UDC 61

DISORDERS OF MENSTRUAL FUNCTION DEVELOPING IN GIRLS WITH

OBESITY
Bodnariuk Oksana Ivanivna
Candidate of Medical Sciences, Associate Professor of Obstetrics and Gynecology
Department at Bukovinian State Medical University, Chernivtsi, Ukraine
Borshulyak Alla Anatoliivna
Lecturer at Kamianets-Podilskyi Medical College
Kamianets-Podilskyi, Ukraine
Toporivska Yelyzaveta Mykolaivna
Student at Bukovinian State Medical University, Chernivtsi, Ukraine.
oksana-bodnarjuk@bsmu.edu.ua
toporivska.yelyzaveta.mf1@bsmu.edu.ua

Annotation: Adolescence is particularly important for the health of girls. The harmonious
development during childhood and adolescence determines many aspects of a woman's life
in both medical-biological and social aspects. Despite the use of modern diagnostic and
therapeutic measures, the quality of women's reproductive health remains low. Therefore,
there is a growing need to improve reproductive health care at earlier stages of a woman's
life. [1] Adolescence is a transitional period between childhood and adulthood. Obesity is a
chronic relapsing disease characterized by excess accumulation of adipose tissue in the body,
caused by metabolic disorders. It is based on a positive energy balance, which means that the
energy intake from food calories exceeds energy expenditure. [1,2]
Body weight plays a significant role in the development of menstrual function. It is known
that adipose tissue is involved in regulating the menstrual cycle, as female sex hormones are
also synthesized in it. Increased amount of adipose tissue (over 15-20%) leads to disruptions
in the "hypothalamus-pituitary-ovary" system and can be a factor in the development of
polycystic ovary syndrome (PCOS), hyperplastic processes of the endometrium, infertility,
miscarriage, preeclampsia, fetal growth restriction. According to various authors, timely
onset of menarche in women with different forms of obesity and reproductive dysfunction is
observed only in 31% of cases (Paenok O.S., 2014). The establishment of menstrual function
significantly affects the reproductive system, although data on the peculiarities of
reproductive function in obesity are quite controversial [3,4].
According to the NHANES (National Health and Nutrition Examination Survey) study
conducted in 2011-2012, the proportion of people aged 20 to 39 with obesity was 31% (BMI
≥ 30 kg/m2); the highest prevalence was among African American women (56.6%). For
comparison, in 1980 (before the routine use of the BMI indicator), only 7% of women with a
body weight of more than 95 kg were noted at the first prenatal visit [5].

Adverse factors associated with obesity lead to disturbances in ovarian function and lower
the quality of oocytes. Additionally, there may be a negative impact on the receptor
apparatus of the endometrium. Some studies have demonstrated that weight loss contributes
to improving hormonal changes and fertility in women with obesity. However, large
randomized studies are needed to confirm these preliminary observations [4,6].
Adipose tissue is capable of depositing steroids due to their high solubility in lipids, so the
total pool of sex hormones in the body, including androgens, is much higher in obese
patients than in people with normal weight. Additionally, in adipose tissue, there is active
conversion of androstenedione into estrone and testosterone by aromatase and 17-beta-
hydroxysteroid dehydrogenase, respectively, which is partially associated with functional
hyperestrogenism and hyperandrogenism in patients with obesity[2].
In addition to menstrual dysfunction, adolescent girls with obesity are at risk for conditions
such as polycystic ovary syndrome, virilization, and hyperplastic processes in hormonal-
dependent organs and tissues[3].
Despite the complexity of the reproductive system, the main form of its disruption is a
disturbance in the menstrual cycle, from amenorrhea to acyclic uterine bleeding [7]. It is
known that obesity leads to insulin resistance, resulting in hyperinsulinemia [8]. The ovarian
theca cells have insulin receptors, and insulin also increases the production of insulin-like
growth factor-1 (IGF-1), which enhances androgen synthesis in the ovarian theca cells and
interstitial tissue. Insulin also decreases the level of sex hormone-binding globulin and thus
increases the level of free, biologically active testosterone [9].
The diagnosis of polycystic ovary syndrome (PCOS) is based on clinical data - a menstrual
cycle longer than 42 days. The echographic picture most often characterizes the ovaries as
multifollicular structures, with an increase in ovarian volume, and can be signs of a chronic
anovulatory state.
PCOS often appears as a symptom of a disease. Pronounced hormonal disturbances are noted
in girls with obesity two years after the onset of menstruation: testosterone and LH levels are
above the 95th percentile. In PCOS developing against a background of obesity, hirsutism is
observed in more than 35% of cases, fatty seborrhea and acne - in almost 20% of cases [10].

The aim of the study is to improve the methods of diagnosing menstrual dysfunction in girls
with excessive body weight by assessing clinical and anamnestic markers, with the goal of
developing a diagnostic algorithm and pathogenetically justified correction of menstrual
cycle disorders.
Key words: adolescence, girls' health, development, reproductive health, protection of
reproductive functions, obesity, overweight, adipose tissue, menstrual function,
hypothalamus-pituitary-ovarian system, polycystic ovary syndrome, infertility, reproductive
system.
Materials and methods. To achieve the stated goal and implement the assigned tasks, a
comprehensive clinical and laboratory examination was conducted on 79 patients with
menstrual cycle disorders on the background of obesity aged 12-18 years with complaints of
menstrual dysfunction and delayed menstruation up to 5 months, and 31 girls of the same
age with a regular menstrual cycle (control group). The parents of minors provided written
consent for their children to participate in clinical trials. The patient's informed consent form
and patient examination card were approved by the Biomedical Ethics Commission of the
Bukovinian State Medical University (BSMU) of the Ministry of Health of Ukraine
(Chernivtsi).
The clinical examination included an analysis of the patients' complaints, collection of the
disease history (perinatal, somatic, gynecological, clarification of the state of menstrual
function and reproductive system in close relatives). The upbringing conditions of the girls,
the presence of additional loads, dietary disorders, and harmful habits were analyzed.
All patients underwent standard general clinical and special gynecological examinations.

Results of the research and their discussion. The onset of menarche in the control group
was between 12 and 14 years, which corresponds to normal terms, while in the group of girls
with obesity, almost half of the patients (53.3%) had delayed onset of the first menstruation,
and menarche began after 14 years, which was 5 times more often than in the control group.
As a result of the conducted research, it was established that the average age (M ± m; δ) in
adolescent girls of the control group (13.7 ± 0.07; 0.5 years), adolescent girls with menstrual
cycle disorders against the background of obesity (13.2 ± 0.07; 0.5 years) were similar
(p>0.1). The frequency of complaints of adolescent girls in the main group about menstrual
delay from 42 days to 6 months was (126.7 ± 2.5; 5.1 days), (p<0.05). The duration of
menstruation (M ± m; δ) in girls of group 1 was 2.1 ± 0.05, and it was significantly shorter
than in girls of the control group - 4.1 ± 0.05 days (p<0.05). The menstrual flow volume (M
± m; δ), determined by the method of Yanssen J.R. (2001), in girls of the main group was
10.2 ± 0.05; 0.4 score (on average 1-2 pads per day) and was significantly lower than in girls
of the control group - 17.3 ± 0.07; 1.5 score (2-3 pads per day) (p<0.05). Table 1 shows
complaints and clinical features in patients in the examined groups.
Acne of varying degrees of severity was detected in 28 (35.4%) girls in the main group,
significantly more often than in the control group - 4 (12.9%). It should be noted that in the
control group, acne was associated with the dynamics of the menstrual cycle, that is, it
worsened or appeared before menstruation. In contrast to this, in examined girls with
menstrual cycle disorders against the background of obesity, there was no menstrual
dynamics of acne. Moderate hirsutism was more often noted in girls of the main group
(hirsutism score (HS) 15.6 ± 1.6 points) than in the control group (HS - 9.2 ± 1.1 points)
(p<0.05).
In the clinical picture of PMF (premenstrual syndrome), which developed against the
background of obesity (43.03%), emotional lability was present (sharp mood swings,
negative and asthenic experiences, feelings of somatic discomfort, conflict, fatigue due to
low tolerance to stressors), which may complicate the course of the disease. This is likely
related to the fact that the reproductive system has common executive mechanisms with
other functional systems, such as the cardiovascular, respiratory, emotional-motivational,
and others. Menstrual morbidity was noted in 48.1% of girls in the main group (p>0.1). In
the control group, signs of menstrual discomfort were absent. Thus, complaints about
irregular menstrual cycles and delays of 42 days to 6 months were observed in 100% of girls
in the main group. In addition, the duration and abundance of menstruation were
significantly shorter and lower, respectively, in the main group than in the control group. The
presence of clinical signs of hyperandrogenism was noted in 32.9% of adolescent girls with
obesity, which is 5 times more common than in girls without excess weight and with a
normal menstrual cycle.

At the time of seeking medical attention, girls with obesity most commonly complained of
menstrual delays of 1-2 months. Menstrual delays of 2-3 months were observed in every
third patient with obesity. Menstrual delays of 3-4 months were noted in 20.25% of girls
with obesity, and only 7 (8.85%) patients were concerned about the absence of menstruation
for 4 to 5.5 months.

Due to the fact that habits of dietary behavior and physical activity affect weight gain, we
studied this issue. In assessing dietary behavior, it was found that patients with obesity ate
irregularly more often compared to teenage girls with a normal BMI, and their most calorie-
dense meal was dinner. Significant differences were found compared to the comparison
group of patients. Eating was combined with other activities (reading, playing video games,
communicating on social networks, watching television) with the same frequency in both
groups, but physical activity was significantly lower in the group of girls with obesity. It was
found that patients with obesity, unlike the control group, eat irregularly three times more
often, and their most calorie-dense meal is twice as likely to be dinner, and physical activity
is almost two times lower than in the control group. These factors are also pathogenic in the
mechanism of obesity development in our patients.

Ultrasound of the organs of the small pelvis (SPO), particularly the measurement of the size
of the uterus and ovaries, is considered the "gold standard" in pediatric gynecology, which
allows timely diagnosis of various gynecological pathologies and appropriate correction in
the treatment regimen.
It was found that the average size of the uterus in patients with menstrual cycle disorders on
the background of obesity was lower than in girls in the control group without signs of
menstrual cycle disorders. Also, in the main group of patients, a decrease in all parameters of
the size of the uterus compared to the control group of girls was noted.
Hypoplasia of the uterus was observed in almost every second patient with menstrual cycle
disorders on the background of obesity (36, 45.46%).

When analyzing the structure of the ovaries using ultrasound data, it was established that in
adolescent girls with menstrual disorders (PMCs) and obesity, the echographic structure of
the ovaries was characterized by a multifollicular structure - diffuse arrangement of follicles
with a medium diameter of 1.2 ± 0.12 cm on the background of increased ovarian volume.
The identified echographic changes in the structural morphology of the ovaries may be early
signs of polycystic ovary syndrome in adolescent girls with menstrual disorders and obesity,
regardless of clinical form. Adipose tissue participates in the metabolism of sex steroids and
independently produces a number of adipokines and hormones such as leptin, adiponectin,
TNF-α, IL-6, and their soluble receptors [2,11]. BMI is a predictor of changes in leptin
levels, and therefore, Lee H., Reed D.R. [2001] proposed using the Leptin / BMI index (L /
BMI) as an indicator of leptin resistance. As a result of this research fragment, we
established hyperleptinemia and leptin resistance in patients with PMC and obesity. In the
control group, leptin and L/BMI levels did not exceed the norms. Hyperleptinemia is
accompanied by hyperinsulinemia and insulin resistance. Therefore, hyperleptinemia and
leptin resistance in patients of the first group can be associated with hyperinsulinemia and
insulin resistance, which is confirmed by established correlation relationships between leptin
and HOMA-IR (ρ = 0.65), the ratio of L/BMI and the Karo index (ρ = 0.8) (p <0.05).

Conclusions. Primary menstrual dysfunction in the context of obesity occupies one of the
leading positions among menstrual dysfunctions in adolescent girls and accounts for 7.6% of
gynecological diseases, indicating the need to improve therapeutic and preventive measures
aimed at timely correction of their reproductive and somatic health disorders.
Therefore, determining the serum adiponectin level in adolescents with PMD in the context
of obesity can improve the diagnosis of insulin resistance and refine the course of ovarian
dysfunction, optimize therapeutic tactics, and forecast the restoration of menstrual function.