RU2367954C1 - Method of dermatosis development prediction in women with scleropolycystic ovarian syndrome (spco) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology and concerns method of dermatosis development prediction in women with scleropolycystic ovarian syndrome (SPCO). Method consists in venous blood analysis for leptine level on 3-5th day of independent or induced menstrual cycle. If At leptine level is 12.6 ng/ml and higher, acneiform rash and facial and scalp seborrhea oleosa are predicted.

EFFECT: enabled early prediction of dermatosis development in SPCO women.

3 ex

Description

The invention relates to medicine, namely to dermatovenerology, and can find application in the clinic of skin diseases to predict the occurrence of acne and oily seborrhea of the face in women with PCOS.

The causes of skin diseases are extremely diverse and complex. The skin is constantly exposed to external influences, including infectious (bacteria, viruses, protozoa, fungi, etc.), which can cause abnormal changes in it. On the other hand, the skin is closely connected with the internal organs and therefore their disease can also cause a pathological process. In the development of skin lesions, individual predisposition, the degree of body resistance, as well as social factors - working and living conditions / copyrighted www.policlinica.ru/ are extremely important.

The condition of the skin is often directly related to reproductive function. With severe cosmetic skin defects, many women develop neurotic conditions that indirectly affect the state of the reproductive system. Thus, a study by I.V. Kondratenko (2001) showed that the long course of acne (acne) and their irrational treatment in young women caused pronounced psychological changes, which in turn exacerbated the course of other diseases. Today it became known that many aspects of the condition of the skin are associated with the metabolism of hormones, in particular, the lack of production of estrogen and increased production of androgens, so the possibilities for treating skin diseases have expanded significantly.

It was revealed that not only acne, but also some other skin defects that may bother a woman are androgen-dependent. The activity of the sebaceous glands is determined by several factors: gender, age, environment, state of the endocrine, nervous, reproductive systems, etc. (S.I. Rogovskaya, 2003).

Polycystic ovary syndrome (PCOS) is one of the main causes of hyperandrogenism and impaired reproductive system function. The high frequency of endocrine-metabolic disorders and anovulatory infertility among patients with PCOS, as well as the frequent lack of effect from the use of ovulation inducers, leads to the search for alternative drug-resistant ways to restore fertility. The close relationship of insulin resistance (IR) and hyperinsulinemia (GI) with the formation of PCOS, proved by a large number of scientific studies, was the theoretical basis for a new direction in the conservative treatment of patients with PCOS by using insulin sensitizers (IS) - drugs that increase tissue sensitivity to insulin and reduce GI (Hasan JA, GUMemon. Impact of metformin therapy in pacients with polycystic ovary syndrome // Coll Physicians Surg Pak. 2005. Vol.15. No. 11. P.712-715 .; Yilmaz M. et al. The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrom e // J. Endocrinol. Invest. 2005. Vol. 28. No. 11. P.1003-1008).

The results of hormonal studies revealed the most typical biochemical criteria for polycystic ovaries, independent of BMI: an increase in LH level of more than 10 IU / L in 67.5% of patients, an increase in LH / FSH ratio of more than 2.5 in 72.3% of patients and an increase in concentration total T more than 2.5 nmol / l - in 63.2% of patients (Metabolic disorders in patients with polycystic ovary syndrome. // Journal of Reproduction Problems. - 2000. - No. 6).

Seborrhea is a disease caused by a disorder of fat formation, manifested by increased secretory activity of the sebaceous glands and a change in the chemical composition of sebum. Sebum secretion disorder usually occurs as a result of a disturbance in the physiological balance between estrogen and androgen hormones in the direction of the latter, which is more often observed between the ages of 14 and 25. The diagnosis of seborrhea is based on the clinical picture. In unclear cases, the differential diagnosis is carried out with seborrheic eczema, psoriasis.

Rosacea (more precisely, the papulopustular stage of rosacea) is a chronic relapsing disease of the skin of the face. Women after menopause are more likely to get sick. The disease is promoted by a number of endogenous factors: disorders of the gastrointestinal tract (especially gastritis), endocrine disorders in the form of ovarian dysfunction, menopause, and also vegetovascular dystonia. The diagnosis is made on the basis of the clinical picture; in doubtful cases, histological data are used. The differential diagnosis is carried out with acne vulgaris, lupus erythematosus.

Acne vulgaris (Acne vulgaris; syn. Acne juvenile) - a chronic, often recurring purulent inflammation of the sebaceous glands. A favorable background condition for the development of acne is usually seborrhea. Increased sebum, which develops primarily due to an increase in the concentration of androgens and / or a decrease in the blood content of androgen-binding protein, leads to keratinization of the mouth and ducts of the sebaceous glands, hypertrophy of the sebaceous glands and the appearance of comedones - blackheads. The development of acne vulgaris is promoted by a hereditary predisposition, dysfunctions of the endocrine glands, digestive tract pathology, hypovitaminosis, and dietary disorders. The diagnosis is based on the clinical picture. To confirm the diagnosis, you can use the results of a histopathological study. The differential diagnosis is carried out with a pustular stage of rosacea, pustular acne syphilis (Oleg Leonidovich Ivanov. “Skin and sexually transmitted diseases”, 2006).

Methods for diagnosing skin diseases: instrumental (examination under a Wood fluorescent lamp, determination of dermographism, Nikolsky, Benier-Meschersky symptoms, probe, apple jelly, symptom triad, Köbner isomorphic reaction, staging of Balcer iodine test, allergic skin tests, bacterioscopic, bacteriological, histological cytological, immunological, general clinical methods (A.S. Nesterov, 2006).

A known method for the diagnosis and photodynamic therapy of acne (acne vulgaris) (RF patent No. 2265463, 2005.12.10). According to this method, diagnostics are carried out using fluorescence spectra of the affected areas. Areas with intrinsic fluorescence are irradiated with light with a wavelength of 630 ± 10 nm and an energy density of 10-4500 J / cm ² , an applicator containing a 2-20% solution of 5-aminolevulinic acid is applied to areas that do not have intrinsic fluorescence, and after exposure and removal of the applicator is irradiated with light with a wavelength of 630 ± 10 nm and an energy density of 10-4500 J / cm ² . The progress of the irradiation process is monitored by recording the fluorescence spectra on the affected areas of the skin before irradiation, after applying an applicator containing 5-aminolevulinic acid, after irradiation, and irradiation was stopped when the concentration of porphyrins was lower than therapeutic values.

A known method of electrodiagnosis of the degree of damage to the skin with dermatoses (RF patent No. 2201135, 2003.03.27). The method consists in the fact that the test object is placed between the active and indifferent electrodes, an electric field is formed between the electrodes by applying a constant high voltage of 30-50 kW to them, and finely dispersed biologically neutral white powder is sprayed onto the skin of the test object for 10-30 s tone charged by the electric potential of the active electrode, disconnect the electrodes from the high voltage source and assess the degree of damage to the skin by the topography of the races definiteness powder, said powder deposition is performed in pulsed mode.

A known method for predicting the course of pyoderma (RF patent No. 2258220, 2005.08.10). The method is carried out by isolating from the focal zone of pure cultures of Staphylococcus aureus and Staphylococcus epidermidis, determining their antilysocyme activity. With indicators of the level of antilysocyme activity below 4.5 ± 0.5 μg / ml, an acute course of pyoderma is predicted, with indicators of antilysocyme activity above 6 ± 0.5 μg / ml, a chronic course of pyoderma is predicted.

The study of the role of leptin in patients with PCOS is of great interest, since this pathology is often accompanied by obesity and IR, independent of body weight.

As a result of the study, it was found that leptin levels progressively increased with increasing body weight. If in women with normal body weight it reached a value of 8.638 ng / ml, in women with overweight - 16.52 ng / ml, then in women with obesity - 17.1 ng / ml (Orlov V.I., Sagomonova K .Yu., Kuzmin A.V., Zinkina E.V., Kaushanskaya L.V. “LEPTIN, FREE AND GENERAL TESTOSTERON IN PATIENTS WITH PCOS” // Actual issues of obstetrics and gynecology: journal of the Russian Association of obstetrician-gyne. - 2001/2002. - T.1, No. 1 // Actual issues of obstetrics and gynecology (Electronic resource): journal of the Russian Association of Obstetricians and Gynecologists - 2001/2002. - T1, No. 1. Access mode: http: / /gyna.medi.ru/ag12.htm - 03/25/08).

Leptin indices were also analyzed depending on the presence and type of obesity, the duration of anovulation, the nature of menstrual irregularities, the presence of HI and IR, and the echographic type of polycystic ovaries. It is known that the male type of obesity is characterized by more pronounced metabolic disorders (Pasquali R., Vicennati V., Gambineri A. Influence of weight and distribution of adipose tissue in functional hyperandrogenism. Contracept Fertil Sex 1998; 26: 5: 372-375). The leptin level in 11 patients with male type of obesity was in the range of 3.95-36.8 ng / ml and averaged 14.9 ± 1.5 ng / ml, which was significantly higher than the concentration of this hormone in the blood serum (9 , 43 ± 1.15 ng / ml) 12 patients with a female type of obesity. T.O. the leptin concentration in patients with PCOS with excess body weight (BMI greater than 25) is significantly higher in the male type of obesity (T / B greater than 0.85). (M.A. Gevorgyan, N.E. Kushlinsky, I. B. Manukhin “The role of leptin in polycystic ovary syndrome.” Department of Obstetrics and Gynecology, Faculty of Medicine with a course of FPDI MGMSU, Moscow // Journal of Reproduction Problems. - 2000 . - No. 6).

A common drawback of the methods analyzed in the patent and medical literature is that they do not allow early diagnosis or prediction of skin pathology in women with PCOS at an early stage of the disease in order to take preventive measures.

The present invention solves the problem of increasing the effectiveness of early diagnosis and prediction of the occurrence of acne and oily seborrhea in women with PCOS.

The problem is solved in that for women with PCOS on the 3-5th day of an independent or induced menstrual cycle, a hormone test is performed, the level of leptin in the venous blood is determined and, in the presence of an indicator exceeding 12.6 ng / ml, the development of skin lesions is predicted, namely, acne and oily seborrhea of the face and head.

The technical result is the possibility of obtaining objective data on the development of skin lesions by the pathological process by the hormonal method of examination. The inventive method improves the efficiency of early diagnosis of skin pathology, the definition of a strategy for the treatment of skin diseases in women with PCOS.

The skin is very sensitive to the effects of female sex hormones (as well as to androgens) due to the specialized receptors available in it. Estrogens inhibit the secretory activity of the sebaceous glands, but practically do not affect the apocrine glands, increase the level of hyaluronic acid in the dermis, respectively increasing the water content, participate in the slow conversion of soluble collagen into an insoluble form, and also stimulate epidermal melanogenesis, which explains the transient hyperpigmentation that occurs before menstruation , especially in the eyes and nipples; during this period, hair growth slows down. Estrogens have anti-inflammatory properties and reduce the skin response in a delayed-type hypersensitivity reaction (S.R. Utts, O.D. Odoevskaya. “Morphofunctional features of female skin.” - Laboratory of Photobiology and Photomedicine of the Saratov Research Institute of Hygiene in the Ministry of Health of the Russian Federation // Bulletin of Dermatology and Venereology , 3-1999, pp. 8-13).

Persistent acne in a woman can be a sign of excessive production of androgens (male sex hormones). The most common cause of androgen excess in women is polycystic ovary syndrome (PCOS). In this disease, the ovaries are many cavities filled with fluid and not containing eggs. Women with PCOS tend to have fertility problems.

Like acne, very oily skin can be a sign of hormonal imbalance in the form of high levels of androgens in the blood. High levels of androgens are often caused by polycystic ovary syndrome (PCOS).

An important role in increasing fat production is played by hyperandrogenism, one of the symptoms of which may be seborrhea. Seborrhea is considered as a skin disease in which there is excessive fat formation and a change in the composition of the sebaceous secretion due to the accumulation of a large amount of free fatty acids. In addition to hyperandrogenism, the development of seborrhea is affected by stress, gastrointestinal pathology, lack of vitamins, and other somatic diseases that affect the quality and quantity of sebum. With seborrhea, the bactericidal properties of the water-lipid film are suppressed, sebum accumulates in the ducts of the glands and on the surface of the skin, creating the conditions for the development of pyococcal and other infections. Following this, acne develops.

Acne (acne) is currently considered a polymorphic multifactorial disease of the hair follicles and sebaceous glands. In acne etiology, in addition to hyperandrogenism, lipid imbalance, an increase in the pathogenicity of pathogens such as Propionibacterium acne (P. acne), Staphylococcus epidermidis and other cocci, lipophilic yeast type Pitirospporum (P. ovale et orbiculare) and disruption of keratinization processes also play an important role.

However, an obstetrician-gynecologist often has to deal with erased forms of hyperandrogenism, which play an important role in the genesis of infertility, menstrual dysfunction, miscarriage or other reproductive system pathology in women, while the most obvious symptoms of hyperandrogenism are manifested by the skin.

The production of androgens from cholesterol is carried out in women by the ovaries, adrenal glands and, to a greater extent, by transformations in other organs (in particular, in the liver, skin, adipose and muscle tissues). The androgenic effect is realized only if the androgen-androgen receptor reaction occurs and the corresponding complex is formed. Interacting with the genome inside the nucleus, this complex initiates a specific cellular response, which is expressed in a cascade of various metabolic processes. For example, fat is produced in the sebaceous gland of the skin as a result of exposure to the androgen receptor complex. Antiandrogens, connecting with the receptor, form only a suboptimal complex and block further transformation and the cellular response.

Thus, it is important to emphasize that in certain pathological conditions leading to androgenization, not only quantitative shifts in the synthesis of hormones are detected, but their qualitative nature also changes with the predominance of certain metabolites with different properties.

In general, the clinical manifestations of androgenization and subsequent treatment are determined by its causes, the main of which are ovarian (the most common ovarian pathology is their polycystosis - PCA, which is currently considered as a polyglandular, polyetiological, polysymptomatic pathology). It is important to remember that 46% of women with PCA have a combined form of hyperandrogenism (27% predominantly ovarian, 12% adrenal, in other manifestations of GA may not be noted at all). / S.I. Rogovskaya. “Androgen-dependent skin lesions and the possibilities of their correction in women (clinical lecture)”, Scientific Center for Obstetrics and Gynecology and Perinatology (Dir. - Acad. RAMS V.I. Kulakov) RAMS, Moscow // Consilium medicum-Gynecology - Volume 05 / No 1/2003 /www.media/gynecology/03_01/23.shtml/.

Diagnostic methods of immunological analysis are extremely important. Currently, immunological research methods allow not only to confirm or reject the immunological mechanisms of the pathogenesis of certain dermatoses, but, which is especially important, to reveal, for example, the features of localization of antigens in tissues, to establish the titer of antibodies in the blood directed against individual microstructures of the epidermis and dermis. Thus, the immunofluorescence method allows you to clarify the diagnosis in those complex cases when clinical and pathomorphological studies do not allow you to finally speak out in favor of a particular dermatosis. / Methods of immunological analysis in the diagnosis of skin diseases. www.kalitva.ru, December 18, 2007 /.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine pathology. The frequency of PCOS is about 30% of patients among patients of gynecologists-endocrinologists, and in the structure of endocrine infertility reaches 75%. The vast majority of researchers believe that PCOS is a heterogeneous pathology characterized by obesity, chronic anovulation, hyperandrogenism, impaired gonadotropic function of the ovaries, an increase in the size of the ovaries and the peculiarities of their morphofunctional structure. Many women with PCOS (50-80%) are obese. In recent years, numerous data have been obtained on the important role of leptin in the etiopathogenesis of this pathology. But in the bulk of the studies, the relationship between the level of leptin in total and free testosterone in women with PCOS against and without obesity was studied. Leptin is a protein hormone produced by fat cells (adipose tissue). The level of concentration of leptin in blood plasma is directly proportional to the total amount of fat in the body. Leptin acts on the hypothalamic receptors: it counteracts the effects of food intake stimulants (neuropeptide Y, anandamide) and promotes the effects of appetite-lowering substances (alpha-melanocytostimulating hormone (alpha-melanocytestimulating hormone, alpha-MSH). As a result, food intake is reduced. Thus, leptin is involved in the management of food intake. Leptin also stimulates the oxidation of fatty acids in the mitochondria of liver and skeletal muscle cells. This leads to a decrease in fat stores in the liver and muscle tissue. On adipose tissue, leptin like It has been shown that leptin can also be produced by osteoblasts (Iwamoto I., 2000; Reseland, J.E., 2001), stimulate bone mineralization and inhibit the formation of osteoclasts (Holloway, W.R., 2002), probably by increasing the secretion of osteoprotegerin.

In the available literature, we have not come across works that affect the relationship of the level of leptin in women with OHSS with the development of skin pathologies in them.

A detailed description of the method and examples of its clinical performance.

The inventive method is as follows. In women with PCOS at an early stage of the disease, a hormonal study is performed to predict the occurrence of acne and oily seborrhea of the face.

A hormonal examination is carried out on the 3-5th day of an independent or induced menstrual cycle. The concentration of LH, FSH, growth hormone (STH), testosterone (T), estradiol (E2), testosterone estradiol-binding globulin (TESG), 17-hydroxyprogesterone (17-OH), dehydroepiandrosterone sulfate (DEAS) in the blood serum is determined by radioimmun using test systems Immunotech (Czech Republic) or IHOKH (Belarus), the concentration of androstenedione (A), estrone (E1) and leptin - by the enzyme-linked immunosorbent assay using standard Diagnostics Biohem test systems. Canada Inc. (Canada) (G.E. Chernukha, V.L. Shevtsova, I.V. Blinova. "Comparative effectiveness of the use of insulin sensitizers in patients with polycystic ovary syndrome" // Journal "Difficult Patient", No. 1, 2007).

The performance of the proposed method is confirmed by the following clinical examples.

Example 1

Patient R-on L.I., medical history No. 301/32, 26 years. From the anamnesis: upon admission complained of menstrual irregularities with menarche type oligoamenorrhea, painful mensis, infertility I 8 years; mensis from 14 years after 28-30 days for 7 days, delays of up to 30 days, with pain, profuse; sexual life since 19 years; marriage I - 8 years, there were no pregnancies. Diagnosed with PCOS. On the scalp, hair of a mixed type, facial skin combined. Occasionally, single papular-pustular elements appear in the chin area before mensis.

The patient is prescribed a hormonal test and the enzyme immunoassay determines the level of leptin in the venous blood. According to the results of the analysis, the level of leptin was 12.7 ng / ml; those. an indicator exceeding 12.6 ng / ml, which allowed to predict the development of skin lesions in this patient. After 6 months at a follow-up, the following pathological changes were revealed on the skin: on the scalp, hair of mixed type, oily at the roots, the skin is hyperemic, covered with hemorrhagic crusts - seborrhea of the scalp; the skin on the face is oily, the pores are enlarged, severe acne (papular-pustular form). Thus, this clinical example confirms the possibility of making a prognosis of the development of skin pathology based on the study of the level of leptin in the blood.

Example 2

Patient Sh-ova N.A., 22 years old, medical history No. 1326/132. From the anamnesis: complaints about the absence of pregnancy for 1 year, delays of 1-2-3 months, mensis from 13 years old, were not established after 40-60-90 days for 10-30 days, without pain, profuse, from 1997 to 2000 passed courses of treatment at the gynecologist (biskurin, non-ovlon, marvelon for 3 months, Diana 35 - 1 year - without effect). Diagnosed with PCOS. On the scalp without pathology, on the face the skin is combined, the pores are enlarged.

The patient is prescribed a hormonal test and the enzyme immunoassay determines the level of leptin in the venous blood. According to the results of the analysis, the level of leptin was - 16.5 ng / ml; those. an indicator exceeding 12.6 ng / ml, which allowed to predict the development of skin lesions in this patient. At a follow-up appointment after 6 months, the following pathological changes were revealed on the skin: in the face area, the skin is combined, before the mensis spills up to 10 elements in the T-zone, acne is a papular-pustular form, secondary pigmentation is left behind. Thus, this clinical example confirms the possibility of making a prognosis of the development of skin pathology based on the study of the level of leptin in the blood.

Example 3

Patient C-eva E.S., 25 years old, medical history 7701/595. From the anamnesis: complaints of violation of mensis with menarche, delays of 4-5 months to 1 year, mensis from 16 years old, were not established, infertility for three years, was observed at the gynecologist for 9 years, received regididone. Diagnosed with PCOS. On the scalp without pathology, facial skin unchanged, sensitive.

The patient is prescribed a hormonal test and the enzyme immunoassay determines the level of leptin in the venous blood. According to the results of the analysis, the level of leptin was 12.6 ng / ml; those. an indicator not exceeding 12.6 ng / ml, which made it possible to predict the absence of skin lesions in this patient. At a repeated appointment after 6 months, pathological changes in the skin were not revealed: on the scalp without pathology, the skin on the face without changes, sensitive. Thus, this clinical example also confirms the possibility of making a prognosis of the development of skin pathology based on the study of the level of leptin in the blood.

The inventive method was examined 109 women with PCOS, in all patients (109 people) the level of leptin was determined; in 60 people, the leptin index exceeded 12.6 ng / ml, and these patients developed skin pathology.

Statistical analysis of the results of the study was carried out using the student coefficient. The differences between the variational series were considered significant at p less than 0.05.

In connection with cosmetic problems in women, against the background of skin manifestations in PCOS that contribute to the development of psychological changes, neurotic conditions, it seems especially relevant to forecast the development of pathological changes in the skin with PCOS, which will increase the effectiveness of early diagnosis and prevent the above problems.

This method allows predicting the development of skin pathology (the occurrence of acne and oily seborrhea) at an early stage of the disease, with the aim of taking preventive measures, and determining the strategy for the treatment of skin diseases in women with PCOS.

Claims (1)

A method for predicting the development of skin pathology in women with scleropolycystic ovary syndrome by hormonal examination of venous blood, characterized in that on the 3-5th day of an independent or induced menstrual cycle, the level of leptin in the venous blood is determined by an enzyme immunoassay and in the presence of an indicator exceeding 12.6 ng / ml, predict the development of acne and oily seborrhea of the face and head.