The impact of the war in Ukraine on the physical and sexual development of girls with menstrual disorders

The health of the younger generation is a public value. Today, the state of health of teenage girls is of particular concern due to its progressive deterioration. Purpose - to study the features of the clinical course of menstrual function disorders in adolescent girls with comorbid mental health disorders. Materials and methods. 154 girls aged 11-17 were examined with menstrual cycle disorders (77 with oligomenorrhea (OM) and 77 with abnormal uterine bleeding (AUB)). Assessment of physical and sexual development, age of menarche was carried out. Depending on the examination by a psychiatrist, all girls with OM and AUB were divided into groups: without deviations in mental status, with anxiety-phobic disorders and depressive states. Results. It was found that the average growth indicators were probably higher in girls with OM in relation to adolescents with AUB, especially in the presence of psychopathology. The use of BMI did not reveal a significant difference when comparing patients with OM and AUB. Abnormalities of sexual development were probably more often registered in patients with AUB, with its advance, this acquired a significant difference (p˂0.01) and depended on both body mass index (BMI) and psychopathology. If the percentage of patients with disorders of sexual development did not differ depending on psychopathology in girls with AUB, then in adolescents with OM, the specific weight of girls with abnormalities of sexual development increased with the appearance of psychopathology. The average age of menarche was significantly lower in patients with AUB compared to patients with OM (p˂0.003). Early menarche was more typical for AUB. Much more often in adolescents with AUB, it was registered with normative fluctuations of BMI and its excess, as well as with anxiety-phobic disorders both with AUB and OM. Conclusions. The analysis of the conducted studies indicates reliable differences regarding the clinical course of menstrual function disorders by the type of OM and AUB with comorbid psychopathology. It was established that there are significant differences in such indicators as growth, puberty, time of menarche, which depended on the type of menstrual disorders and comorbid psychopathology. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors.

Readers will immediately notice that what most of us recognize as "Tanner Staging" has been replaced by the term "Sexual Maturity Rating." A quick review of recent literature will show that "Sexual Maturity Rating" is becoming the more accepted term.Puberty is a time of rapid linear growth and multiple physical changes. Accurately identifying the onset of puberty and how this relates to height velocity is essential to recognizing normal and abnormal growth patterns. The onset of puberty is also a critical time for the identification and treatment of individuals with persistent gender dysphoria.After completing this article, the reader should be able to:Puberty is broadly defined as the time at which a child develops secondary sexual characteristics and reproductive function. Puberty results from a complex sequence of biological events mediated by genetic, hormonal, and environmental factors that are characterized by the maturation of gametogenesis and secretion of gonadal hormones. Adolescence is a term often used interchangeably with puberty and is a stage that encompasses puberty as well as cognitive, psychological, and social changes.Gonadarche refers to sex hormone production from the ovary or testis and is triggered by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary. Adrenarche represents the increase in adrenal androgen production that leads to the development of pubic hair (pubarche), axillary hair, sebaceous gland (acne), and apocrine gland (sweating, body odor). Thelarche is the onset of breast development with the development of breast buds. Menarche is the onset of menstrual cycles in females.Pubertal development requires activation of the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus secretes pulsatile gonadotropin-releasing hormone (GnRH), which signals the gonadotroph cells in the anterior pituitary to release the gonadotropins LH and FSH. In general, LH primarily stimulates specialized interstitial cells (theca cells in the ovary or Leydig cells in the testes) to produce androgen, while FSH primarily stimulates the ovarian follicle or seminiferous tubules to produce estradiol, inhibin, and gametes (egg or sperm). Interstitial and follicular/tubular compartments also act through paracrine mechanisms (communication of cell to surrounding cells) to form estradiol and regulate sex steroid and gamete development.In girls, FSH promotes the growth of ovarian follicles and, together with LH, signals the ovary to make estradiol. Estradiol production results in breast development and growth of the skeleton. As estradiol promotes maturation of the skeleton, eventually estradiol also leads to fusion of the growth plates and cessation of growth. At the time of menarche, estradiol prepares the endometrium of the uterus for implantation.In boys, LH stimulates the Leydig cells of the testes to produce testosterone that, in turn, promotes growth of the seminiferous tubules, resulting in an increase in testicular volume. Testosterone production due to FSH also induces growth of the penis, deepening of the voice, growth of hair, and increased muscularity.Sex steroids provide negative feedback on GnRH and gonadotropin production. Inhibin is a hormone secreted by the gonads that also provides negative feedback by decreasing FSH production. Later in development, ovulation in girls results from maintenance of a high estradiol concentration for a critical amount of time; this estradiol concentration provides positive feedback, which causes the LH surge that results in ovulation.Pediatric assays should be used when assessing gonadotropin and sex hormone concentrations in children, as may be necessary in the evaluation of ambiguous genitalia or precocious puberty. LH and FSH concentrations are high during the first 3 postnatal months. LH decreases to almost undetectable values by the age of 6 months in boys and girls. FSH concentrations also decrease after 6 months but can remain elevated in girls until age 3 to 4 years. The HPG axis then remains quiescent until puberty.LH values vary widely during childhood, ranging from 0.06 to 4.77 mIU/mL (0.06–4.77 IU/L) in boys and 0.1 to 14.7 mIU/mL (0.1–14.7 IU/L) in girls. Generally, LH is the most useful gonadotropin to assess for the onset of puberty. An LH value of greater than 0.3 mIU/mL (0.3 IU/L) is consistent with the onset of central puberty. However, an undetectable basal LH value alone has low sensitivity for central puberty. Pubertal FSH concentrations range from 0.21 to 8.74 mIU/mL (0.21–8.74 IU/L) in boys and 0.64 to 10.98 mIU/mL (0.64–10.98 IU/L) in girls. Importantly, FSH concentrations have been noted to be elevated in premature thelarche, a normal variant consisting of breast development not associated with central precocious puberty. An elevated FSH value, therefore, is not a reliable measure of the onset of central puberty.Estradiol is the primary circulating estrogen in girls, and ultrasensitive assays using liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology are most useful when measuring concentrations in prepubertal girls. Estradiol values are generally equal to or less than 16 pg/mL (58.7 pmol/L) in prepubertal girls. By age 10 to 11 years, estradiol values are equal to or less than 65 pg/mL (238.6 pmol/L), by age 12 to 14 years are equal to or less than 142 pg/mL (521.3 pmol/L), and by age 15 to 17 years are equal to or less than 283 pg/mL (1038.9 pmol/L). Estradiol concentrations in boys are usually less than 31 pg/mL (113.8 pmol/L).Testosterone levels by LC/MS/MS in prepubertal girls are equal to or less than 8 ng/dL (0.3 nmol/L) and remain less than 33 ng/dL (1.2 nmol/L) by Sexual Maturity Rating (SMR) 5. Testosterone levels in boys at SMR 1 are generally less than 5 ng/dL (0.2 nmol/L), less than 167 ng/dL (5.8 nmol/L) at SMR 2, between 21 and 719 ng/dL (0.7–25 nmol/L) at SMR 3, 25 to 912 ng/dL (0.9–31.7 nmol/L) at SMR 4, and 110 to 975 ng/dL (3.8–33.8 nmol/L) at SMR 5.Pulsatile GnRH release and consequent pulsatile LH and FSH secretion occurs before most physical signs of puberty. In early puberty, this pulsatile release takes place mostly at night, but as puberty progresses, gonadotropin release develops into the established adult pulsatile pattern throughout the day. This "pulse generator" appears to be fully intact at birth and is likely inhibited by unknown factors during childhood.The initiation of pulsatile GnRH release is not completely understood, although indirect upstream signaling pathways have been found to regulate GnRH-secreting neurons, such as kisspeptin, leptin, and gonadal steroids. Kisspeptins are peptide products of the KiSS-1 gene and are the natural ligands for the G protein-coupled receptor GPR54, which is found on GnRH neurons. Kisspeptins stimulate GnRH neurons to secrete GnRH. Interestingly, kisspeptin receptor and ligand have also been found within the brainstem, spinal cord, pituitary, ovary, prostate, and placenta, suggesting regulation of the reproductive axis on multiple levels. The role of kisspeptins as stimulators of GnRH secretion became apparent when mutations in the kisspeptin receptor were found to be associated with idiopathic hypogonadotropic hypogonadism, while activating mutations have been associated with precocious puberty. Kisspeptin is a target for steroid hormones and may explain how sex steroids exert positive and negative feedback on GnRH secretion. (1)Leptin is a peptide produced by adipose tissue that circulates in proportion to energy stores. It provides negative feedback in the hypothalamus to control appetite and energy use. Although leptin does not have a direct role in puberty induction, studies have demonstrated that leptin targets the KiSS1 neurons and likely influences GnRH secretion. (1)Although puberty often occurs in a predictable pattern, the age of onset, sequence, and tempo may vary. SMR staging of sexual development or Tanner staging provides a consistent method of monitoring a child's progression through puberty. Separate scales are used for gonadarche (breasts in females and testicular size in males) and pubic hair (Table 1).Accurate staging for breast and testicular development requires palpation. Breast tissue cannot be distinguished from adipose tissue by inspection, and inspection alone can lead to inaccurate pubertal staging. Palpation of a subareolar breast bud indicates the onset of puberty in girls. Direct measurement of testicular size by palpation is preferable to visual estimation. A testicular volume of 3.0 mL or a length of equal to or greater than 2.5 cm indicates SMR 2 gonadarche. Pubic hair development may result from gonadal or adrenal androgen production. In some cases, distinguishing increased body hair from early sexual hair growth can be difficult. Generally, pubic hair is coarse and curly, while body hair is fine and straight.Girls normally begin puberty between 8 and 13 years of age. (2) The initial physical sign of puberty is most often thelarche. Ovarian enlargement and growth acceleration are present at the onset of breast development but may not be obvious at initial presentation. Thelarche is typically followed by pubarche, although 15% of girls have pubarche as the first sign of puberty. Recently, Biro et al (3) examined hormonal changes in peripubertal girls and found dehydroepiandrosterone sulfate (DHEA-S) concentrations increased 24 months before breast development, while estradiol and testosterone increased between 6 and 12 months before breast development. In a separate study, the same research group also found the onset of breast development to occur at 8.8, 9.3, 9.7, and 9.7 years for African American (AA), Hispanic, white non-Hispanic (NHW), and Asian participants, respectively. (4) Breast development may occur up to 1 year earlier in AA and Mexican American girls and can be normal in the 7th year in these specific populations.Breast development may be asymmetric and can be associated with breast tenderness. Although asymmetry of the breasts is common between SMR 2 and 4, other causes of asymmetry include juvenile fibroadenoma or abscess. Sixty-eight percent of breast masses in adolescents are due to fibroadenomas, which are more common in AA girls. Fibroadenomas are not associated with malignancies and are usually 2 to 3 cm, although giant fibroadenomas are greater than 5 cm. The peak incidence occurs in late adolescence. Less common causes of breast masses in adolescent girls include duct obstruction, retroareolar cysts, phyllodes tumors, intraductal papilloma, juvenile papillomatosis, breast contusion, and cancer. Breast cancer is extremely rare in girls younger than age 14 years. The cause of an adolescent breast mass can often be determined by history and serial physical examinations. Imaging may be helpful in some cases, most often ultrasonography, and if indicated, biopsy. (5)Gonadarche and adrenarche are frequently temporally related but are distinct processes. Although corticotropin production is required for adrenarche, the trigger for adrenarche is not fully understood. The typical sequence of pubertal events is shown in Figure 1. Rosenfield et al (6), using data from National Health and Nutrition Examination Survey (NHANES)-3, found the mean onset of SMR 3 pubic hair in nonobese girls to be 11.57 years, 11.6 years in NHW, 10.65 years in non-Hispanic black, and 11.63 years in Mexican American girls. This compared to an earlier mean onset of SMR 3 pubic hair of 11.39 years in obese girls.Menarche refers to the first menstrual bleed and usually occurs 2 to 2.5 years after the onset of puberty. Physiologic leukorrhea due to estradiol stimulation of the vaginal mucosa typically begins 6 to 12 months before menarche and results in a thin, white vaginal discharge with no odor. Initially, menarche is often not associated with ovulation. The timing of menarche has not been shown to be advancing as quickly as other pubertal changes, with the average age of menarche between 12 and 12.5 years, similar to that reported in the 1970s. Examining the NHANES-3 database, the Rosenfield group found the mean age of menarche in obese girls was 12.06 years compared to 12.57 in nonobese girls. (6)Boys typically begin puberty between ages 9 and 14 years. The onset of male puberty is marked by testicular enlargement, and usually within 6 months, penile length increases and pubic hair develops. Testicular enlargement at the onset of puberty is described as a volume greater than 3 mL or testicular length equal to or greater than 2.5 cm. Pubarche follows, with the development of pubic hair and other secondary sexual characteristics, including axillary hair, body odor, and sometimes acne. Within 1 to 1.5 years of starting puberty, boys have often reached SMR 3 for pubic hair. Linear growth begins to accelerate during genital and pubic hair SMR 2, and the pubertal growth spurt and spermarche typically occur between SMR 3 and 4 or around a testicular volume of 10 to 12 mL (Fig. 1). (7) Spermarche is the term used for the time of the first sperm production and is due to the production of testosterone. Further masculinization, with facial hair appearing and voice deepening, typically occurs in the fourth stage of puberty. Although adrenarche and gonadarche frequently overlap, adrenarche can sometimes precede gonadarche by 1 to 2 years in boys.At the onset of puberty, there can be asymmetric testicular development and gynecomastia. Pubertal gynecomastia occurs in approximately 50% of boys, usually in pubic hair SMR 3 to 4, and typically resolves within 2 years. Gynecomastia that persists or prepubertal breast development in a boy should prompt further evaluation for estrogen excess, androgen deficiency, or liver dysfunction.Historically, the mean onset of puberty in boys was reported to be around 11.64 (SD 1.07) years, with 95% of boys experiencing the onset of genital development between 9.5 and 13.5 years. (8)(9) More recently, the actual onset of male puberty has been shown to be earlier than it was 40 years ago, and there are differences by ethnicity. Data from the Pediatric Research in Office Settings (PROS) Network published in 2012 showed that the mean age of pubertal onset in boys was 6 months to 2 years earlier than in past studies, with mean age of onset of SMR 2 gonadarche for NHW, AA, and Hispanic boys of 10.14, 9.14, and 10.04 years, respectively, and for SMR 2 pubic hair of 11.47, 10.25, and 11.43 years, respectively. (10) PROS data concluded that overall, AA boys start puberty earlier, but the transition to SMR 5 puberty at age 15 years was similar for all boys, regardless of ethnicity.The testicular self-examination should be initiated during the pubertal years. Such examination can help identify any testicular abnormalities, particularly testicular masses. Testicular cancer is the most common malignancy in men ages 20 to 35 years, and routine self-examination has been shown to help with early diagnosis and treatment that improves outcomes.Growth velocity is important to monitor in all children, especially during puberty, because normal and abnormal variants of pubertal maturation may come to medical attention due to departure from the child's established growth pattern. Further, systemic illnesses may first present with poor growth before the onset of other symptoms, as is often the case in inflammatory bowel disease (IBD) or celiac disease. Of note, girls have their growth spurt earlier, typically between SMR 2 and 3, while boys have their growth spurt between SMR 3 and 4 (Fig. 1). (11) The pubertal growth spurt occurs over 2 to 3 years, with peak height velocity (HV) in boys ranging from 5 to 11 cm/year and in girls from 6 to 10 cm/year.Kelly et al (12) recently published age-based reference ranges for annual HV (Figs 2 and 3). They found that although the age of pubertal onset is decreasing, the relationship of growth velocity to SMR remains consistent. Interestingly, they found that AA girls started puberty earlier and had a greater HV between 8.5 and 10.4 years but had slower HV after age 11.5 years. AA boys had greater HV at age 12 years than non-AA boys. Growth and puberty are 99% complete by the time the bone age reaches 17 years.Delayed puberty is defined as lack of signs of pubertal development at an age 2 to 2.5 SDs above the mean for the population or about 13 years for girls and 14 years for boys. Delayed puberty can be divided into primary and secondary hypogonadism based on circulating concentrations of LH and FSH. Primary hypogonadism is associated with high serum concentrations of LH and FSH, while secondary hypogonadism is associated with low or normal LH and FSH values and can be functional, anatomic, or congenital. Table 2 lists causes of delayed puberty.Evaluation of delayed puberty involves a careful history and physical examination that includes height, weight, and pubertal staging over time. A thorough history should address nutritional habits, exercise intensity, prior illness, and medications because these can influence the age of onset of puberty. The presence of a midline defect is associated with a higher incidence of GnRH deficiency and may suggest hypogonadotropic hypogonadism. Similarly, neurologic symptoms such as headache, visual disturbances, and anosmia may suggest a central nervous system (CNS) disorder. Extracting a positive family history of constitutional delay of puberty (CDG) or congenital GnRH deficiency is very helpful.One important step is to determine if pubertal development is totally absent or began and then stopped. Observation of the growth pattern can guide diagnosis. For example, patients with CDG show delayed growth, adrenarche, and sexual development along with declining growth velocity and delayed bone age (radiograph of the left hand and wrist). Standing height and weight should be plotted on an appropriate curve and HV should be plotted as well. Arm span can be helpful; an arm span longer than the height by 5 cm suggests delayed epiphyseal closure due to hypogonadism. Testicular size should be measured and the testicles examined for asymmetry because gonadal tumors can occur in several disorders of sex differentiation.Laboratory testing in delayed puberty should start with assessment of LH, FSH, and estradiol in girls and testosterone in boys. By adolescence, those with primary hypogonadism have elevated LH and FSH values. Patients found to have primary hypogonadism should have a karyotype or comparative genomic hybridization array obtained to evaluate for Klinefelter syndrome in boys (genetic defect due to an extra X chromosome) or Turner syndrome in girls (45XO or mosaic). Additional testing for Fragile X permutation (55-200 CGG repeats in the Fragile X gene [FMRI]) should be considered in girls with primary ovarian insufficiency.Baseline concentrations of LH and FSH are typically low in both CDG and secondary hypogonadism. No single diagnostic test can distinguish CDG from hypogonadotropic hypogonadism other than observation for spontaneous pubertal development by age 16 to 18 years. However, general laboratory testing for delayed or stalled puberty may include by such as celiac and function. GnRH stimulation testing cannot between patients and those with CDG because of the between LH and FSH should be measured because can present with puberty. can cause delayed puberty. should include both a and because a value with low suggest central due to may be such as because patients with GnRH deficiency are more likely to have normal adrenal maturation in to those with although androgen values in the studies used in the evaluation of delayed or stalled puberty include a bone age which of for growth and maturation as well as of adult bone ages can provide about adult height Patients with CDG have bone ages of 12 to 13 years that not Delayed or puberty may also present in girls with of which can be primary menarche by age 15 or secondary of for more than 6 months in girls were may be helpful in girls with delayed puberty to determine the presence of a The uterus is absent with androgen and disorders of duct development. Testicular should be if a testicular mass is is if there is for central hormone or and in the presence of neurologic symptoms suggesting a central most common diagnosis associated with delayed puberty is constitutional delay of puberty but this is a diagnosis of A of and laboratory data from adolescents to an for delayed puberty found that CDG was the diagnosis in of and of Delayed but spontaneous pubertal development due to hypogonadotropic hypogonadism in and the causes growth hormone deficiency, poor weight systemic disorders such as juvenile idiopathic and hypogonadism was found in and was often due to most or percent of were Interestingly, to 15% of GnRH deficiency due to syndrome spontaneous after treatment with sex earlier puberty has been by recent studies in both the and associated with earlier puberty include growth and is important not to common of normal puberty for precocious puberty, most premature and premature adrenarche have often present in the years with breast development but no growth Breast tissue typically resolves with no other development of secondary sexual is a result of elevated adrenal are typically than for target height and usually have bone age of approximately 2 In values are elevated but with pubic hair is defined as an that with the or of natural hormones and includes some and a with estrogen and are found in including and are other that have been found to have have for further research into and a with the recent earlier for age or with or SDs are more likely to have precocious pubarche, an earlier onset of pubertal development and menarche, and progression of puberty than appropriate for age generally start puberty at a normal time but earlier than their peak HV is reached at a younger age and is than for those have earlier which may for adult other than in those are that may to their pubertal growth pattern include rapid weight in early childhood, and increased growth has a influence on pubertal development and can explain as as of the in pubertal and are associated with earlier puberty, while is associated with pubertal are obese show increased of growth starting in early in obese individuals is typically associated with bone age usually show a peak HV and have been shown to have a growth in height throughout the years. The height of obese has been shown to equal that of nonobese as is well established that promotes the onset of puberty in girls, but the data on and male puberty have been literature that the onset of male puberty, but more recent data suggest that the onset of male puberty by about years. In a recent of more than boys, et al found earlier enlargement of the testicular volume in and obese boys and earlier pubertal maturation compared to and A increase in concentrations occurs during the time when show the increase in body mass which may that body influences the activation of adrenal androgen the timing of pubertal development in and is associated with delayed onset of puberty, pubertal growth and age of can be a result of increased energy from disorders such as celiac and growth and height has been reported in with disorders during adolescence, with growth on length of the illness, the of and when was and pubertal delay are associated with Growth to be a more than delayed puberty and is more common in disease than studies showed in the onset of puberty and menarche in patients with and of about 1.5 years in girls and years for boys. However, these studies were at a time when there was on for and more recent studies more but age at As with factors such as age at diagnosis and to treatment an important pubertal growth and in with have been reported that are more in boys than girls. However, data from et al found that adult were not from the general a history of growth in those had suggesting that may height in have onset of puberty can be a time for individuals with gender is a diagnosis and of to individuals with persistent identification and with the gender role of their and childhood, as a specific gender develops and is further by with and the that of the to sex steroids influences gender but there are this is not the In approximately to of cases, does not into or it is important that all and adolescents with be and by a with in child and adolescent and that no social gender or hormonal treatment be in prepubertal diagnosis of should be based on a complete evaluation that is by the involves early pubertal with GnRH by SMR 2 to 3 of puberty. Pubertal is followed by initiation of sex steroid treatment to the gender at age 16 years and the of the is 18 years pubertal is because it the physical progression of puberty, which often causes on the to a pubertal has also been associated with and physical are to the GnRH and the is if the child or

The aim of the study was to determine the relationship between disorders of menstrual function in adolescence and the risk of nonalcoholic fatty liver disease (NAFLD) with comorbid gastrointestinal pathology. Materials and methods. We examined 129 adolescent girls aged 12–17 years with menstrual disorders (61 with abnormal uterine bleeding (AUB) and 68 with oligomenorrhea (OM)) and measured anthropometrics, indices of lipid and carbohydrate metabolism and liver enzymes. Data are presented in the form of mean (M), standard deviation (SD) and median (Me), a factorial model was developed. Results. The study shows the peculiarities of the clinical course of menstrual function disorders in girls of puberty age. Patients with AUB were characterized by significantly lower average body mass indices, they were younger compared to patients with OM. The nature of metabolic changes that depended on the type of menstrual disorders in teenage girls was clarified. Adolescents with AUB had statistically significantly higher average levels of immunoreactive insulin, HOMA index, triglycerides, very low-density lipoprotein cholesterol, aspartate aminotransferase. This creates conditions for the formation of nonalcoholic fatty liver disease. A model was created regarding the participation of dyslipoproteinemia, changes in the carbohydrate spectrum and levels of liver enzymes in the formation of nonalcoholic fatty liver disease in girls with menstrual cycle disorders. Conclusions. Disorders of menstrual function are associated with an increased risk of NAFLD formation. Adolescent girls with menstrual disorders need metabolic screening. The atherogenic profile of lipoproteinemia, marked changes in the carbohydrate spectrum and increased serum levels of liver enzymes in girls with menstrual cycle disorders are the basis for the formation of nonalcoholic fatty liver disease.

Precocious puberty (PP) is defined as the early development of secondary sexual characteristics (before the ages of 8 years in girls and 9 years in boys). The aim of this study is to identify characteristics of the dental maturity in girls with PP that discriminate them from normal healthy girls.This study included 99 girls aged 6 - 8 years with PP and 99 girls without past medical history of same chronological age (control group). The study was performed on 198 panoramic radiographs (99 PP girls, 99 control group girls). Demirjian method was used to evaluate the panoramic radiographs and determine dental maturity. Difference in dental maturity score and tooth formation stages between the two groups were analyzed.The PP group showed significant higher maturity score than control group. Among mandibular teeth, mandibular 2nd premolar and 2nd molar were significantly more mature in the PP group than control group. Logistic regression analysis showed that mandibular 2nd molar was only significant predictor for PP girls.

Objectives of the study: to investigate the peculiarities of the steroid hormone status in girls with menstrual function disorders, depending on comorbid psychopathology.Materials and methods. A total of 174 girls with menstrual function disorders (78 with abnormal uterine bleedings (AUB) and 96 with oligomenorrhea (OM)) were examined. The diagnosis of psychopathology was determined based on the clinical presentation at the time of examination. The comparison group consisted of 35 girls with a normal menstrual cycle.The laboratory examination included the assessment of estradiol, testosterone, cortisol (C), and dehydroepiandrosterone sulfate (DHEA-S) levels. The C/DHEA-S ratio was calculated using the unprocessed raw values. Results. Menstrual function disorders are often associated with hypoestrogenemia, a prevalent phenomenon. It was observed in almost a third of patients with AUB, whereas in girls with OM this number was significantly higher. Significant reduced values are found in girls with accompanying depressive states, especially in cases of AUB and OM. In instances of AUB and OM, the number of individuals with elevated levels of testosterone increased by 1.97–2.2 times in the presence of psychopathology. DHEA-S in patients with AUB was reduced in more than half of the girls, while in patients with OM it varies evenly in both directions, regardless of the presence or absence of psychopathology. A C level were more often reduced than increased, and achieves statistical significance when OM combined with neurotic disorders and AUB combined with depressive states. The C/DHEA-S ratio, as a stress indicator, was statistically significantly elevated in patients with AUB. This may suggest more pronounced manifestations of stress in patients with AUB than in girls with OM and a higher adaptability of the girls’ bodies with OM.Conclusions. Thus, the understanding of the role of reproductive steroids in the development of menstrual function disorders during adolescence has been deepened. Distinctive features of their interrelations in the presence of psychopathology have been identified. The impact of cortisol and DHEA-S, as well as C/DHEA-S ratio, on mental well-being in endocrine-related gynecological disorders in girls has been established

Objective — to identify the relationship between changes in the concentration of vitamins A, E, D, magnesium content, and comorbid pathology in adolescent girls with menstrual function disorders. Materials and methods. Examinations involved 237 girls with menstrual function disorders aged 11—18 years. Oligomenorrhea (OM) was diagnosed in 103 patients, and abnormal uterine bleeding (AUB) in 134 girls. Results and discussion. Comorbid pathology was revealed in most patients, regardless of the type of menstrual function disorder. Endocrine system disorders were the most frequent comorbidities. In girls with OM, comorbid endocrine disorders were accompanied by a decrease in the levels of vitamins A (pu < 0.01) and E, due to decrease in the frequency of their elevated indicators (pφ < 0.03). At the same time, mostly normal magnesium levels were registered (pφ < 0.001) due to a decrease in the frequency of its reduced and elevated levels compared to patients without pathology. In girls with AUB, comorbid endocrine system pathology was accompanied by decrease in the frequency of optimal levels of 25(OH)D3 (pφ < 0.03), and comorbid pathology of the neuro-­psychiatric sphere was accompanied by decrease in the frequency of elevated levels of vitamins A (pφ < 0.01) and E (pφ < 0.03) compared to girls without pathology. Regardless of the type of menstrual disorder, the greatest number of changes in the vitamin status were found in girls with comorbid pathology of the endocrine system. In patients with OM, the retinol levels were lower than in girls with AUB (pφ < 0.01), and a decrease in tocopherol levels was observed (pφ > 0.05). In girls with AUB, elevated levels of vitamin A (pφ < 0.03), vitamin E (pφ < 0.04), and moderate vitamin D deficiency (pφ < 0.03) were more frequently registered compared to girls with OM. Vitamin D deficiency in girls with abnormal uterine bleeding was less frequently registered compared to patients with oligomenorrhea (pφ < 0.05). It should be noted that comorbid pathology of the digestive system in abnormal uterine bleeding was mostly often accompanied by the decreased tocopherol levels (pφ < 0.05) and normal magnesium values (pφ < 0.04) compared to patients with oligomenorrhea. Conclusions. The study revealed a correlation between fluctuations in the content of vitamin status components and comorbid pathology in girls with menstrual disorders. The most pronounced changes in oligomenorrhea were found under conditions of concomitant pathology of the endocrine system, while in abnormal uterine bleeding, they were identified in the presence of endocrine disorders and disturbances in the neuro­psychiatric sphere. The combination of oligomenorrhea and endocrine pathology, as well as abnormal uterine bleeding and nervous disorders, is accompanied by a decrease in retinol and tocopherol reserves, creating conditions for the deterioration of compensatory­adaptive reactions of the body by suppressing the low-­molecular-­weight link of the antioxidant defense system. Abnormal uterine bleeding and concomitant endocrine disorders are associated with more pronounced moderate vitamin D deficiency.

Abnormal uterine bleeding (AUB) is one of the most common gynecologic complaints among reproductive-age women. The purpose of this study was to investigate the prevalence of AUB and its related factors among reproductive age Iranian women. A population-based cross-sectional study was conducted on 1393 women aged 15 - 45 years who participated in the Tehran Lipid and Glucose Study in 2009 - 2012. FIGO terminology and previous definitions were used for classification of AUB. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals to check the association between AUB and the women's demographic characteristics. P < 0.05 was considered statistically significant. A total of 35.8% (95% CI: 31.5% - 40.2%) of the participants suffered from one or more types of AUB. About 10.6% (95% CI: 6.3% - 12.5%) of them had disturbances of regularity and 23.8% (95% CI: 18.4% - 26.1%) reported experiencing disturbances of frequency. Also, disturbances of heaviness of flow and duration of flow were reported in 16% (95% CI: 12.7% - 19.2%) and 11.5% (95% CI: 8% - 15.4%), respectively. About 4.3% of the women (95% CI: 2.1% - 10.5%) reported irregular non-menstrual bleeding. According to previous definitions, the prevalence of heavy periods, metrorrhagia, polymenorrhea, oligomenorrhea, amenorrhea and inter-menstrual bleeding in reproductive aged women was 15.2%, 18.9%, 10.6%, 15.2%, 2.2%, and 4.3%, respectively. In addition, the proportions of women with AUB rose in the early and late reproductive years. After adjustment of confounders, logistic regression analysis showed that age (adjusted OR = 1.08, 95% CI: 1.07 - 3.97, P = 0.03) and BMI (adjusted OR = 1.05, 95% CI: 1.02 - 3.04, P = 0.04) had statistically significant associations with AUB. The prevalence of AUB as a possible clinical indicator of underlying disorders was high among Iranian reproductive age women. Healthcare providers and policy makers are required to acknowledge these disorders and provide education and counseling opportunities for the public to inform them when and how to seek medical advice.

Objective — to determine the nature of comorbid pathology in modern adolescent girls with disorders of menstrual function, and to establish the relationship between vitamin D status and comorbid pathology. Materials and methods. The analysis has been performed for the results of clinical and paraclinical examination of 333 adolescent girls aged 11—17 with menstrual disorders (primary oligomenorrhea and abnormal uterine bleeding). Physical and sexual development was determined, body mass index was calculated. The serum levels of vitamin D, prolactin, thyroid­stimulating hormone were evaluated. Results and discussion. Comorbid pathology was diagnosed in the absolute majority of adolescent girls with disorders of menstrual function, both of abnormal uterine bleeding (AUB) and oligomenorrhea (OM) types. Diseases of the endocrine system were registered mostly often; digestive pathologies and neuropsychological abnormalities were less common. In patients with OM, comorbid conditions of the digestive system and the neuropsychological area were registered significantly more often. Peculiarities of physical, sexual development, and menstrual function were established, which depended on the presence of various comorbid pathologies and the type of menstrual function disorders. Vitamin D insufficiency and its deficiency were observed in the majority of girls with both AUB and OM, and no significant difference was found in various comorbid pathologies. Normative values of vitamin D were noted in no more than 12—18 % of cases and tended to decrease in presence of the diseases of endocrine system. Conclusions. The obtained results demonstrated the importance of a multidisciplinary approach to the examination of patients with menstrual cycle disorders, as a guarantee of increasing the effectiveness of treatment and preventive measures with the aim of restoring reproductive potential.

Background. The reproductive health of girls has acquired great social significance in connection with the problem of quantitative and qualitative reproduction of the population. The purpose of the study was to determine the hormonal status of adolescent females with menstrual disorders and various somatic pathologies and to investigate the state of adaptive-compensatory capacities in these patients. Materials and methods. The hormonal background was studied in 391 girls aged 12–17 years: 175 with abnormal uterine bleeding (AUB) and 216 with oligomenorrhea (OM). All patients were examined by a multidisciplinary team. Results. A comorbid pathology was found in the absolute majority of girls with menstrual abnormalities. Endocrine disorders were noted more often (pϕ &lt; 0.001–0.00001). Indicators of hormone concentration in patients with menstrual disorders had no significant differences depending on the type of comorbidity. Probable changes in the content of some hormones were observed depending on the type of menstrual disorders. A significant increase in the level of luteinizing hormone (pu &lt; 0.02) and a decrease in estradiol (pu &lt; 0.02) were observed in patients with OM compared to those with AUB. The assessment of the adjustment state revealed that in girls with menstrual disorders, the average cortisol content did not differ from that of controls, and insulin was higher than in the comparison group (pu &lt; 0.001). Ho­wever, high cortisol values (above 90 percentile) were noted in 8–13 % of patients with AUB and OM. The stress index (C/In) as a marker of a nonspecific stress response was lower than in the comparison group (pu &lt; 0.0001), and it was probably higher in girls with OM than in adolescents with AUB (pu &lt; 0.004). Conclusions. An interdisciplinary approach is a mo­dern strategy in the treatment of menstrual disorders in adolescence. A decrease in the stress index was found in girls with menstrual disorders, which may indicate a decrease in adaptive capacity. Moreover, adolescents with OM are more adjusted to menstrual disorders than girls with AUB.

BackgroundEarly sexual maturation has been associated with overweight that may persist after the completion of biological growth and development. We have prospectively examined the influence of early sexual maturation on subsequent overweight in late adolescence and assessed if this association was modified by central adiposity in early adolescence.Methods1605 Norwegian adolescents were followed from early (baseline, mean age 14.2 years) to late adolescence (follow-up, mean age 18.2 years). Maturational timing was assessed by self-reports of pubertal status (PDS) in boys and age at menarche (AAM) in girls. Central adiposity was classified according to waist circumference (waist) measured at baseline, using age and gender specific medians as cut off. Overweight was classified according to International Obesity Task Force (IOTF) standards.ResultsAt follow-up, early sexual maturation in girls, but not in boys, was associated with overweight. This association, however, was restricted to girls with high waist circumference (> median) at baseline (OR, 2.7, 95% CI 1.5–4.9). Thus, age at menarche was not associated with overweight in girls with low waist (≤ median) at baseline. Central adiposity was, independent of maturational timing, associated with higher BMI at follow-up in both genders, but differences were more pronounced among early matured girls (3.5 kg/m2), than among intermediate (2.7 kg/m2) and late matured girls (1.2 kg/m2).ConclusionIn girls, the combination of central adiposity and early age at menarche appears to increase the risk of being overweight in late adolescence.

The pubertal period is accompanied by the tension of the adaptation system during the hormonal adjustment. Purpose - to define the hormonal determinants of stress-related menstrual disorders in adolescent girls with comorbid mental disorders and the peculiarities of adaptation reactions. Materials and methods. 150 adolescent girls with menstrual cycle disorders were examined. The levels of luteotropic hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), estradiol (E2), testosterone (T), cortisol (K), dehydroepiandrosterone sulfate (DHEA-S) were determined. They were divided into three groups depending on the examination by a psychiatrist: without mental status disorders, with anxiety-phobic disorders and depressive states. The control group included 35 girls of similar age with a normal menstrual cycle who were examined in the early follicular phase. Results. There were no significant differences in the content of gonadotropic hormones in girls with menstrual function disorders in view of the state of mental health. However, in girls with oligomenorrhea (OM), in relation to patients with abnormal uterine bleeding (AUB), elevated LH values are significantly more often registered (p&lt;0.03). Levels of peripheral T, as well as its precursor DHEA-S and metabolite (E2), were associated with mental health status. The lowering of E2 significantly elevated in adolescents with comorbid psychopathology. The number of girls with high T values increased in the presence of psychopathology in AUB and remained unchanged in OM. Cortisol in psychopathology, regardless of the type of menstrual function disorders, was reduced in relation to the control group, however, in girls with OM, its content was significantly higher, especially in depressive states (p˂0.05). The specific gravity of girls with a reduced level of DHEA-S in patients with AUB increased with comorbid psychopathology. In case of OM, a reduced and increased content of DHEA-S was registered with the same frequency. An increase in the C/DHEA-S indicator of the functioning of the hypothalamic-pituitary-adrenal system in patients with OM was noted much less frequently than in patients with AUB (p˂0.006). Conclusions. It is believed that the hormonal relationship between cortisol and DHEA-S indicates the body’s response to stressors and can be used as one of the biomarkers of neurotic and depressive states. An increase in the C/DHEA-S ratio suggests a possible dissociation of their secretion. Adolescents with AUB, unlike girls with OM, have a decrease in the “protective” hormone DHEA-S, which can affect the deterioration of mental health. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Mccune Albright Syndrome and Polycystic Ovary Syndrome in a Single Individual

Objective — to determine predictive factors in the families of girls with menstrual disorders comorbid with endocrine system pathology. Materials and methods. The genealogical analysis was carried out in the families of 47 girls with oligomenorrhea (OM) and 44 girls with abnormal uterine bleeding (AUB) comorbid with endocrine system pathology. The comparison group consisted of the pedigrees of 30 families of healthy girls living in Kharkiv and Kharkiv Region. During the genealogical study, we observed the principles of the Declaration of Helsinki, the Council of Europe Convention for the Protection of Human Rights and Dignity of the Human Being, and the relevant laws of Ukraine. The Student’s t­test was used to determine the significance of the differences between the signs. The predictive implications of the studied signs were determined by the Wald method with informativity estimation using the Kullback criterion. Results and discussion. Hereditary burden of reproductive, gynecological non­inflammatory, endocrine diseases and environmental factors was identified in the families of girls with OM and AUB comorbid with endocrine pathology: pernicious habits and stress in the mothers of sick girls before and during pregnancy, threatened miscarriage. Risk factors for the sick girls included artificial feeding of a girl, stress, traumatizing of a girl, and prolonged use of the Internet and gadgets. Among non­communicable diseases in relatives of sick girls, the most common were gynecological non­inflam­matory diseases when compared with the relatives of girls with AUB and healthy girls (p &lt; 0.001), while relatives of healthy girls mostly suffered from nervous system disorders (p &lt; 0.05). Common and distinct predictive signs in the families of girls with OM and AUB and comorbid endocrine pathology have been identified. Conclusions. The predictive factors in the families of girls with OM and AUB have been identified, the use of which will allow forming high-risk groups as regards the high risk of menstrual disorders based on the genealogical analysis.

Background: In spite of the presence of menstrual dysfunctions in female student athletes, few studies have been conducted to analyse the reasons and athletic factors affecting them. Regional distribution of fat is one of the important factors that plays a role in causing menstrual disorders, and since menstrual cycle disorders can lead to many problems, the present study was aimed to compare and analyse the menstrual dysfunctions and regional patterns of fat distribution in female student athletes and non-athletes. Methods: The present study was descriptive analytical which was carried out on 206 female student athletes and non-athletes studying in Shahid Madani University of Azarbaijan selected through convenience sampling in 2013. Subcutaneous fat was measured using calipers and a questionnaire was given to subjects in order to collect their personal and their menstrual cycles’ information. The collected data were analysed by SPSS (version 16) statistical software. Results: The findings of the study revealed a significant difference between athletes and non-athletes in terms of the incidence of menstrual dysfunctions of amenorrhea, oligomenorrhea, menorrhagia, hypomenorhea and hypermenorrhea (p<0.05). Moreover, there was a negative relationship between thigh fat and amenorrhea (p=0.024), suprailiac and menorrhagia (p=0.015), chest and hypomenorhea (p=0.033), and waist circumference and hypermenorhea (p=0.011) in athletes. Conclusion: Overall, the findings of this study showed that prevalence of menstrual disorders was higher in athletes than non-athletes and low distribution of fat in the lower region of athletes’ body may be disturbed during menstrual periods (amenorrhea) and low distribution of fat in the abdominal and upper parts of body may lead to irregular uterine bleeding (menorrhagia, hypomenorhea and hypermenorhea).

Menarcheal age is the most important measure of sexual maturation in girls and a sensitive indicator of environmental conditions during childhood. The study analysed the association between age at menarche and socio-economic characteristics (urbanization, population size, education of parents and number of children in the family). Questionnaire data were collected from 3271 female schoolchildren born between 1981 and 1984, living in three provinces of southern Poland. Menarcheal age was estimated by the recall method and based on the date of menarche given by the study participants. ANCOVA and multiple regression analyses were applied to test statistical significance of differences between groups. Girls from families with high socio-economic status experience menarche at an earlier age than girls from families with lower socio-economic status. However, depending on the geographical region and the population size, other factors influence menarcheal age. In the Krakow province, factors that significantly differentiate age at menarche are urbanization, father's education and number of children in the family; in the Opole province, these factors include urbanization and number of children in the family, while in the Nowy Sacz province, number of children in the family is significant. Socio-economic differences are greater in a large urban city (Krakow), and affect variation in age at menarche. However, within smaller populations (Opole, Nowy Sacz) living in towns and villages, the difference in age at menarche is less visible. In addition, variation between areas reveals a lower age at menarche in urban as compared with non-urban areas.