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*Corresponding Author: Lesia Zhabitska. Assistant Professor Department of Obstetrics and Gynecology, Bogomolet`s National Medical University, Perinatal center, Kyiv, Ukraine. ORCID: 0000-0003-1797-4592
Citation: Lesia Zhabitska. (2022). Endocrine disorders and preterm labor. J Endocrinology and Disorders. 6(3): DOI:10.31579/2640-1045/119
Copyright: © 2022, Lesia Zhabitska, this is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 14 April 2022 | Accepted: 26 May 2022 | Published: 10 June 2022
Keywords: preterm labor; endocrine disorders; hormonal imbalance
Preterm labor remainsone of the most important problems in obstetrics and common public health problem.
It should be noted, that a large group of diseases associated with the development of prematurity are endocrine disorders and the share of various forms of endocrine disorders in pregnancy is increasing.
Research objective: to study the structure and frequency of endocrine disorder sin women with preterm labor.
Materials and methods. A retrospective study was conducted to study the structure and frequency of endocrine disorders in 2,426 women with preterm labor. Frequency of endocrine disorders were assessed,such as: hyperandrogenism (polycystic ovary syndrome(PCOS), non-classic сongenital adrenal hyperplasia (CAH), Cushing’s syndrome), thyroid disorders (hypothyroidism, auto immune thyroid disease, hyperthyroidism), hyperprolactinaemia, diabetes mellitus, including gestational diabetes mellitus; hyperparathyroidism.
Results. The study showed that endocrine disorders were observed in 37% of women with preterm labor (898 women out of 2,426 women with preterm labor).
In particular, 364 (15%) women with preterm labor had diabetes mellitus, including gestational diabetes mellitus, 339 (13,8%) - PCOS, 170 (7%) - non-classic congenital adrenal hyperplasia (CAH), 3 (0.12%) - Cushing's syndrome. Hyperprolactinaemia was observed in 267 (11%) women with preterm labor, hyperparathyroidism - in 2 (0.08%) women with preterm labor. Thyroid disorders occurred in 582 (23,9%) women with preterm labor.
Among women with preterm labor and thyroid disorders, the largest group was women with mild thyroid dysfunction, such as subclinical hypothyroidism, isolated hypothyroxinemia or TPOAb positivity - 379 (65%) women out of 582 women with thyroid disorders.
It is significant, that women with preterm labor most often had uncontrolled endocrine disorders, whether poorly controlled pre-conception or first diagnosed during pregnancy
- 503 (56%) women out of 898 women with ED.
Conclusions. The high frequency of endocrine disorders among women with preterm labor (37%), revealed in our study, indicates that today endocrine disorders remains an important factor of preterm labor.
In addition, results of our study showed, that among women with preterm labor and thyroid disorders, the largest group was women with mild thyroid dysfunction. It also implies that it is important to actively plan to assess early gestational thyroid function tests in women known to be thyroid disorders preconception.
It is significant, that women with preterm labor most often had uncontrolled endocrine disorders, whether poorly controlled pre-conception or first diagnosed during pregnancy. This should be considered when developing a strategy for the prevention of preterm laborand planning a pregnancy in women with endocrine disorders.
Preterm labor remainsone of the most important problems in obstetrics and common publichealth problem.
Despite numerous studieson the etiology and pathogenesis of preterm labor, the development and implementation of new medicines and ways to treat for this pathology, the frequency of preterm labor is not decreasing, occurring in 5 to 18 percent of births worldwide [1, 2, 3, 4].
Approximately 15 millionchildren are born prematurely everyyear [1].
Preterm labor is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age [3, 5]. Approximately 1 million childrendie each year dueto complications of preterm birth [6].
Many survivors face a lifetimeof disability, includingreduced renal function[7), neurodevelopmental impairments [8], cerebral palsy [9], visual, hearing problems and reducedmyocardial function [10].
Globally, prematurity is the leading cause of death in children under the age of 5 years [1].
Prematurity is also a major socio-economic problem. In addition to intensive neonatal care, most premature infantsrequire long-term medicalcare at high financial cost.
Despite being a common public health problem, the causes of preterm labor are largely unknown.
Recently, many authors attach particular importance to the concept of heterogeneity of causes of prematurity, pointing out that preterm labor can be caused by a large number of direct and indirect factors [11]. We support this statement, given our recent research, including our analysis of women with pretermlabor.
However, it should be noted, that a large group of diseasesassociated with the development of prematurity are endocrine disorders (ED).
As our experience shows, in obstetric practicerecently among the diseases that complicate the course of pregnancy and delivery, the share of various forms of ED is increasing.
It is known that the endocrine system plays an important role in the gestational process [12, 13]. During pregnancy, there are close hormonal relationships between the mother
and fetus. The development of a new endocrine complexof mother-placenta-fetus provides the physiological course of pregnancy. ED in a pregnant woman has an adverse effect on her health, is a cause of complications during pregnancy and childbirth, and is a high-risk factor for preterm labor [13]. Therefore, understanding the impact of hormonal disorders on the prolongation of pregnancy and the condition of the fetus, the role of EDin the development of prematurity could shed light on the mechanisms associated with preterm labor andreduce their frequency.
Hormones of special interest during pregnancy should be conditionally divided into two categories: reproductive hormones (estriol, progesterone, testosterone and sex hormone bindingglobulin (SHBG)) and thyroid hormones.
Based on currentdata, the followingmechanisms of adverseeffects of hormonaldisorders on the prolongation of pregnancy should be considered.
Increasing levels of testosterone
May reduce levelsof endometrial secretoryproteins which are positively associated with length of gestation [14].
May act antagonistically with estrogens [15].
Testosterone circulates through the body bound to SHBG, so changingSHBG concentrations couldaffect the concentration of bioavailable testosterone.
Estriol and progesterone imbalance
It’s critically importantfor the timing of labor, as estriolprimes the uterus for contractions [16] and progesterone promotes quiescence of the uterus until the time of labor [17].
Progesterone concentrations increase during pregnancy, contributing to uterine quiescence, downregulation of prostaglandin production, and immune tolerance of the fetus [17]. At the beginningof labor, the concentration of progesterone is not significantly reduced; rather, the body's response to progesterone is suppressed. It isunclear exactly how this occurs,but possibly includedecreasing in progesterone receptor expression, changes in receptor isoforms, and local progesterone metabolism [18].
As term approaches, the ratio of progesterone to estriol changesin favor of estrogen, and a functional decrease in progesterone stimulates the onset of labor. The new dominance of estrogen increases prostaglandin and oxytocin receptors and enzymes responsible for muscle contraction, which together promote delivery [19].
Progesterone keeps the effectsof estriol under control during pregnancy, but the untimely transition of dominance from progesterone to estriol can lead to preterm labor [20].
Thyroid hormones.
Numerous clinical studieshave convincingly demonstrated that thyroid hormones,synthesized in sufficient quantities, support optimal prolactin production, monoamine synthesis, corpus luteum activity and, thus, ensure the normal functioning of the gonads, the possibility of pregnancy and its physiological course to term of labor, play an important role in the normal development of thefetus [21].
There is a close relationship between the reproductive and thyroid systems[22, 23, 24].
First, they ha
ve common central regulatory mechanisms - thyroliberin stimulates not only the secretion of thyroid-stimulating hormone(TSH), but also prolactin.
Secondly,there is a structural homologyof luteinizing hormone(LH), follicle- stimulating (FSH) hormone, human chorionic gonadotropin (hCG) and TSH. The structural α-unit is common to all these hormones and only the β-subunit is specific to each of them. This allows, in particular, hCG to bind to TSH receptors. Increased production of hCG causes an increasein free thyroxine (fT4) and, consequently, suppression of TSH.
In addition, estrogensstimulate the synthesisin the liver of not only sex steroid- binding, but also thyroid-binding globulins. Changes in the levels of these proteins are important in the pathogenesis of reproductive dysfunction.
Also, experimental studiesrevealed the presenceof receptors for TSH and triiodothyronine (T3) in the ovaries (oocytes and granulosa cells). This means, that thyroidhormones act unidirectionally with FSH at the cellularlevel. And thyroid dysfunction has a direct impact on steroidogenesis, ovulationand corpus luteum function, quality and viability of embryos.
Сorticotropin releasinghormone (CRH)
Сorticotropin releasing hormone, which is secreted from the hypothalamus and normally involved in stress response, may also be key in understanding the endocrine role in preterm labor. CRH concentrations are low in the first half of pregnancy and then begin to exponentially increase around the 20th week of gestation to peak at birth [25]. An earlier and more rapid increase of CRH concentrations has been observed in women who experience preterm labor [26, 27], suggesting that CRH may be involved in a «placental clock» [28]. CRH receptors are present in the myometrium and in the fetal zone of the fetal adrenal gland, so CRH could exert its effects on labor by interacting with thesereceptors [25].
To study the structureand frequency of endocrine disordersin women with preterm labor.
We conducted a retrospective study to research the structure and frequency of endocrine disorders in 2,426 women with preterm labor.
The study group included women who gave birth prematurely in the period from January 2018 to November 2021 in the Perinatal Center of Kyiv (Ukraine).
We evaluated spontaneous preterm labor, defined as labor that starts before 37 weeks of pregnancy, presenting with premature rupture of membranes, spontaneous preterm labor, or both[29].
Gestational age was calculated on the basis of recommendations from the American College of Obstetricians and Gynecologists, self-reported date of the last menstrualperiod (LMP) was collected at the first study visit and used in combination with early ultrasound measurements to determine gestational age at birth [30]. Briefly, the LMP was used as the gold standard and was compared to ultrasound measurements taken primarily before 14 weeks gestation. Gestational age was changed from the LMP estimate to the ultrasound estimate if the difference between the two methods was greater than a certain numberof days, depending on which week the ultrasound was performed.
All women agreedto participate in the study.
In the study group of women with preterm labor evaluated the frequency of ED, such as: hyperandrogenism (polycystic ovary syndrome (PCOS), non-classic сongenital adrenal hyperplasia (CAH), Cushing’s syndrome), thyroid disorders (hypothyroidism, autoimmune thyroid disease,hyperthyroidism), hyperprolactinaemia, diabetesmellitus,including gestational diabetesmellitus; hyperparathyroidism. Researchresults were adjustedfor maternal age, education, parity,marital status, alcoholconsumption, smoking and year of delivery.
Our results showed that endocrinedisorders were observed in 37% of women with pretermlabor (898 women out of 2,426 women with preterm labor).
The structure of ED in women with preterm laborwas analyzed (Table 1).
In particular, 364 (15%) women with preterm labor had diabetes mellitus, including gestational diabetes mellitus, 339 (13,8%) - PCOS, 170 (7%) - non-classic congenital adrenal hyperplasia (CAH), 3 (0.12%) - Cushing's syndrome. Hyperprolactinaemia was observed in 267 (11%) women with preterm labor, hyperparathyroidism - in 2 (0.08%) women with preterm labor.
Thyroid disorders occurred in 582 (23,9%) women with preterm labor (Table 1). Within this cohort, 151 women (26%) had clinical hypothyroidism, 221 women (38%) had subclinical hypothyroidism, 76 women (13%) had isolated hypothyroxinemia and 82 (14%) had thyroid peroxidase antibody (TPOAb) positive (Figure1). Hyperthyroidism occurr edin 52 (9%) women with thyroid disorders (Figure1).
Thus, among women with preterm labor and thyroid disorders, the largest group was women with mild thyroid dysfunction, such as sub clinical hypothyroidism, isolated hypothyroxinemia or TPOAb positivity - 379 (65%) women out of 582 women with thyroid disorders.
These findings validate,that mild thyroiddysfunction, such as subclinical hypothyroidism, isolated hypothyroxinemia and TPOAb positivity in pregnant women are also risk factors for preterm labor.
It implies that it is important to actively plan to assess early gestational thyroid function tests in women known to be thyroid disorders preconception.
In addition, it is significant, that women with preterm labor most often had uncontrolled endocrine disorders, whether poorly controlled pre-conception or first diagnosed during pregnancy- 503 (56%) women out of 898 women with ED.
The high frequency of endocrine disorders among women with preterm labor (37%), revealed in our study, indicates that today ED remains an important factor of preterm labor.
In addition, results of our study showed, that among women with preterm labor and thyroid disorders, the largest group (65%) was women with mild thyroid dysfunction, such as subclinical hypothyroidism, isolated hypothyroxinemia or TPOAb positivity.
It also implies that it is important to actively plan to assess early gestational thyroid function tests in women known to be thyroid disorders preconception.
It is significant, that women with preterm labor most often had uncontrolled endocrine disorders, whether poorly controlled pre-conception or first diagnosed during pregnancy. This should be considered when developing a strategy for the prevention of preterm laborand planning a pregnancy in women with endocrine disorders.
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