D and endometrium: a systematic review of a neglected area of research. Int. J. Mol. Sci. 2018; 19(8): E2320. DOI: 10.3390/ijms19082320
- Методика (метод) измерений массовой концентрации стероидных гормонов в пробах крови методом жидкостной хроматографии — тандемной масс-спектрометрии. МУ 08–47/376. Томск: ФГБОУ ВПО «Томский политехнический университет»; 2015. [Metodika (metod) izmerenii massovoi kontsentratsii steroidnykh gormonov v probakh krovi metodom zhidkostnoi khromatografii — tandemnoi mass-spektrometrii. MU 08–47/376. Tomsk: FGBOU VPO “Tomskii politekhnicheskii universitet”; 2015. (in Russian)]