Puberty is a period of physical and psycho-emotional maturation, which is characterized by the formation of the typical secondary sexual characteristics under the action of the produced sex hormones. Physiologically, girls enter puberty earlier than boys, and the average age of onset of puberty for them is 10 ± 2 years. Various disorders can lead to an earlier or later onset of puberty. With the onset of puberty in girls, the secretion of hormones along the hypothalamus-pituitary-gonadal axis is activated. As a result of this activation, gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus, which stimulates the production of gonadotropins from the pituitary gland – follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Breast glands (telarche), pubic hair (pubarche), and first menstruation (menarche) develop sequentially. The term late puberty in girls refers to the absence of secondary sexual characteristics after the age of 13. There is hypogonadism, which can be subdivided into hypogonadotropic and hypergonadotropic. In hypogonadotropic hypogonadism, there is a reduced production of gonadotropins from the pituitary gland, while in hypergonadotropic hypogonadism, secretion of gonadotropins is normal, but there is no response to their action from the gonads. The normal age for first menstruation in Bulgarian girls is 12.7 ± 1.2 years. Primary amenorrhea is the absence of menstruation in girls aged 16 years who have developed secondary genitalia or in girls aged 14 years who have not developed secondary genitalia. What are the most common causes of late puberty and primary amenorrhea? The causes can be divided into 3 groups: 1. Disorders due to hypogonadotropic hypogonadism – reduced or inhibited production of gonadotropin-releasing hormone, which leads to reduced secretion of FSH and LH and subsequent anovulation (so-called hypothalamic amenorrhea) or mutations in the receptors for GnRH, leading to the so-called pituitary amenorrhea. Among the conditions that manifest with hypogonadotropic hypogonadism are: Tumors in the area of ​​the hypothalamus and pituitary gland – the most common such tumor is prolactinoma; Kallman’s syndrome – a combination of lack of smell (anosmia) and deficiency of FSH and LH; Congenital isolated deficiencies of luteinizing and follicle-stimulating hormones; Hypopituitarism – reduced function of the parathyroid glands; Congenital adrenal insufficiency – a defect in the enzyme 21-hydroxylase, which leads to the accumulation of 17-hydroxyprogesterone; 2. Disorders due to hypergonadotropic hypogonadism – the most common cause is ovarian dysgynesia as a result of Turner’s syndrome. Turner syndrome is a congenital genetic disorder in which one X chromosome is missing. 3. Structural abnormalities leading to late puberty and primary amenorrhea: Uterine hypo- and aplasia, cervical atresia (lack of opening), vaginal agenesis (so-called Mayer-Rokitansky-Kuster-Hauser syndrome),due to complete or partial agenesis of the Müller ducts – patients with this syndrome have a normal karyotype combined with uterine aplasia and aplasia of the upper two-thirds of the vagina; Asherman’s syndrome – acquired as a result of traumatic damage to the uterine mucosa, a condition in which a healing mechanism is triggered with the formation of connective tissue in the uterine cavity. As a result of these adhesions, the volume of the uterine cavity decreases, which creates problems with pregnancy and wear of the fetus. Diagnosing and determining the etiological factor leading to primary amenorrhea and late puberty is a complex and long process. A complete hormonal examination, head imaging to rule out tumor formations, ultrasound examination of a small pelvis, hysterosalpingography, karyotyping are needed. The treatment of primary amenorrhea depends on the cause leading to its appearance. In most cases, hormone therapy is required. In the presence of hyperprolactinemia as a result of prolactinoma, the treatment is with dopamine agonists. In some cases, therapy with gonadotropins or GnRH may be necessary.