The state of the pituitary-gonadal and pituitary-thyroid systems in women of reproductive age exposed to adverse occupational factors

The dissertation is devoted to the study of the neuroendocrine mechanisms of reproductive function disorders in women exposed to adverse occupational environmental factors. The research is focused on assessing the state of the pituitary-gonadal and pituitary-thyroid systems in female workers of paint-and-varnish and vibration-hazardous industries, as well as in patients with chronic intoxication by organic solvents. A comparative analysis was carried out of the frequency, structure, and clinical variants of disorders of the ovarian-menstrual cycle depending on the character of occupational exposure, the features of the hormonal profile (follicle-stimulating, luteinizing, and thyroid-stimulating hormones, estradiol, prolactin, testosterone, triiodothyronine, thyroxine, antibodies to thyroperoxidase) and the correlational relationships between clinical and hormonal indicators were studied. On the basis of the data obtained, additional criteria were suggested for the early diagnosis of hormonal disorders in working women, and the identification of risk groups for the development of reproductive function disorders and chronic intoxication was substantiated.

Relevance of the topic. In Russia, virtually every fifth worker is employed in conditions that do not meet sanitary and hygienic standards [Izmerov N.F., 2000; Sivochalova O.V., Radionova G.K., 1999]. According to data of the World Health Organization, 160 million cases of occupational diseases are registered annually worldwide, of which 30–40% become chronic and approximately 10% end in disability. A priority issue is the preservation of health in women exposed to adverse occupational factors. From the contemporary standpoint of occupational medicine and industrial ecology, the main risks to health, and to reproductive health in particular, are chemical and physical agents, as well as the heaviness and intensity of the workload, which constitute a real or potential danger for the development of disorders of reproductive processes [Knyazeva K.F., 1981; Nikitin A.I., 2005; Petrov-Maslakov M.A., Matysyak V.G., 1973, et al.]. The processes of population depopulation observed in recent decades largely determine the demographic and socio-ecological problems of society. In this connection, the development of programs for the medical and biological protection of the reproductive health of women working under harmful conditions, based on the study of the mechanisms of action of adverse factors, becomes important for the optimal implementation of the national project "Health" within the framework of additional medical assistance adopted by the President and the Government of Russia in 2005.

Occupational risk constitutes an integral part of the environmental risk affecting humans. The literature has accumulated sufficient evidence on the important role of stress-inducing systems in response to many ecological and occupational influences [Golikov Yu.N., 1989; Poteryaeva E.L., 1990; Sukharevskaya T.M., 1990]. The important role of the pituitary-gonadal and pituitary-thyroid systems under exposure to occupational vibration [Vlasenko V.V., 2005; Poteryaeva E.L., 1990], organic solvents [Shpagina L.A., 1994], and toxic-radiation exposure [Kirichenko O.V., 2005] has been demonstrated.

The effect of various chemicals on the state of the female reproductive system and on the childbearing function has also attracted attention. The early studies were predominantly of a clinical-statistical character. They examined the frequency of gynecological morbidity, primarily menstrual cycle disorders and fertility status, which serve as integral indicators of the response of the reproductive system to harmful exposures, as well as pathology of pregnancy and childbirth, and pathology of the fetus and the newborn. The bulk of the studies were devoted to the influence of products of the chemical, petrochemical, and rubber industries on the reproductive system of working women [Alipov V.I. et al., 1984; Elina V.A., 1980; Nikitin A.I., 2005; Petrov-Maslakov M.A., Matysyak V.G., 1973]. The authors showed that whereas inflammatory diseases of the pelvic organs predominated in women not in contact with chemicals, menstrual cycle disorders and pathology of pregnancy occupied the main place in female workers employed in chemical production.

Subsequently, an investigation was carried out into the state of specific functions, including the hormone-producing activity of the hypothalamus, pituitary, and gonads, in women employed in various branches of industry [Alipov V.I., Beskrovnaya N.I., Kosheleva N.G., Volkova Z.A., 1984; Elina V.A., 1980; Lytkin V.V., Antapova V.G., 1991; Popenko E.V., 2000]. Despite extensive hormonal studies of the menstrual function of female workers in various industries, there is still no unified view regarding the contribution of the components of the hormonal system to the development of occupational pathology. The hormonal support during the reproductive period remains insufficiently studied. Considering the inconsistency of data obtained by different researchers, the hormonal criteria and reserve capacities of the hypothalamic-pituitary and hypothalamic-thyroid systems have not yet been defined. The section concerning hormonal and clinical interrelationships requires further elaboration.

In view of this, in order to examine disorders of reproductive function, in particular disorders of the ovarian-menstrual cycle, the paint-and-varnish and vibration-hazardous industries were selected, which are characterized by exposure of the body to a complex of organic solvents and to vibration, respectively.

One of the mechanisms considered for the increased frequency of anemias in female workers in contact with organic solvents involves disorders of the ovarian-menstrual function of the hypermenstrual syndrome type against the background of dyshormonal changes in the neuroendocrine regulation of the pituitary-gonadal system [Alipov V.I., Volkova Z.A., 1983; Shpagina L.A., 1994].

Thus, both foreign and domestic literature devotes sufficient attention to the state of health, working conditions, and rational employment of women. At the same time, the hormonal relationships under exposure to chemical and physical factors have not been investigated in a comparative aspect with the involvement of general-adaptational hormonal systems, depending on the presence of disorders of reproductive function, in particular various variants of changes in the ovarian-menstrual cycle.

Aim of the study. To assess the state of the pituitary-gonadal and pituitary-thyroid systems under exposure to organic solvents and occupational vibration in women with disorders of reproductive function.

Objectives of the study:

1. To study the frequency and structure of disorders of the ovarian-menstrual function in women exposed to chemical (organic solvents) and physical (occupational vibration) factors, and in patients with chronic intoxication by organic solvents.

2. To study the state of the pituitary-gonadal system in women with disorders of the ovarian-menstrual cycle exposed to chemical and physical factors, and in patients with chronic intoxication by organic solvents (follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, testosterone).

3. To assess the state of the pituitary-thyroid system in women with disorders of the ovarian-menstrual cycle exposed to chemical and physical factors, and in patients with chronic intoxication by organic solvents (thyroid-stimulating hormone, free triiodothyronine, free thyroxine, antibodies to thyroperoxidase).

4. To study the clinical and endocrine interrelationships in women of toxic-hazardous and vibration-hazardous occupations and in patients with chronic intoxication by organic solvents with disorders of the ovarian-menstrual cycle.

Scientific novelty. On the basis of a clinical and hormonal examination (of the pituitary-gonadal and pituitary-thyroid systems), the neuroendocrine mechanisms have been refined and differences in disorders of the ovarian-menstrual function have been demonstrated in women working under harmful labor conditions. Under exposure to chemical (organic solvents) factors, disorders of the ovarian-menstrual cycle with a predominance of the hypermenstrual syndrome have been revealed. It has been shown that under exposure to physical (occupational vibration, noise) factors, disorders of the ovarian-menstrual cycle of the hypomenstrual syndrome type predominate.

In the state of the pituitary-gonadal system of women with disorders of the ovarian-menstrual cycle exposed to organic solvents and of patients with chronic intoxication, an increase in follicle-stimulating hormone and estradiol is observed, particularly in the hypermenstrual syndrome. Changes in the pituitary-thyroid system of these women have shown an enhancement of thyrotropic function with an increase in antibodies to thyroperoxidase, especially in the group of patients with chronic intoxication by organic solvents with disorders of the ovarian-menstrual cycle of the hypermenstrual syndrome type.

Under exposure to the vibration factor in women with disorders of the ovarian-menstrual cycle, a decrease in estradiol and prolactin with a simultaneous increase in thyroid-stimulating hormone has been noted in the hypomenstrual syndrome, and an increase in follicle-stimulating hormone, estradiol, and thyroid-stimulating hormone has been noted in the hypermenstrual syndrome.

As a result of correlation analysis, interrelationships between ovarian hormones and disorders of the ovarian-menstrual cycle have been revealed. Thus, in women of toxic-hazardous occupations with disorders of the ovarian-menstrual cycle of the hypermenstrual syndrome type, a direct correlation was revealed between the duration of menstruation and the levels of follicle-stimulating hormone, estradiol, antibodies to thyroperoxidase, thyroid-stimulating hormone, and length of service. In women of vibration-hazardous occupations with disorders of the ovarian-menstrual cycle of the hypomenstrual syndrome type, a direct correlation was revealed between the duration of menstruation and the levels of estradiol and prolactin, and an inverse correlation with thyroid-stimulating hormone and length of service.

Practical significance. Additional criteria for the early diagnosis of hormonal disorders in working women under exposure to chemical and physical factors have been developed. For women exposed to chemical occupational factors, the study of follicle-stimulating hormone, estradiol, thyroid-stimulating hormone, and antibodies to thyroperoxidase is recommended. For women of vibration-hazardous occupations, the study of prolactin, estradiol, and thyroid-stimulating hormone is recommended. Workers under conditions of high occupational risk should be monitored in risk groups for disorders of the ovarian-menstrual cycle and the development of chronic intoxication.

Statements for defense:

1. Disorders of the ovarian-menstrual cycle in women exposed to chemical occupational factors are characterized by a predominance of the hypermenstrual syndrome at 64.8% (in particular, hyperpolymenorrhea at 60%). Disorders of the ovarian-menstrual cycle in women of vibration-hazardous occupations include a high proportion of the hypomenstrual syndrome at 57.7% (in particular, hypomenorrhea at 44.2%).

2. The state of the pituitary-gonadal system in women with disorders of the ovarian-menstrual cycle exposed to chemical factors is characterized by an increase in follicle-stimulating hormone and estradiol. In women of vibration-hazardous occupations, by a decrease in prolactin and estradiol. The most pronounced changes in the pituitary-gonadal system were revealed in patients with chronic intoxication by organic solvents.

3. The state of the pituitary-thyroid system in women of paint-and-varnish production with disorders of the ovarian-menstrual cycle is characterized by an increase in thyroid-stimulating hormone and antibodies to thyroperoxidase. In women of vibration-hazardous occupations, an increase in thyroid-stimulating hormone has been revealed.