Keywords
adolescence, reasons for examination, menstrual disorders, contraception
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
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distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Adolescence is a period of rapid physical development triggering the simultaneous secretion of
various growth hormones, sexual and thyroid hormones [1]. This period occurs in people aged
between 10 and 19 years, in about 18% of the world’s population and this period between child-
hood and adolescence, which causes physiological, psychological changes, and various other
health problems and problems of menstruation, is of major importance [2]. During childhood
and adolescence, it is necessary for the doctor to have appropriate behavior towards the young
girl and the parents when taking history and during gynecological examination. In general, it
has been found that all mothers co work to obtain information, but there is some mistrust and
skepticism about gynecological examination. This mistrust largely subsides after discussions,
in an appropriately configured practice environment, but in a small percentage it remains
accompanied by fear and, even less, it turns into neglect in the gynecological examination. The
usual reasons why young girls visit the teenage gynecology clinic are as following: amenor -
rhea, dysfunctional bleeding, lower abdominal pain, to avoid pregnancy due to the presence
and association to great problems, great early development of genital organs, breasts, hirsut-
ism, genital anatomy outgrowth, excretion from breast nipple, symptoms from the urethra or
bowel, irritation and redness in the vulva, and pain or palpable lymph nodes in the vulva [3, 4].
2. Amenorrhea
The main process that marks the start of adolescence is the onset of pulsatile excretion of
GNRH. Breast growth (thelarche) is the first natural characteristic of puberty and occurs nor-
mally in the 11th year whereas the menstrual is expected to be shown 1 year later. A range of
variations in the normal sequence of events among the different populations is observed. In
general, significant role plays the body weight and the nutritional balance [ 5, 6]. Typically,
menstruation begins after 2–3 years of thelarche at Tanner IV breast stage and rarely at Tanner
III stage. Approximately, 96–97% of adolescent women will have menstruation at the age of
15 [6]. During the first year after menstruation, 50% of the cycles are anovulatory, also during
the next 2 years, the intervals between the menstrual cycles show wide variations ranging
between 21 and 45 days. The classic definition of amenorrhea includes the absence of men -
struation after the 15th year. It is distinguished in primary with or without breast growth and
secondary. Amenorrhea in adolescence is a reasonable concern regarding the thorough inves-
tigation in order to find the diagnosis and future fertility prognosis. Before the beginning of
any hormonal therapy, it is necessary to exclude a certain number of pathological conditions
in order to avoid a delayed diagnosis of all causes that in the mature reproductive age will be
characterized as infertility [ 5]. In the case of primary amenorrhea without the development
of secondary sex characteristics, the diagnosis can be made earlier, by the completion of the
13th year and is indicative of hypogonadism [5, 7]. The occurrence of primary amenorrhea is
a disruption of the interaction of a large complex of processes that contribute to the appear -
ance and normal continuance of menstruation such as normal chromosomal composition,
the presence of a functioning hypothalamic-pituitary-ovarian axis, the normal endometrial
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response, the anatomical integrity of the entire path of the output of the menstrual content,
and sufficient supportive function of other endocrine glands such as thyroid gland and adre-
nal glands. In the primary amenorrhea of adolescents, there is an increased probability that
the underlying pathology is the result of congenital malformations of the genital organs (60%)
or endocrine disorders (40%). The most common causes of primary amenorrhea are normal
delay, important weight loss, intense exercise, and virginity hymen atresia.
2.1. Clinical indications for investigation of amenorrhea in adolescence
Absence of menstruation at 15 years (complete development of the secondary sex character -
istics) is an indication of amenorrhea investigation Absence of menstruation at 13 years with
simultaneous absence of secondary sex characteristics (non-start breast growth) (delayed
puberty) should also be investigated [8–10]. Lastly, absence of menstruation at 14 years with
simultaneous coexistence of clinical disorders, such as nutritional disorders and clinical signs
of hyperandrogenism needs further investigation.
Secondary amenorrhea is characterized by the absence of menstruation for 6 months in teens
who previously had an unstable menstrual cycle for three or more consecutive cycles, in ado-
lescents with a previous cycle of 21–45 days, and generally the interruption of menstruation
since it had previously begun [8–11]. The most frequent cause of secondary amenorrhea is the
polycystic ovary syndrome (PCOS). The most common symptoms are infertility because of
anovulation and hyperprolactinemia. Regardless of the type of amenorrhea, the presence of
hypertrichosis and galactorrhea, the possibility of pregnancy, the pelvic pain as well as the
history of sexual contacts should be thoroughly investigated. Other parameters to be inves -
tigated also include height, body mass index, nutritional balance and estradiol, prolactin,
testosterone, AMH and FSH levels. The above investigation is considered really useful for the
diagnosis of underlying pathology and the distinction between hypogonadotropic hypogo -
nadism (HH) and amenorrhea due to primary ovarian failure. At this point, hormone control
plays an important role. Low levels of FSH, LH, and E2 are indicative of hypothalamic dam -
age. High level of FSH and LH and low levels E2 are indicative of ovarian damage. High level
of prolactin is indicative of prolactinoma [10–12].
The hypogonadotropic hypogonadism (HH) (hypothalamic amenorrhea) is accompanied by
low levels of FSH and E2 and can be hereditary or acquired, organic or functional. In primary
amenorrhea, the origin is usually genetic or even organic and the corresponding hypotha -
lamic functional etiology is very rare [13–15]. In the last case, absence or delayed development
of secondary sex characteristics is very helpful for the distinction. In the case of hypogonado-
tropic hypogonadism, it is necessary to perform pituitary imaging to exclude or diagnose
neoplastic pathology.
If the imaging test is negative, then hypogonadotropic hypogonadism may be congenital, func-
tional, attributed to absorption disorders, or ultimately due to chronic underlying pathology
(renal or hepatic failure) [ 13–15]. The congenital hypogonadotropic hypogonadism is statis -
tically very rare. It may be appeared as independent pathological entity or associated with
pituitary insufficiency, either primary or as a demonstration of a syndrome. Independent HH
occurs in 90% of cases with primary amenorrhea and is accompanied by absence or delayed
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development of secondary sex features [13–15]. The careful investigation of clinical signs and
symptoms such as anosmia or hypoxia when combined with congenital disorders in the palate
or teeth is considered necessary because they may be manifestations of Kallman’syndrome. In
the case of hypoxia absence, some mutations that adversely affect the functioning of the hypo-
thalamus may be responsible [14–16]. Moreover, some congenital HHs may be associated with
other disorders of pituitary function and morphological abnormalities such as the presence of
ectopic pituitary tissue. Genetic mutations and polymorphisms are also involved in these cases.
In obese adolescents with amenorrhea, some rare genetic variations regarding the leptin gene
or its receptor have been described. Finally, congenital HHs may be a part of various syn -
dromes such as Prader Willi and Bardet-Biedl.
The functional hypothalamic amenorrhea is usually secondary. The abnormal background is
often associated with nutritional disorders mainly related to lipid metabolism. This particular
pathological condition can be a part of a chronic pathological process or a severe emotional
episode that blocks the pulsatile secretion of GNRH. The first priority in case of primary
amenorrhea with normal development of secondary sex features is the exclusion of pelvic
pain. That is the reason why it is widely recommended application of pelvic ultrasound as
well as hormone control (testosterone, estradiol, and FSH) [13–15].
When pain is observed, the possible causes may be vaginal aplasia, presence of a transverse
diaphragm covering the vagina, and more often the virginity hymen atresia. In these cases,
clinical examination of the abdominal wall reveals the existence of a painful mass that may
be caused by the distension of the endometrial cavity (hematometra). Presence of blood in
the vagina may also be seen. Ultrasound and MRI examinations always confirm the primary
diagnosis [13–15].
When there is no pain, the possible diagnosis is uterine aplasia accompanied in many cases by
vaginal aplasia as in Rokitansky syndrome. The incidence is very rare, 1/4000–1/5000 [13–15].
It is a syndrome that reflects abnormal development of Muller’s ducts and sometimes abnor-
malities of the urinary tract, musculoskeletal as well as heart disorders are also observed.
Levels of FSH, LH, estradiol, and testosterone hormones are normal. The ultrasound confirms
the absence of uterus [ 12–14]. Karyotype is always XX. The differential diagnosis of uterine
aplasia includes androgen resistance syndrome, which is caused by mutations in testosterone
receptors, high plasma testosterone levels, and concomitant tubal aplasia as well as aplasia of
the upper part of the vagina. Karyotype in these cases is XY.
In the case of painless amenorrhea, with existing uterus confirmed by ultrasound and normal
breast growth, the most probable cause is polycystic ovary syndrome.
Finally, according to a review of the American Reproductive Society, 40% of primary amenor-
rhea is accompanied by the absence of secondary sex characteristics and high levels of gonad-
otropins, 30% are due to the absence of secondary sexual characteristics and low levels of
gonadotropins and 30% are present with normal breast growth [17].
Secondary amenorrhea is characterized by the absence of menstruation for a period of at least
3 months in previously normally menstruating adolescents. In any case, the possibility of
pregnancy must first be excluded.
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It is also necessary to investigate the history of secondary sex characteristics develop -
ment, the nutritional balance, the psychological status, the weight ups and downs and the
physical fitness, or the presence of hyperandrogenic signs and the rapid increase of weight
during puberty. Special points are also hyperinsulinemia, galactorrhea-indicative sign of
hyperprolactinemia, signs of hypercortisonemia, and black nozzle in the neck. Coexistence
of hyperandrogenism is confirmed by elevated levels of total testosterone as well as of
17-OH-progesterone. In cases that confirmed the lack of hyperandrogenic signs, proges -
terone test, control of E2, prolactin, and FSH levels can be used for the determination of
diagnosis. Oligomenorrhea (less than 8 cycles during a year) undoubtedly raises the inter -
est for further investigation. The most frequent causes of secondary amenorrhea are func -
tional hypothalamic disorders and polycystic ovarian syndrome. Finally, the diagnostic plan
should always include the exclusion of less common causes that may also contribute to the
demonstration of oligomenorrhea [ 10–15].
2.2. Therapy
Therapy should be mainly based on the underlying cause. If any barrier exists to menstrual
flow, surgery is inevitable. It is also necessary to surgically remove androgen-secreting tumors
that may be located either in the ovaries or in adrenal glands. Non -pharmaceutical hyper -
prolactinemia should be treated by dopaminergic agonists. When amenorrhea is caused by
functional hypothalamic etiology, the treatment should include changes in dietary habits and
possible special psychological support. All other cases, except of Rokitansky and the andro -
gen resistance syndrome where there is no hormonal disorder, require hormonal therapy.
The main target is either to restore estrogen deficiency or to prevent endometrial hyperplasia
in cases of anovulatory cycles [10–16]. Replacement treatment also aims to prevent distressing
consequences such as osteoporosis and cardiovascular diseases.
When primary amenorrhea is not accompanied by development of secondary sex charac -
teristics, treatment initially includes the administration of small doses of estrogen to induce
puberty onset. It is then required to progressively increase the above doses until satisfactory
breast growth is achieved. After the second year, it is recommended to add progestogen for
at least 10 days/cycle.
When amenorrhea is secondary with normal development of secondary sex characteristics,
progestogen is used to assess endogenous estrogen production. The positive test indicates
adequate estrogen production and 10 days administration of progestogen allows the cycle’s
normalization. If the test is negative and there is also a need, treatment with contraception
can be administrated starting with a low dose. Basic condition is the absence of any familiar
history of thromboembolic events. If contraception is not desired, then replacement therapy
is administered. This includes 17β-estradiol either orally, as skin patch, or as gel for 25 days/
cycle and progestogen 10–12 days/cycle. In case of hyperandrogenism in PCO syndrome, the
administration of acetate cyproterone at a dose of 50 mg/day is recommended for 21 days/
month in combination with 17β-estradiol.
The presence of amenorrhea in adolescence should not be underestimated. It is advisable to
investigate amenorrhea either after the 15th year or 3 years after breast growth has started.
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The clinical examination always evaluates BMI, height, any hyperandrogenic, or galactor -
rhea signs. Laboratory investigations include estradiol, hCG, FSH as well as testosterone, and
17-OH progesterone levels.
Early diagnosis of genetic causes of hypogonadotropic hypogonadism occurs at <40%. The
identification of new genes may improve the scientific knowledge in the function of hypotha-
lamic-pituitary-ovarian axis during puberty.
In the case of hypogonadism, long-term hormone replacement therapy is recommended and
sometimes psychological support is also required.
3. Polycystic ovary syndrome (PCOS)
The most frequent hormonal disorder in reproductive age’s women with oligo or anovula -
tion and hyperandrogenemia is associated with PCOS in the majority of cases. Many factors
such as psychological, social, and economic could play role in the disorder of the syndrome.
Moreover, the association of PCOS with metabolic syndrome and its effects represent a new
challenge of interest of the syndromes in the general population. The major symptoms are:
a. Hyperandrogenemia or hyperandrogenism
b. Oligo or anovulation
c. Polycystic appearance of the ovaries during sonography [18, 19].
In PCOS, many symptoms included hirsutism, acne, alopecia, acanthosis nigricans, and obe -
sity that are also linked to hyperinsulinemia [18–20]. One of seven teenagers (13%) has a major
health problem because of obesity. Obesity is a major health problem affecting approximately
13% of teenagers. Normal body mass index (BMI) values range from 19 to 24.9 kg/m2. Body
mass index 40 kg/m2 characterizes severely obese individuals. Menstrual cycle disorders are related
to obesity in childhood and in young women. As the abdominal adipose tissue increases,
increment of androgens aromatization is observed and subsequent endocrine abnormalities
are appeared. Obesity is an independent factor aggravating PCOS endocrine abnormalities
as subcutaneous abdominal tissue and liver contributes to extragonadal aromatization [ 21].
Obese women with PCOS have two types of insulin resistance, one related to the syndrome
and the other related to obesity. The pancreas is involved in the mechanism of insulin resis -
tance by increasing the release of insulin, which leads to stabilization of the glucose level
in the early stage of the disease [ 21]. During pregnancy, the morbitity is increased with an
increase in labor induction, urgent cesarean section, dystocia and abnormal presentation. The
neonates are generally overweight and the risk for fetal death is increased. Moreover, diabe -
tes during pregnancy is increased and needs follow-up. Recent data show an increased rate
of overweight and obese women, specifically in the United States of the female population
(64.1%) and obese women remain high (35.5%). In Europe, there is a diversity depending of
the countries: low rate (6.2%) in Western and Northern Europe, high rate in Central, East and
South Europe (36.5%). Oral contraceptives are the major treatment of PCOS decreasing all the
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clinical symptoms and the level of androgens. In obese adolescence, the oral contraceptive
pills have a different pharmacokinetic profile with a decrease of the estrogens and progesto -
gen clearance, but in contrary an increased SHBG was observed [22–26].
Contraceptive pills constitute the cornerstone of hormone therapy, as they promote reduction
of hyperandrogenemia, hirsutism, and acne [27].
Therefore, there is a typical decreased effectiveness of contraceptive pills in obese adolescents,
despite there are superior to the contraception with condoms.
3.1. Therapeutical strategy
Any other known disorders, that they are possible to cause hyperandrogenemia and oligo
or amenorrhea have to be excluded. These are often associated with: nutrition, exercise,
menstrual disorder treatment, metabolic syndrome and diabetes drug treatment and can be
treated by contraceptive pills having progestagen with antiandrogenic action, as cyproterone
acetate, dienogest, drospirenone [28, 29].
3.2. Functional uterine bleeding in adolescence
In adolescence, it is quite possible a disorder of negative regression of gonadotropins by
gonadal steroids to be happened. The average age of menarche, based on recent data, has
been reduced in developed as well as in developing countries over the last few decades and is
attributed to various conditions, such as metabolic syndrome, eating disorders, gynecological
cancer, and heart stroke diseases [30–33].
Dysfunctional bleeding is characterized by abnormal bleeding without functional impairment.
It is caused by ovarian dysfunction in 10% of the cases in women of reproductive. The inci -
dence is 10–17% among adolescents and is mainly dependent on the immaturity of the hypo-
thalamic-pituitary-ovarian axis. They are not attributable to structural damage of the genital
tract. In addition, they are observed during all the years of reproductive age.
It constitutes an exclusionary diagnosis at the onset of reproductive age and it is anovulatory
almost in all cases (80–90%). The reason of the bleeding concludes the lack of cyclic secretion
of progesterone resulting in continuous stimulation and endometrial hyperplasia of endog -
enous estradiol. Throughout of this progress the endometrium is overpowered, its perfusion
capacities die resulting in necrosis, while in other places it continues to be repaired [34].
They are usually characterized as anovulatory cycles, even they can also be appeared in nor -
mal cycles as well as they are almost the half of the total metrorrhagia cases.
In some cases, asymptomatic structural abnormalities also coexist, such as polyps and subse-
rous or intramural fibroids. They usually do not affect the whole of the endometrium and are
often of high intensity without excluding the possibility of remaining drooping for several
days. They are generally irregular with fluctuations in their intensity. It is quite often the first
clinical manifestation of systemic hematological diseases especially in adolescents. The disor-
ders are limited just to one of the three phases of the hemostatic procedure. In thrombocyto -
penia and von Willebrand’s disease, there is insufficient platelet clot formation (1st phase of
hemostasis) resulting in metrorrhagia [9]. Menorrhagia may occur in the rare case of VIII, XIII,
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and fibrinogen deficiency (2nd phase of hemostasis), mutation of the M.T.H.F.R. (C677T) gene
(LAME). In these cases, there is a lack of primary platelet clot and fibrin production. Finally,
fibrinolysis (3rd phase of hemostasis) in endometrium can be also observed, especially in
cases of unexplained or intense menorrhagia [9].
4. Anovulatory cycles
Female genital hormone equilibrium disorders observed either in cases of hyperestrogenism
(estrogen escape bleeding) or in cases of sudden subestrogenism (interruption of exogenous
administration – bilateral ovariectomy), or, finally, in cases of progesteronism (progester -
one bleeding bleeding-progesterone withdrawal contraceptive). Diagnosis is often raised
by exclusions (malignant diseases, genital tract, PCO, and hypothyroidism liver cirrhosis).
The mechanisms involved in the pathophysiology of the above-mentioned bleeding cases
are systemic in their nature, although it is possible to observe inadequacy of local hemo -
static mechanisms resulting from the absence of cyclic production of progesterone and related
endothelin-1, prostaglandins and other substances that contribute positively to local hemo -
stasis of the endometrium [ 9]. Additionally, lack of ovulation causes unexpected bleeding,
which adversely affects the quality of life of the patient. Functional hypothalamic or pituitary
disorders that cause suppression of gonadotropin production, anovulation, and the approach
to perimenopausal age cause typical changes in the genital cycle.
Progressively shorter cycles due to a gradual decrease in follicles and a corresponding fall in
ovarian function lead to metrorrhagia [9].
5. Insufficient follicular maturation
Increased FSH levels are associated with abnormal menstrual in duration and time. Impact
on adolescents is including 20–55% of the cycles in the first year and one-third of the cycles in
the third year after menstruation which are still anovulatory. Anabolism is the most common
cause of dysfunctional hemorrhages in adolescence and indeed it can even lead to hospital
care [35]. This is due to functional immaturity of the hypothalamic-pituitary-ovarian axis.
Adolescents whose menstruation appears before the 12th year of age have in 50% anovula -
tory cycles during the first year, while those who are menopausal at the age of 12–13 years
it is needed to pass a period of up to 3 years to make ovulation cycles. Hemorrhage due
to hyperestrogenic cycles are usually characterized by histologically persistent produc -
tive endometrium and hyperplasia caused by progesterone prolonged and progesterone
deficient estrogen mitotic activity [ 9]. The morphological changes in the endometrium are
similar to those observed in women receiving estrogen replacement therapy. The origin of
bleeding can be sought in the apoptosis of the layer accompanied by red blood cell extrava -
sation, the formation of platelet thrombi and fibrin clots in the capillaries, and the existence
of processes related to the reconstitution, including layer formation and hypertrophy of the
regenerated epithelium. Morphological lesions are typically focal and located near or on the
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surface of the endometrium. In contrast, in cases of interruption of the E2/P relationship,
they are diffuse. The exact mechanism of tissue apoptosis in hyperestrogenic endometrium
is unclear. The abnormal development of the endometrium includes additional qualitative
and quantitative changes in microvascularization such as spiral arterial compression and
venous growth, which are often stretched, thus forming abnormal venous networks. Of par -
ticular interest is the fact that the process of neovascularization is inadequate in or near
the hemorrhage focal area while adjacent intact endometrium does not show an increase
in microvascularization. The abnormal morphology of microvascularization accompanies
or is the cause of endometrial hemostasis disorders. Because of the lack of the arachidonic
acid precursor, prostaglandin production is inadequate. Prostaglandins cause more dilation
than contraction, and angiotensin-2 production is reduced. All of the above leads to the con -
clusion that bleeding, in these cases, is caused by vascular density disorders accompanied
by structural abnormalities leading to rupture or degradation of the microvascular system.
This process is followed by the release of lysosomal proteolytic enzymes from the epithe -
lial and stromal cells and from endometrial migrating leukocytes and macrophages, while
granulocytes and activated NK cells secrete perforins. In addition, the ability of contraction
of basal and myometrial vessels is inadequate or absent. All of the above changes contribute
to the inadequate structure and layout and ultimately to the degradation of the capillary
network and constitute the major agents of extensive hemorrhage. Based on the above, the
best therapeutic results are obtained when the bleeding hypertrophic-hyperplastic endo -
metrium is excluded by performing suction biopsy or scraping. In these cases, an extensive
stripping of the base layer is created followed by vasoconstriction of the arteries and arte -
rioles as well as by tissue reconstruction. Functional hemorrhage due to progesteronism
manifests as escape bleeding in women taking progestogens or using contraceptive tablets.
The intensity, duration, and other features of these cases’ bleeding depend on: type, dose
and duration of progestogen administration, the estrogen-progestogen relationship, endog -
enous estradiol levels and the particular endometrial response to hormonal administration
[7, 9]. Endometrial histology in these cases is predominantly influenced by progesterone and
ranges between atrophy with or without cortical conversion of the layer and mixed appear -
ance of productive and secretory elements. The greater the dose and the duration of admin -
istration, the more pronounced is the secretory type atrophy with a pronounced pro-stratum
gland-layer relationship. In this case there is a corrugated endometrial layer especially in the
initial periods of use containing migratory lymphocytes and macrophages as well as granu -
lar endometrial cells. All of the above lesions are associated with abnormalities of endome -
trial angiogenesis. These changes are accompanied by structural lesions and vasodilation
leading to bleeding during the first months of use. The increased concentration of migratory
leukocytes and other cells associated with immunity and the imbalance between metallo -
proteinases (proteolytic MMP enzymes that cause an intrauterine extracellular matrix) and
their inhibitors against them, cause even greater vasodilation [ 7, 9]. In conclusion, the devel-
opment of an abnormal and fragile network of microvascular surfaces in combination with
the release of proteolytic enzymes and poor vasoconstriction due to reduced production of
vasoconstrictors as a result of increased degradation by endopeptidase is the key factor in
the manifestation of the above functional bleeding. Fortunately, the continuation of contra -
ceptives decreases the frequency with the end result being usually observed only during the
first 6–12 months of use.
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6. Ovulatory cycles
They are related to disorders or inadequacy of local hemostasis mechanisms and decreased
spiral arteriolar density. Endometrial histology varies from productive and secretory to
menstrual, and the changes are not different from the corresponding premenstrual women
with normal cycles. There is an increased blood flow to the endometrium whereas the lev -
els of circulating ovarian steroids are normal. The endometrial prostaglandin production
is increased with a priority to vasodilator PGF2a and angiopathic PGE2 types. Prolonged
vasodilation leads to decreased platelet aggregation and increased overexpression of
potential parathyroid-related vasodilatory protein. High proteolytic activity of lysosomal
enzymes in the endometrium as well as fibrinolysis through increased local secretion of
agents with heparin analog activity. The mechanism that triggers all these disorders is pres -
ent unknown [ 9, 35].
6.1. Diagnostic approach
History, gynecological examination, laboratory test such as blood generation, coagulation factors,
βhCG, ultrasound through genital organs, parthenoscopy, magnetic resonance, and laparoscopy.
6.2. Treatment
Adolescent medium degree functional disorders of uterus: Hb > 9gr cyclic providing of
progesterones, contraceptive pills, and iron preparations. In cases of Hb < 9gr, intravenous
hydration, blood transfusion, high dosage of contraceptive pills per os, potential intravenous
providing available estrogens continuing usage of contraceptive pills, and iron preparations.
Activity of the estrogen-progesterinoides agents in haemostasis led to: increasing of TXA2,
platelet agglutination, prothrombin, Factors VIII and X, r eduction of fibronolysis, PGI 2 in
endometrium.
7. Adolescent functional disorders of uterus
Metrorrhagia is a symptom, not a specific disease entity. The effectiveness of treatment is
based on proper diagnosis. It is very important to establish the stabilization of ovulation
cycles. Therapeutic intervention always takes seriously the young of the age [36, 37].
8. Dysmenorrhea
It is a Greek word that has prevailed in the international bibliography as painful menstrual
bleeding 2–3 years after menstruation with onset of ovulation. Frequent disturbance of ado-
lescence ED has primary—no organic damage to the pelvis and secondary—painful ER due to
pelvic conditions such as endometriosis, pelvic inflammation, and congenital abnormalities
of the genital system [38, 39].
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9. Explanatory theories
Theory of Hippocrates: Cervical lumen stenosis and the induced posture of stomach blood are
responsible for the occurrence of dysmenorrhea. Myometric factor: increased myometrial activ-
ity and increased endometrial pressure. Neuromic factors: changing neuromuscular activity
in the uterus after pregnancy may explain the reduction in menstruation pain after childbirth.
• Hormonal effect: women with anorexic cycles do not show painful menstruation.
• Prostaglandins: high levels of PGs are currently the most accepted causal theory
Increased levels of PGF2a and PGE2 and increased PGF2a/PGE2 ratio are observed in ado -
lescents with PD. Also increased levels of LTC4, LTD4, and LTE4 angiotensins, stimulation
of myometrial contractility, and increase in plasma hormone concentrations in women with
dysmenorrhea [38, 39].
9.1. Psychological factors
Subjectivity and fluctuation of the pain, dysmenorrhoea very often presented in family
history.
9.2. Clinical features of dysmenorrhea
Subabdominal pain, nausea, vomiting, diarrhea, irritability, headache, flatulence payment of
forces, depression, and inability to concentrate are clinical features of dysmenorrhea.
9.3. Treatment of dysmenorrhea
PGs synthetase inhibitors, non-steroidal anti-inflammatory agents act by lowering levels of PGs
by reducing levels of PGs, tolfenamic acid, naproxen, and mefenamic acid. The release of PGs
into the menstruation blood is maximal in the first 48–72 hours of EGFR. Contraceptive pills
reduce the amount of menstruation blood, through the controlled increase of the thickness of
endometrial tissue. By inhibiting of ovulation, an endocrine environment with low levels of
PGs is maintained.
Other therapeutic proposals are spasmolytics, analgesics, calcium inhibitors, progesterone,
magnesium, GnRH analogues, leukotriene antagonists, cervical curettage, acupuncture, elec-
tricity stimulation, and psychotherapeutic methods [39, 40].
9.4. Pelvic pain
Primary care of the gynecologist specialized in child and adolescent gynecology is the inves-
tigation of women with chronic pelvic pain. The rate of disease varies among teenagers
between rarity and 19–47% [ 41, 42]. Typical forms of chronic pelvic pain are relatively com -
mon and non-recognition may underestimate their incidence. Mostly have primary second -
ary dyspnea and dysmenorrheal. In girls, the gynecological examination is not feasible and
the rectal examination provides little information. The ultrasound provides information on a
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possible chocolate cyst, hematosalpinx, and free fluid in the Douglas space. In non-response
to NSAID medication, MRI and laparoscopic approaches are recommended with a detection
rate in the specific cases of endometriosis approaching approximately 50%. Endometriosis
symptoms in this age group are not specific, not related to adults, but gives continuous pain
and a normal menstrual cycle. Atypical forms of endometriosis are more common in teenag -
ers and their non-recognition may underestimate their frequency [43–45].
Primary care is the detection of adolescents with chronic pelvic pain experienced by endometriosis
or other pathology. Irritable bowel syndrome is a common bowel dysfunction without attributing
to specific etiology. It is characterized by recurrent chronic abdominal and pelvic pain combined
with bowel dysfunction either as diarrhea or constipation. It is found in 50–80% of women with
chronic pelvic pain and diagnostic criteria are proposed for diagnosis criteria against Rome ii.
Another cause of pelvic pain is congenital abnormalities of the genital system. Clinical symp-
toms are amenorrhea, metrorrhagia, dysmenorrhea, endometriosis, repetitive abortions, in
cases of pregnancy, abnormal position and presentation of fetus, and premature birth [43–45].
Treatment of abdominal pain is a challenge for the specialized gynecologist especially when
an exact diagnosis has not been made. Particularly in these young people, there is a major
harmonic relationship between a young doctor and his/her parents in order to find an organic
cause of the reported symptomatology or in cases where there is no finding of a treatment
analogous to the subjective cause [43, 44].
10. Contraceptive methods
The purpose of contraception is to prevent fertilization of the ovum from the sperm or to prevent
implantation of the fertilized egg in the uterus. There are many methods of contraception for every-
one to be educated. The ideal method of contraception attaches to the prevention of an unwanted
pregnancy but also protects against sexually transmitted diseases. Of approximately, 3 million
unwanted pregnancies that occur in the United States, 54% of these do not use contraception.
10.1. Contraceptive methods
Natural methods: withdrawal method (coitus interruptus) of approximately 57% is used in
adolescent women with a failure rate of about 22% and lack of protection against sexually
transmitted diseases.
1. Reversible (small time action) [46–49].
• Men’s condoms
• Hormonal methods (contraceptive tablets, vaginal ring, transdermal patches)
• Other methods (contraceptive diaphragm, cervical cap)
2. Reversible (long time action) [46–49].
• Intrauterine device
• Implants
Family Planning196
3. Irreversible
• Tubal ligation
• Seminal duct ligation
4. Emergency contraception
• Levonorgestrel
• Ulipristal acetate [46–49].
11. Contraceptive pills
It is a complex issue that causes family embarrassment to healthcare professionals in govern-
ment officials in civil servants and young people themselves. There has been extensive effort
to increase the use of contraceptive methods and in particular the condom to avoid pregnan-
cies and sexual transmitted diseases.
Definitely it is necessary to set up Family Planning Centers for Teenagers, which must become a
priority for each government. Basic award principle for contraceptive pills, as long as necessary, as
little as possible [50]. Contraceptive capacity of contraceptive pills is estimated by the Pearl Index
(Pearl Index). All formulations with combined oral hormonal contraception have Pearl index ≤1.25
women (years). There are several differences regarding the hormonal components contained in
each formulation which may vary depending on the type, composition, quantity, and number
of active tablets. Single-phase formulations contain active tablets with the same constant amount
of estrogen and progestogen ratio. In contrast, the above ratio changed in the multiphase pills.
Biphasic have two different combinations, the three phase and recently there are also four phases
with successive decrease in the estrogen ratio and corresponding increase in the progestogen ratio.
Contraceptive pills have not been associated with weight gain and mood changes. It is recom-
mended to take single-phase pills in teenagers for their menstrual bleeding disorders [51–55].
Contraindications of contraceptive pills are BP ≥160/100 mmHg, liver disease, migraines with
focal neurological symptoms, diabetes, nephropathy, neuropathy, retinopathy, or angiopathy
complications are also included.
History of thromboembolism (particularly with third generation pills with drospirenone),
thrombophilia, factor V Leiden mutation, factor II mutation (G20210A allele), antiphospho -
lipid antibodies, protein C deficiency, protein S deficiency, antithrombin III deficiency, undiag-
nosed vaginal bleeding, and estrogen-dependent breast cancer compromise contraindications
for contraceptive pills. Smoking is a relative contraindication for the use. According to FDA
(April 2012), revision of contraceptive pills guidelines with drospirenone increases three times
the risk of thrombosis compared to other progestogens. Clots are caused by contained estrogen.
11.1. Impact of thrombophilia
• Total population: 1 per 10,000 woman years per year.
• Contraceptive pills: 4 per 10,000 woman years per year.
• Pregnancy: 10–20 per 10,000 woman years per year [56].
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11.2. Positive actions
Circulation disorders such as hypermenorrhea, hypomenorrhea, metrorrhagia restoring a
normal menstrual cycle, and prolong the menstrual cycle. Dysmenorrhea decreases through
the action of prostaglandin synthesis. They also improve the presence of premenstrual syn -
drome, premenstrual edema, irritability, anxiety, and depression.
Ovary cancer risk is decreased by about 20% per 5 years of use and 50% for 15 years.
There is no protective action for mucosal ovarian cancer. They decrease the risk of endome -
trium cancer by 50% every 4 years of use and 70% after 12 years. Cancer of cervix represents
an independent factor with a relative risk probably due to co-factors (HPV, intercourse with-
out condoms). According to the WHO, there is a slight increase in the relative risk for users
of contraceptive pills over a period of >4 years. Higher relative risk is increased for users over
10 years. The above may be affected by the use of non-barrier methods by the number of sex
partners by multiparity and alcohol consumption.
It is believed that hormonal contraception, especially estrogen as mitotic agents, enhances neo-
plastic process particularly in women with HPV infection. Estrogenic probably affects specific
DNA sequences.
Additionally, there is a direct interaction between estrogen receptors and HPV E6 and E7
protein. The problem of the possible relationship between breast cancer and hormone therapy
is still largely unresolved.
The results that are available now suggest that relatively short-term treatment (less than
5 years) does not increase the risk.
For a treatment with longer duration, the existing results based primarily on estrogen mono-
therapy do not allow clear conclusions without excluding the possibility that the frequency
could increase under these conditions. It is difficult to evaluate the role of progestogen added
to the above treatment. So, it is preferable to utilize steroid hormones with anti-mitotic activ-
ity. It is known that hydroxyprogesterone derivatives such as medroxyprogesterone acetate
can inhibit tumor growth activities.
There are indications that use of contraceptive pills over a period of 10 years can cause a mod-
erate increase of the relative risk (24%) to the oncogenic progression for breast cancer . With
discontinuation, this risk decreases to 0% in 10 years. It is also gained ground the aspect that
this risk is greater in women with a family history, with the risk of being limited to second
degree relatives. It is unlikely, however, to incriminate only estrogen because of the fact that
there are minimal estrogen receptors in normal breast epithelial cells.
The progesterone may promote the mitotic process and cause atypia. It is known that the
mitotic action on MCF-7 cells of human breast cancer of 19 nor-progestogen (norethindrone,
gestodene, and 3-ketodesogestrel) [56–60].
In conclusion, progestogen should be emphasized that any attempt to adapt to the clinical
practice of the experimental anti-mitotic action of a pregestogen should be done very care -
fully. Only well-tested prospective clinical trials may answer the question whether the protec-
tive effect found in the laboratory has the potential clinical application.
Family Planning198
Contraceptive pills advantages include ovarian cysts treatment, endometriosis, dysmenor -
rhea, dyspareunia, metrorrhagia, acne and decreased androgen synthesis, hirsutismus, spe -
cific activity of estrogen and antiandrogens, mastodynia, symptom reduction mastopathy,
reduction of benign mastopathy, and bone increase density [60, 61].
What do women think about birth control pills from our own child and adolescent gynecol -
ogy center housed in the Democritus University Family Planning Laboratory. Positive effects:
positive effect on sexual life, reliability, easy to use/comfort, less bleeding, regulation of men-
struation, and less painful periods.
Negative effects: nausea, headaches, changes in mood, feeling of tension on the breasts, and
increase of weight.
11.3. Action mechanism of contraceptive pills
• Suspension of implantation
• Ovulation inhibition
• Thickening of cervical mucus
• Sperm motility disorder [62, 63].
Oral contraceptive pills (OCPs) perform their action through a variety of mechanisms, through
the inhibition of the mesocyclic peak of gonadotropin secretion resulting in the suppression
of ovulation.
Contraceptive action is mainly exercised through the progesterone of OCPs, which cause ovu-
lation suppression by multiple mechanisms:
• ↓ Luteinizing hormone (LH).
• The thickening of the cervical mucus and ↓ of the sperm penetration.
• ↓ of fertilization capacity of the semen, the disturbance of normal motility and occlusion of
the fallopian tubes.
• Obstruction of implantation due to endometrial perforation [62, 63].
Estrogens exert their contraceptive action, but they are dose-dependent, by inhibiting the
secretion of gonadotropins (FSH and LH), cause the uterus to change its secretory capacity of
the cellular structure of the endometrium.
There are several differences regarding the hormonal components contained in each formu -
lation which may vary depending on the type, composition, quantity, and number of active
tablets. Single-phase formulations contain active tablets with the same constant amount and
estrogen and progestogen ratios. In contrast to multiphase, the above ratio changes of bipha-
sic have two different combinations, the three phase have three and recently, there are also
four phases with successive reductions in the estrogen ratio and a corresponding increase in
the progesterone ratio [62, 63].
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With regard to the first few generations because the dosage did not decrease at the appro -
priate time, side effects such as unwanted bleeding or spotting often occurred. The second
generation was more effective and longer half-life, but with increased androgenic action that
helped to sexual desire, however, it could lead to hypertrichosis, acne, and dyslipidemia. The
third generation retains the effectiveness of the progestogen while reducing its androgenic
effect. Smaller androgenic effect also makes estrogen more effective. This however entails a
greater risk for thromboembolic events [62, 63].
11.4. 4th generation contraceptive pills
The widespread use of a combination of estrogen and progesterone as a contraceptive or
hormone replacement therapy has made it possible to complete large epidemiological studies
that have made it possible to assess the benefits and risks that may have arisen.
Among the major advantages of use, are included primarily the reduced incidence of endo -
metrium cancer, attributed mainly to the antimitotic progesterone activity, and secondly, the
reduced frequency of ovaries cancer, due anti-gonadotropic action combination [62, 63].
11.5. Contraceptive vaginal ring
It releases daily and for 21 days 120 μg of etonogestrel and 15 μg of ethinylestradiol (nesto -
rone ring study 15–20 μg EU + 150–200 μg nestorone).
It remains in place for 3 weeks and the fourth week it is removed for bleeding to escape. It is
possible to be removed during sexual intercourse.
Existing progesterone: etonogestrel (3-keto desogestrel) 19-nortestosterone derivative.
Nestorone belongs to the norprogesterone family and is weakly active by oral administration. It
does not bind significantly neither to the androgen receptor, nor to the estrogen receptor. It is a
flexible, transparent silicone ring. It secrets daily 15 μg ethinylestradiol and 120 μg etonogestrel.
Its diameter is 53 mm with cross section 4 mm. The duration of usage is 1 month, 3 weeks/1 week.
It is direct start fitting and has possibility to maintain up to 35 days. The next placement can
be without delay. There is less interruption for a shorter duration of menstruation. Tampons,
spermicide nonoxynol-9, or intravaginal miconazole should not to be used at the same time.
It can be removed in less than 3 hours. It does not affect in sexual contact.
It causes breast tenderness, headaches and nausea, spotting, vaginal intolerance or hyperse -
cretion, and unconceivable loss or misuse. There are no studies evaluating its effect on ado -
lescent bones. There is no evidence of VTE in relation to low-dose OCPs. Ease of use has not
demonstrated increased compliance or prolonged use (<30% in 6 months) [64, 65].
11.6. Evra patch contraceptives
They release EE 600 μg with norelgestromin 6 mg. They remain placed for 7 days for 3 consecu-
tive weeks followed by 1 week without patch. It is a useful alternative method for women who
hardly remember daily taking the pill because if they forget there is a 2 day error margin. It
should be avoided when weight greater than 90 kg. The increased exposure to estrogen compared
to oral contraceptive pills creates 1.6 and 1.2–2.2 higher probability of deep thrombosis [65, 66].
Family Planning200
11.7. Implants
They modify cervical mucus (viscosity in reduced amount) prevent sperm penetration and
suppress endometrial growth which becomes inappropriate for implantation.
It is an ideal contraceptive method for teenagers who do not want to deal with contraception
often [65].
11.8. Injectable contraceptive preparations
Injectable contraceptive preparations medroxyprogesterone acetate depot, intramuscular
protection 3 months with efficacy 99.7%.
Monthly combined contraceptives estradiol cypionate and medroxy progesterone acetate
depot, valerian estradiol, and norethrone acetate.
They improve dysmenorrhea increase the risk of thromboembolic events and may cause men-
strual disorders [65].
11.9. Transdermal contraceptive patches evra
Transdermal contraceptive patches evra release ethinyl estradiol 600 μg with norelgestro -
min 6 mg. They remain placed for 7 days for 3 consecutive weeks followed by 1 week with -
out patch it is a useful alternative for women who hardly remember daily taking the tablet
because if they forget there is a 2 day error margin. They should be avoided when weight of
the woman is greater than 90 kg. There is an increased exposure to estrogen compared to oral
contraceptive pills 1.6 and 1.2–2.2 with higher probability of deep vein thrombosis [65, 66].
11.10. Subdermal implants
They modify cervical mucus (viscosity in a reduced amount), prevent sperm penetration, and
suppress endometrial growth which becomes inappropriate for implantation. It is an ideal
contraceptive method for teenagers who do not want to deal with contraception often [65].
11.11. Injectable progestogens
Injectable progestogens contain depot medroxyprogesterone acetate, intramuscular site of
injection and they offer protection for 3 months with efficacy 99.7%.
Combined oral contraceptive pills estradiol cypionate and depot medroxyprogesterone acetate,
valerian estradiol, and norethrone acetate.
They improve dysmenorrhea, increase the risk of thromboembolic events, and may cause
menstrual disorders [67].
11.11.1. Barrier methods
• Male condoms.
• Female condoms.
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• Sponge.
• Diaphragm.
• Birth control rings.
• Spermicides.
From contraceptive barrier methods, the most widespread, economic, easy to use, well
accepted by both partners, with the greatest contraceptive success and the greatest protection
against sexually transmitted diseases is the male condom, 75% of adolescents report using a
condom with a failure rate of 18% [68].
11.12. Intrauterine contraception
Copper intrauterine device is the most effective reversible method of contraception in terms
of cost-effectiveness which is the first method of contraception with a coil used in the world.
Mirena, which was released in 1997, is a type of intrauterine device with levonorgestrel that
contains 52 mg levonorgestrel and yields 20 μg/24 h for 5 years.
They can cause amenorrhea or oligomenorrhea.
11.13. Innovations
Forming new IUD with less levonorgestrel that will be easily applied to nulliparous women
(Femilis and Femilis slim) are under construction and they are another IUD without side
arms, for easy adjustment to various sizes of uterus IUD (SPRM) (ulipristol).
Aims of intrauterine devices:
• Contraception.
• Menorrhagia.
• Endometrial protection.
11.14. Side effects
The use of IUD can cause tempοrarily edema, headache, tenderness, depression and breast
tenderness, acne or other skin lesions. There are may also be appeared: abdominal pain in
the lower part of the abdomen, vaginal discharge, nausea, functional ovarian cysts and rarely
spotting, especially in the first months [69].
11.15. Mirena
Mirena is an intrauterine device effective in relation to the main indication of its usage which
is contraception. It could be also used as a reliable therapeutic method of menorrhagia. In
many cases, reduce dysmenorrhea. It reduces the risk of pelvic inflammatory disease and
ectopic pregnancies.
Family Planning202
Finally, it protects woman in perimenopausal and postmenopausal periods who are under
hormonal replacement therapy with estrogens from endometrial hyperplasia indicated in
puerperium.
Contraindications conclude pelvic inflammatory disease. HIV and immunosuppressant are
not contraindications. Risk of expulsion in women of reproductive age is 3–5% and in ado -
lescents 5–22%.
12. Conclusion
From the above mentioned, we conclude that with the preventative gynecological control in
females of young age, a prompt diagnosis and appropriate treatment, in particular congenital
abnormalities of the genitals and investigation of clinical symptoms of these individuals, can
be made.
Early diagnosis and treatment of ovarian tumors despite their small incidence of genital can-
cers up to 18 years of age is of major clinical importance because they are not always accom -
panied by a characteristic clinical picture.
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