Treatment of delayed puberty

The goals of treatment of delayed puberty

• Prevention of malignancy of dysgenetic gonads located in the abdominal cavity.
• Stimulation of pubertal growth growth in patients with growth retardation.
• Replenishment of the deficiency of female sex hormones.
• Stimulation and maintenance of the development of secondary sexual characteristics for the formation of a female figure.
• Activation of the processes of osteosynthesis.
• Prevention of possible acute and chronic psychological and social problems.
• Prevention of infertility and preparation for procreation through extracorporeal fertilization of the donor egg and embryo transfer.

Indications for hospitalization

Carrying out of medical-diagnostic actions:

• samples with analogues of the releasing hormone;
• study of circadian rhythm and night secretion of gonadotropins and growth hormone;
• samples with insulin and clonidine (clonidine) to clarify the reserves of soma-thotropic secretion.

The determination of the Y chromosome in a karyotype in a woman with a female phenotype is an absolute indication for bilateral removal of the sexual glands in order to prevent their tumor degeneration.

Non-drug treatment of delayed puberty

For girls with central and constitutional forms of delayed puberty - adherence to the work and rest regime, correction of physical activity, maintenance of adequate nutrition and compensation of the basic somatic disease.

Medication for delayed puberty

There are no reliable data on the effectiveness of vitamin-mineral complexes and adaptogens in girls with a constitutional delay in puberty. After a test with DiPr, the activation of puberty in such children was noted. Girls with a constitutional delay in puberty can carry out 3-4-month courses of treatment with drugs containing sex hormones in a constant sequential regime and used for hormone replacement therapy.

As a non-hormonal therapy, patients with hypogonadotropic amenorrhea are recommended a complex consisting of individually selected antihomotoxic drugs or drugs that improve the function of the central nervous system. The course of treatment should be at least 6 months. The choice of further tactics should be based on the dynamics of the content of gonadotropic hormones, estradiol, testosterone and data on monitoring the size of the uterus and the condition of the ovarian follicular apparatus.

Patients with a hypergonadotropic form of delayed puberty against the background of gonadal dysgenesis for the purpose of initial estrogenization of the body are shown daily therapy with estrogens in gel (divinyl, estrogen, etc.), tableted (1-2 mg / day, 2 mg / day, 2 mg / day etc.) form or in the form of a patch (a clitoris, an estroder, etc.) or conjugated estrogens in tablets daily (premarin in a dose of 0.625 mg / day, etc.). The use of ethinyl estradiol in tablets daily (microfillin at 25 μg / day) is currently limited due to the possibility of unfavorable or inadequate development of the mammary glands and uterus. Because of the high risk of malignant degeneration of the sexual glands on the background of taking estrogenic drugs, hormone replacement therapy for patients with 46.XY karyotype and gonadal dysgenesis should be performed strictly after bilateral gonad and tubectomy.

When regular menstrual reactions appear, the cyclic regimens include dystastine, dydrogesterone, 10-20 mg / day, utrozhestan (progesterone) at a dose of 100-200 mg / day, or medroxyprogesterone acetate, 2.5-10 mg / day from the 19th to the 28th day of taking estradiol). It is possible to administer estradiol as a sequential combination with progestogens (divin, klimonorm, cycloproginov, klimen) in a 21-day regimen with interruptions of 7 days, and in a constant mode without interruptions (femostone 2/10). In patients older than 16 years for the rapid emergence of secondary sexual characteristics and the increase in the uterus, it is advisable to apply divvren. To accelerate the formation of mammary glands, the appointment of combined oral contraceptives is recommended. After achieving the desired results in both cases, the transition to the drugs used in the constant sequential (sequential) regimen is shown.

In addition to hormone replacement therapy, when detecting a decrease in bone mineral density, osteogenone is prescribed 1 tablet 3 times a day for 4-6 months per year. The drug is taken under the control of bone age until the closure of growth zones and under the control of densitometry of XY-gonadal dysgenesis. It is advisable to conduct 6-month courses of therapy with calcium preparations: napekel D ₃, calcium D-Nycomed, Vitrum Osteomag, calcium-Sandoz forte.

In stunted patients with hypo- and hypergonadotropic gonadism with growth rates below 5 percentiles, somatropin (recombinant growth hormone) is used. The drug is administered subcutaneously daily once a night. The daily dose is 0.07-0.1 IU / kg or 2-3 IU / m ², which corresponds to a weekly dose of 0.5-0.7 IU / kg or 14-20 IU / m ². As the girl grows, the dose needs to be changed regularly taking into account the mass or surface area of the body. The therapy is carried out under the control of growth every 3-6 months until the period corresponding to bone age 14 years, or with a decrease in the growth rate to 2 cm per year or less. Girls with Turner syndrome require a large initial dose of the drug. The most effective use of 0.375 IU / kg per day, but the dose can be increased.

For stunted girls with Turner's syndrome, in order to increase growth, one can prescribe oxandrolone (a non-aromatizing anabolic steroid) at a dose of 0.05 mg / kg daily for 3-6 months with the use of growth hormone.

When choosing the type of therapy with sex steroids, aimed at replenishing the estrogen deficiency, and the dose of drugs should be guided not by the chronological (passport), but by the biological age of the child. Currently, it is customary to use preparations similar to natural estrogens, according to the growing pattern, if the bone age has reached 12 years.

The initial dose of estrogen should be 1 / 4-1 / 8 of the dose used to treat adult women: estradiol in the form of a patch at 0.975 mg / week or as a gel at 0.25 mg / day or conjugated estrogens at 0.3 mg / day course for 3-6 months. In the absence of menstrual-like bleeding during the first 6 months of taking estrogens, the initial dose of the drug is increased 2-fold and after at least 2 weeks, progesterone is additionally prescribed for 10-12 days. When bleeding occurs, you should proceed to the modeling of the menstrual cycle. Assign estradiol in the form of a patch to 0.1 mg / week or gel at 0.5 mg / day or conjugated estrogens at a dose of 0.625 mg / day with the addition of preparations containing progesterone (dydrogesterone 10-20 mg / day or micronized progesterone (morning) ) at 200-300 mg / day). Estrogens are taken daily continuously, progesterone - for 10 days after every 20 days of taking estrogens. It is possible to take medications containing an analog of native progesterone every 2 weeks against the background of continuous use of estrogens. During 2-3 years of hormonal treatment, you should gradually increase the dose of estrogen to a standard dose, taking into account the growth rates of body length, bone age, size of the uterus and mammary glands. The standard dose of estrogen to compensate for the deficiency of estrogenic effects, which usually does not have negative consequences, is 1.25 mg / day for conjugated estrogens, 1 mg / day for estradiol-containing gel and 3.9 mg / week for the patch with estrogens. Undoubted comforts have preparations containing estradiol and progesterone (medroxyprogesterone, dydrogesterone) with a fixed ratio. Therapy with higher doses of estrogen leads to an accelerated closure of the epiphyseal growth zones and the development of mastopathy, increases the risk of developing endometrial cancer and mammary glands.

The main criteria for the effectiveness of the therapy being administered are the onset of growth and development of the mammary glands, the appearance of sexual embryo, the increase in linear growth and the progressive differentiation of the skeleton (the approach of biological age to the passport age).

Surgical treatment of delayed puberty

Surgical intervention is indicated for patients with growing cysts and tumors of the pituitary gland, the hypothalamic region and the third ventricle of the brain.

Due to the increased risk of neoplastic transformation of the dysgenetic sexual glands located in the abdominal cavity, as well as the high rate of detection of the pathology of the fallopian tubes and mesosalpinx, all patients with XY gonadal dysgenesis immediately after diagnosis are required to remove the uterine appendages (together with the fallopian tubes) method.

Approximate terms of incapacity for work

From 10 to 30 days during the examination and conducting diagnostic procedures in a hospital. Within 7-10 days during the period of surgical treatment.

Further management

All girls with a constitutional delay in puberty should be included in the risk group for the development of bone mineral density deficiency and need dynamic follow-up until the end of puberty.

Patients with ovarian form of delayed puberty and hypogonadotropic hypogonadism in the absence of the effect of non-hormonal treatment need lifelong replacement therapy with sex steroids (before the period of natural menopause) and in constant dynamic observation. To avoid overdose and undesirable side effects during the first 2 years of treatment, it is advisable to perform a follow-up check every 3 months. This tactic allows you to establish psychological contact with patients and timely adjust the treatment scheme. In subsequent years it is enough to conduct a follow-up examination every 6-12 months. In the process of long-term hormonal treatment, it is advisable to conduct a control examination once a year. The minimal complex of studies should include: ultrasound of genitals, dairy and thyroid glands, colposcopy, as well as determination of blood plasma levels of FSH, estradiol, progesterone, according to indications of TSH and thyroxine in the second phase of the simulated menstrual cycle. The level of estradiol in 50-60 pmol / l is considered to be minimal to ensure the response of target organs. The normal level of estradiol required for the functioning of the main organs of the reproductive system and maintenance of normal metabolism is in the range of 60-180 pmol / l. At least 1 time in 2 years, it is necessary to evaluate the dynamics of bone age when it falls behind the calendar, if possible, the examination of the bone system should be supplemented with densitometry.

Information for Patient

It is advisable to teach patients the skills of using drugs (transdermal dosage forms, injections of growth hormone) and explain the need for strict control of their intake because of the risk of acyclic uterine bleeding when the treatment regimen is violated. If hormone replacement therapy is necessary, patients and their parents should be trained by experienced medical personnel to administer the drug.

Patients should be informed of the need for long-term (up to 45-55 years) hormone replacement therapy to compensate for the deficiency of estrogens affecting not only the uterus and mammary glands, but also the brain, blood vessels, heart, skin, bone tissue, etc. Against the background of hormone replacement therapy, annual monitoring of hormone-dependent organs is necessary. It is advisable to maintain a diary of self-control, indicating the timing of the onset, duration and intensity of menstrual bleeding. Independent pregnancy is impossible. But despite this, with the regular intake of female sex hormones, the uterus can reach the size that allows transplanting the donor egg, fertilized by artificial means.

Breaks in the therapy of patients with hypogonadotropic and hypergonadotropic hypogonadism are not permissible. Termination of hormone replacement therapy or a break in the treatment of more than two cycles causes the development of a deep estrogen deficiency state with the appearance of vegetative reactions and metabolic disorders, hypoplasia of the mammary glands and genital organs.

Forecast

The prognosis of fertility in patients with a constitutional form of delayed puberty is favorable.

With hypogonadotropic hypogonadism and ineffective therapy consisting of individually selected antihomotoxic drugs or drugs that improve the function of the central nervous system, fertility can be temporarily restored by exogenous administration of LH and FSH analogues (with secondary hypogonadism) and GnRH analogs in the cirrchoral regimen (with tertiary hypogonadism).

With hypergonadotropic hypogonadism, only patients can get pregnant on the background of adequate hormone replacement therapy by transferring the donor embryo to the uterine cavity and fully recovering the deficiency of the hormones of the yellow body. Discontinuation of medication, as a rule, leads to a spontaneous abortion. In 2-5% of women with Turner syndrome who had spontaneous puberty and menstruation, pregnancy is possible, but its course is often accompanied by a threat of interruption at various gestational age. The favorable course of pregnancy and childbirth in patients with Turner's syndrome is a rare occurrence and more often at the birth of boys.

In patients with congenital hereditary syndromes accompanied by hypogonadotropic hypogonadism, the prognosis depends on the timeliness and effectiveness of correction of concomitant diseases of organs and systems.

Patients with hypergonadotropic hypogonadism with timely initiated and adequate treatment can realize reproductive function by extracorporeal fertilization of the donor egg and embryo transfer.

Patients who did not receive hormone replacement therapy in the reproductive period, more often than on average in the population, suffer from hypertension, dyslipidemia, obesity, osteoporosis; they often have psychosocial problems. Especially for women with Turner syndrome.

Prevention

Data confirming the existence of the developed measures to prevent the delay of puberty in girls are absent. When central forms of the disease, due to nutritional deficiency or inadequate physical exertion, it is advisable to observe the work and rest regime against the background of rational nutrition before the onset of puberty. In families with constitutional forms of delayed puberty, it is necessary to observe the endocrinologist and gynecologist from childhood. With dysgenesis of gonads and testicles, prevention does not exist.