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International Medical Scientific Journal        Issue-3 

10.5281/zenodo.5713450 

77 

  



Art of Medicine           Volume-1 

International Medical Scientific Journal        Issue-3 

10.5281/zenodo.5713450 

78 

 

Art of Medicine International Medical Scientific journal 

 

Founder and Publisher Pascual Izquierdo-Egea 

Published science may 2021 year. Issued Quarterly. 

Internet address: http://artofmedicineimsj.us 

E-mail: info@artofmedicineimsj.us 

11931 Barlow Pl Philadelphia, PA 19116, USA +1 (929) 266-0862 

 

 
   

  



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Compleks pregravid preparation in the prevention of miscarriage in women 

with hyperandrogenism 

Sidikova Nigora Marifovna 

Tashkent Pediatric medical institute, Tashkent, Uzbekistan  

Sidikovanigora88@gmail.com 

 

Abstract: Hyperandrogenism is diagnosed in almost 10% of women 

worldwide and impairs the reproductive system: menstrual disorders are diagnosed in 

50-70% of patients, infertility in 60-80% of cases and miscarriage in 20-30% of 

cases. Comprehensive corrective pre-pregnancy treatment was used in these patients, 

and its efficacy was confirmed by the onset of pregnancy and normalization of the 

hormonal background. 

Keywords: hyperandrogenism, hormonal background, pregravidarial 

preparation. 

 

Miscarriage (MC) and infertility in women of fertile age is a very urgent 

medical and social problem. Hyperandrogenism (HA) is rightfully recognized as one 

of the causes of these conditions and a common risk factor for pathology of the 

reproductive system. GA is quite widespread in women of reproductive age. 

Violation of the secretion of androgens by the adrenal glands and ovaries, impaired 

metabolism of the hormones produced and leads to HA [4]. In almost ¾ women, HA 

causes disorders of menstrual and reproductive functions, which leads to infertility 

[1]. 

During pregnancy, women with HA often experience complications: the threat 

of termination of pregnancy, ischemic-cervical insufficiency (ICI), placental 

dysfunction, and the threat of premature birth. One or more of these complications 

cause miscarriage (FB) or premature birth [4]. 

Russian scientists cite some figures: SPB is noted in 20% of women, and in 

80% in the first trimester. Endocrine pathology, in particular HA, is the cause of 

habitual miscarriages in every fifth pregnant woman [2]. 

Pregnant women with GA have a proven high risk of perinatal complications; 

therefore, at the stage of pregnancy planning, pregravid preparation is mandatory in 

order to minimize the negative effects of an excess of androgens on pregnancy and 

reduce the incidence of complications [11]. 

HA in women also disrupts the reproductive system: menstrual irregularities 

(MC) are noted in 50-70% of patients, infertility - in 60-80%, NB - in 20-30%. 

Consequently, GA is not only a medical, but also a social problem, since against the 

background of internal and external changes occurring in a woman's body, the 

psychoemotional state changes and the quality of life decreases [9]. 

The most common pathology leading to HA in women is PCOS; it is diagnosed 

in three out of 4-5 women [5, 6, 7, 10]. Clinical symptoms of PCOS are well 

diagnosed: MC disorders, infertility, hirsutism. Pregnancy is possible only after 

mailto:Sidikovanigora88@gmail.com


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effective medical correction of the condition (treatment of infertility by stimulating 

ovulation) or surgical treatment [3]. 

Diagnosis of PCOS is based on the results of clinical, hormonal and ultrasound 

studies. The history should focus on oligomenorrhea with menarche, anovulation, 

primary infertility, early multiple SPD [3]. 

These facts involuntarily suggest that the attitude of the female population to 

such a formidable pathology as GA is not serious, which is most likely explained by 

the lack of knowledge of women about this pathology and the lack of active 

educational work at the level of primary health care, the media and the state as a 

whole. 

Correction and prevention of HA should be carried out starting with pregravid 

preparation and continued in early pregnancy. The duration of correction for each 

patient is individual and depends on the severity of the obstetric and gynecological 

history, the severity of clinical and biochemical symptoms of HA and concomitant 

somatic pathology. In women with infertility and / or with the usual SPD, correction 

implies the restoration of reproductive function and the preservation of the 

subsequent pregnancy with the minimization of androgen-dependent complications. 

Correction of GA and treatment of NECJ is extremely necessary both from the 

point of view of the health of each individual woman and the female population as a 

whole, and therefore the composition of the population and fertility in it. 

Objective: to develop and evaluate the effectiveness of diagnostic markers of 

complex corrective pregravid preparation in terms of the relationship between 

hormonal status and biochemical markers of the endometrium in women with 

hyperandrogenism. 

Material and research methods: 

We examined 146 women of reproductive age 21-35 years (the average age of 

the examined patients was 27.8 ± 2.89) with reproductive disorders (primary / 

secondary infertility, early SPD) against the background of clinical and / or 

biochemical symptoms of GA in history. Group I included 62 patients with PCOS 

with pre-obesity and degree I obesity (BMI within 25-34.9 points) aged 21 to 35 

years, the average age was 28.2 ± 1.34 years. Group II included 64 patients with 

PCOS and normal body weight (BMI in the range of 18.5-24.9 points) aged 23 to 35 

years, the average age was 29.8 ± 1.25 years. 

The control group (CG) included 20 pregnant women 22-34 years old without 

GA and with physiological hormone levels, with normal BMI, identical with the 

studied patients in terms of age and presence of extragenital pathology (mean age 

29.1 ± 1.16 years). 

We studied the prevailing nature of the distribution of subcutaneous fat (SFA) 

along the waist circumference (OT), with OT less than 80cm, the female (gynoid) 

type of SSS distribution was ascertained, and with OT over 80cm, the visceral 

(android) type. 

The severity of hirsutism was assessed according to the Ferriman-Gallwey 

scale [8], calculating the "hirsut number" in points, the norm was taken as a sum of 7-



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12 points, moderate hirsutism was stated with a hirsut number of 20-25 points, 

pronounced hirsutism - more than 25 points. 

Laboratory studies of the condition of the patients of all groups, including the 

control group, were carried out in parallel with the clinical examination for the first 

time upon treatment, then again 2 weeks after the completion of the course of pre-

gravid preparation. 

The laboratory examination consisted of standard and specific tests, based on 

the purpose and objectives of the study, its specificity and design: general clinical 

analysis of blood and urine, biochemical blood test, indicators of various links of 

hemostasis, levels of steroid hormones in serum and saliva, determination of 

infectious markers, which meant taking venous and peripheral blood and urine 

strictly on an empty stomach, excluding fatty and salty foods and spices the day 

before. 

The study of hormones in the blood serum and saliva in all patients of the main 

and CG implied the determination of gonadotropic hormones (LH, FSH), total 

testosterone, estradiol, progesterone, 17-ONP, DHEA-S, glycodelin (PP14) and 

IPFR-1. The results obtained for the patients of the main group were compared with 

the results for women in the CG. The hormonal background was studied in the first 

phase of MC, in dynamics after corrective therapy before pregnancy. 

The main groups of patients were divided by us according to the type of 

pregravid corrective therapy, each into 2 subgroups A and B. 

Pregravid preparation of patients A of subgroups I and II of groups consisted of 

standard conservative treatment, including biguanides (metformin 500 mg), 

stimulation of ovulation with agonists and antagonists of gonadotropin-releasing 

hormones, anti-estrogen drugs (clomiphene citrate) at 50-100 mg / day. under the 

control of ultrasound. We performed ultrasound to monitor the dynamics of follicle 

growth. Starting from the 14th day of the menstrual cycle, the patients took gestagens 

(dydrogesterone 10/20 mg or micronized progesterone 100 mg (daily dose - 200-300 

mg), continuing their intake with the onset of pregnancy. micronized progesterone 

was extended to 36 weeks to reduce the risk of complications at various gestational 

times. 

Pregravid preparation of patients in subgroups I and II of groups consisted of 

standard conservative treatment, adherence to a healthy lifestyle, exclusion from the 

diet of foods from fast-dissolving glucose and with a high index of insulin resistance. 

In order to increase the sensitization of cells to insulin, myoinositol 750 mg (daily 

dose up to 4000 mg) was included in the standard treatment. Stimulation of ovulation 

was carried out by agonists and antagonists of gonadotropin-releasing hormones, 

anti-estrogen drugs (clomiphene citrate) at 50-100 mg / day. under the control of 

ultrasound. With the onset of biochemical pregnancy, metformin was canceled, while 

myoinositol was continued. 

Results of our own research 

At the initial visit, all patients had complaints of primary or secondary 

infertility, MC, violations of MC disorders. When analyzing morphograms in 

pregnant women of groups I and II, an insignificant difference in body type was 



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noted. Most patients of group I were diagnosed with male type of hair growth, 

visceral type of obesity was diagnosed in 22.58% (n = 14) from puberty, in the 

remaining 77.42% (n = 48) - in the post-pubertal period (Table 1). In group II, the 

picture was similar - 81.25% (n = 52) had a female type of body structure. 

Table 1. Data of anamnesis and examination of patients of groups I and II and CG 

 

The diagnosis of PCOS was made taking into account the history, complaints 

and results of laboratory and instrumental research methods. We studied the 

hormonal background on days 2-3 with natural or induced MC - an increase in total 

testosterone up to 4.12 ± 0.26 ng / ml, DHEA-S - 9.83 ± 0.35 μmol / L, LH - 13.51 ± 

1.79 IU / L, FSH - 5.34 ± 0.55 IU / L, growth of 17-ONP no more than 1.85 ± 0.75 

ng / ml, LH / FSH ratio - 2.78 ± 0.75, those. exceeding more than 2, which is a 

diagnostic criterion for PCOS, was typical for all women in the main groups. 

Signs of PCOS by ultrasound on the 3-7th day of the MC (an increase in the 

volume of the ovaries by more than 10 cm3 due to a hyperechoic stroma with many 

(more than 10-12) diffusely and / or along the periphery in the form of a necklace of 

follicles, up to 8-10 mm in size, compaction ovarian capsules) were found in the 

majority of women in the main groups. Visualization of such a picture is typical for 

women with GA. 

The hormonal background in GA differs sharply from the CG indicators, so all 

indicators differ significantly (p <0.05), with the exception of FSH and 17-SNP, the 

differences of which are not statistically significant (p≥0.05), which, apparently, 

associated with the nature of the GA - SKPJ. Also, some vitamin D deficiency was 

noted in patients of the main groups. 

The levels of thyroid-stimulating hormone in the patients of the main groups 

were almost twice as high as those in the CG, and the indicators of prolactin were one 

and a half times higher than those in the CG in the blood serum and in saliva, and the 

indicators of the I group were significantly higher than the levels of the II group of 

patients (p <0.05). 

We stated that there was no difference in the LH / FSH ratios in all groups 

between the studies in blood serum and in saliva, which proves the consistency of the 

Options I group (n=62) II group (n=64) CG (n=20) 

Primary infertility 44 (70,97%) 14 (21,88%) -- 

Secondary infertility 14 (22,58%) 47 (73,44%) -- 

Early pregnancy loss 26 (41,94%) 17 (26,56%) -- 

MC violations 52 (83,87%) 46 (71,88%) -- 

Male body type 60 (96,77%) 52 (81,25%) -- 

Female body type 2 (3,23%) 12 (18,75%) 20 (100%) 

Hirsutism scores 22,7±1,5  22,2±1,6 4,7±0,68 

Acne 10 (16,13%) 9 (14,06%) -- 

Striae 38 (61,29%) 26 (40,63%) -- 

Acanthosis nigroid 14 (22,58%) 8 (12,50%) -- 



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study of the hormonal background of patients with HA and PCOS in terms of 

concentration in saliva. 

Analysis of statistical processing revealed the presence of a significant (p 

<0.05) average strength of the correlation between BMI and IPFR-1, in group I 

patients (r = 0.48), with glycodelin (r = 0.47), androstenedione (r = 0.50), free 

testosterone (r = 0.42), hirsutism scores (r = 0.44). We stated that there was no 

correlation between the above parameters in the control group of patients (r <0.23). 

We found strong direct correlations between BMI and the level of 

dihydrotestosterone (r = 0.60) and glycodelin PP14 (r = 0.58). 

In patients with GA, a significant (p <0.05) direct relationship was found 

between the scores of hirsutism and the levels of the following hormones: 

androstenedione (r = 0.51), free testosterone (r = 0.47), glycodelin (r = 0.48 ), IPFR-1 

(r = 0.46). A significant (p <0.05) average strength direct relationship was found 

between the level of glycodelin and the levels of IPFR-1 (r = 0.40), androstenedione 

(r = 0.41), free testosterone (r = 0.44). 

The indicators of the hormonal background of the patients of the main and 

control groups when measured in saliva were displayed more accurately and had 

many correlations identical to the blood indicators within the measurement, but at the 

same time, the levels of free testosterone and DHEA-S in saliva were significantly 

higher in the patients of the main groups, it should also be taken into account that the 

collection of saliva and its study is much easier, therefore, the main hormones were 

measured by us by the level of their concentration in saliva.  



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Table 2. Hormonal background of patients of groups I and II and CG before corrective therapy 

Note:* – statistically significant intergroup differences I and II relative to the control group (p<0,05). 
   

Options 
Group I (n = 62) Group II (n = 64) KG (n = 20) 

In blood In the saliva In blood In the saliva In blood In the saliva 

Thyroid stimulating hormone, μIU / ml 3,4±0,35* 3,2±0,32* 3,3±0,34* 3,2±0,31* 1,9±0,28 1,5±0,27* 

Prolactin, μIU / ml 
612,3±22,4* 594,9±22,9* 439,8±23,4* 499,3±22,1* 

413,7±24,

2 
337,6±22,5 

Total testosterone, ng / ml 2,17±0,15* 1,65±0,12* 2,01±0,16 1,89±0,13* 2,71±0,15 1,51±0,13 

Total testosterone, ng / ml 4,32±0,37* 4,09±0,35* 4,12±0,36* 3,75±0,28* 3,87±0,09 3,27±0,10 

Free testosterone, pg / ml 4,79±0,13* 4,4±0,15* 3,98±0,15* 3,75±0,16* 1,2±0,15 0,8±0,10 

Dihydrotestosterone, pg / ml 
450,3±12,4* 415,6±12,3* 395,2±16,3* 327,3±12,4* 

191,9±11,

4 
116,7±10,3 

Androstenedione, nmol / l 13,5±3,9* 13,1±3,4* 11,7±3,25* 11,5±3,3* 0,89±0,25 0,90±0,20 

Dihydroepiandrosterone sulfate, μmol / l 13,55±0,55* 12,09±0,60* 10,82±0,63* 10,11±0,60* 6,8±0,16 5,04±0,13 

17-hydroxyprogesterone, ng / ml 1,85±0,75 1,79±0,80 1,49±0,68 1,45±0,60 1,02±0,20 0,97±0,18 

LH, IU / l 13,51±1,79* 12,47±1,89* 11,8±1,4* 10,09±1,25* 8,5±0,95 7,8±0,86 

FSH, IU / l 5,9±0,50 5,6±0,35 5,34±0,45 5,01±0,25 5,5±0,15 5,3±0,19 

LH / FSH 2,28±0,75* 2,28±0,65* 2,19±0,28* 2,02±0,55* 1,56±0,22 1,52±0,35 

Glycodelin PP14, μg / ml 
14,81±0,91* -- 18,72±0,85* -- 

33,58±1,3

5 
-- 

IPFR-1, ng / ml 
537,08±35,6* -- 496,23±36,2* -- 

367,5±26,

8 
-- 

25-OH D3 
22,63±1,65  29,57±1,79  

31,89±1,8

7 
 



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During the treatment, pregnancy occurred in 88.89% (n = 56) patients: 26 

(83.87%) from group Ib and 30 (93.75%) from group IIb. Of all our patients who 

became pregnant, 39.42% (n = 41) became pregnant during the first 2 months, and 

60.58% (n = 63) during the 3rd - 4th months of corrective pregravid preparation. In 

the control group, this ratio was 60% (n = 12) to 40% (n = 8), respectively. There 

was no statistically significant difference in the timing of pregnancy between the 

subgroups, despite the difference in BMI and corrective pregravid preparation. 

After the completion of the complex corrective pregravid preparation of the 

patients of both groups, the level of almost all hormones in the study groups was 

comparable, however, within each group, the levels of hormones significantly 

differed between the subgroups. 

In Ia and IIa subgroups, the levels of hormones in the blood serum and saliva 

differ more from the norm than the indices of the Ic and IIc subgroups. There were 

statistically significant differences in the levels of total and free testosterone, 

dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate and 

glycodelin (p <0.05). 

Attention should be paid to statistically significant differences between the 

two subgroups of corrective pregravid training, which indicates a clear higher 

efficiency of the complex training offered by us, which also has a good effect on 

patients in subgroup I of group with preobesity and obesity of I degree (p <0.05) , 

but the expected best efficacy was obtained by us in subgroup II of group of 

patients with normal body weight. 

It should be noted that the level of vitamin D in the blood serum of patients 

has normalized, and we have achieved greater success in this aspect in the 

subgroups of the main groups, the difference is significant (p <0.05). 

The levels of thyroid-stimulating hormone and prolactin by the end of 

pregravid preparation were slightly lower in the B groups of both main groups. The 

LH / FSH ratio in all subgroups in serum and saliva was identical, which again 

confirms the possibility of monitoring the effectiveness of therapy by the 

concentration of hormones in saliva. 

 
 



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Table 3. Hormonal background of patients of the main groups and CG after corrective pregravid therapy 

Note: * – statistically significant differences between A and B subgroups of both groups (p<0,05).  
 

Options 
I A group (n=31) I B group (n=31) II A group (n=32) II B group (n=32) 

In blood In the saliva In blood In the saliva In blood In the saliva In blood In the saliva 

Thyroid stimulating hormone, 

μIU / ml 
2,5±0,35 1,6±0,30 2,1±0,34 1,4±0,29 2,4±0,32 1,6±0,29 2,2±0,31 1,7±0,28 

Prolactin, μIU / ml 291,1±32,4 196,8±28,4 270,6±32,8 204,8±29,2 296,3±30,4 201,9±25,5 259,6±27,8 198,3±20,8 

Total testosterone, ng / ml 2,78±0,15* 2,46±0,12* 2,45±0,15* 2,09±0,10* 2,21±0,17 2,08±0,14 1,88±0,08 1,64±0,07 

Free testosterone, pg / ml 2,41±0,18* 2,15±0,14* 1,73±0,16* 1,62±0,14* 1,55±0,15 1,34±0,13 0,97±0,10 0,81±0,09 

Dihydrotestosterone, pg / ml 252,1±13,6* 224,9±12,5* 223,6±13,4* 209,4±12,9 224,7±11,8 210,1±11,5 197,6±10,4 170,9±10,1 

Androstenedione, nmol / l 10,04±3,9* 9,07±3,8* 8,27±3,7* 7,09±3,4* 9,4±3,35 7,13±3,25 7,44±3,15 6,81±2,95 

Dihydroepiandrosterone 

sulfate, μmol / l 
9,37±1,85* 8,14±1,82* 6,02±1,78* 5,78±1,73* 6,13±1,63 5,04±1,58 4,31±1,23 4,04±1,18 

17-hydroxyprogesterone, ng / 

ml 
1,23±0,84 1,13±0,80 1,08±0,82 0,94±0,56 1,11±0,60 0,96±0,45 0,95±0,35 0,84±0,30 

LH, IU / l 8,93±1,25 8,18±1,22 7,87±1,15 7,66±1,12 7,61±1,13 7,54±1,11 6,73±1,08 6,33±1,05 

FSH, IU / l 5,39±0,55 5,21±0,41 5,36±0,38 5,07±0,35 5,76±0,32 5,43±0,29 5,58±0,34 5,31±0,25 

LH / FSH 1,58±0,31 1,57±0,21 1,47±0,28 1,51±0,21 1,32±0,22 1,38±0,22 1,21±0,30 1,19±0,31 

Glycodelin PP14, μg / ml 25,31±0,82*  31,74±0,84  27,67±0,80*  33,51±0,56  

IPFR-1, ng / ml 413,98±36,2  376,31±35,4  387,63±34,5  365,8±27,9  

25-OH D3 42,7±2,75*  51,37±2,86  43,56±2,71*  54,87±2,65  



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Attention should be paid to statistically significant differences between the two 

subgroups of corrective pregravid training, which indicates a clear higher efficiency 

of the complex training offered by us, which also has a good effect on patients in 

subgroup I of group with preobesity and obesity of I degree (p <0.05) , but the 

expected best efficacy was obtained by us in subgroup II of group of patients with 

normal body weight. 

 

Conclusion 

For the most part, it is advisable to measure hormonal levels by studying the 

saliva of patients, given the presence of strong correlations between the levels of 

hormones in serum and saliva. 

The study of free testosterone, DHA-C glycodelin and IPFR-1 already at the 

stages of pregravid preparation as a marker of the processes occurring in the body of 

women, especially in the presence of PCOS and HA, is of great diagnostic value. 

The proposed and tested by us complex corrective pregravid training of 

patients with HA and PCOS with normal body weight, as well as with preobesity and 

obesity of the 1st degree, showed greater efficiency, manifested in a greater 

proportion of pregnant patients relative to standard pregravid training. 

 

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