Treatment of sexual dysfunction

Treatment of the congenital pathology of sexual development consists of several aspects. The main issue is the establishment of the patient's gender, adequate to his biological and functional data, taking into account the prognosis of the possibility of sexual activity.

If the corresponding sex of the underdeveloped genitalia, the absence or surgical removal of the gonads, as well as in case of growth disorders, hormonal correction of development is necessary, forming a phenotype approaching the norm and providing a normal level of sex hormones.

Surgical correction of the floor involves the formation of external genitalia depending on the sex chosen (feminizing or masculinizing reconstruction), as well as addressing the fate of gonads (their removal, removal from the abdominal cavity, or the descent of testicles into the scrotum). When choosing a male patient with dysgenesis of testicles, removal of the rudimentary uterus is not necessary from our point of view, since in the future its presence does not give any complications. Some patients with the syndrome of incomplete masculinization and testicular feminization need to create an artificial vagina.

The choice of sex, as in all cases of hermaphroditism, depends on the degree of masculinization of the external genitalia and the androgen-producing ability of testicles. In connection with a decrease in tissue sensitivity to androgens, substitute androgen therapy does not always give the desired effect. Surgical correction in the male direction is facilitated by the fact that the testicles are most often extra-abdominal, so there is no need for laparotomy. Biopsy of both testicles is necessary not only for oncologic indications, but also for predicting their functional capabilities.

Surgical correction in the female direction is complicated by the functional inferiority of the vagina: in addition to the feminizing plastic of the external genitalia and the removal of testicles, in most cases it is necessary to perform the operation of creating an artificial vagina. The work of recent years has shown the justification of one-stage corrective surgical measures in childhood. Using the method of sigmoidal colpopoiesis, they proved its effectiveness not only from the position of functional possibilities for sexual life in the future, but also the enormous deontological significance of complete early correction.

Tactics in relation to testicles to puberty are unified: if there are no tumor changes, their ventrofixation is performed. In pubertal testicles can exhibit undesirable androgenic activity, causing coarsening of the voice, hirsutism. Then they are removed from under the skin of the abdomen, where they were fixed.

Hormonal correction in the choice of the female direction of development is substitutive, but differs from that with the congenital pathology of sexual development with the stored derivatives of the Müller derivatives. In view of the absence of the uterus, the menstrual function is irreplaceable, so there is no need for cyclic introduction of female sex hormones; they are given constantly, daily for the entire period corresponding to the fertile age. This is the development of female secondary sexual characteristics, complementing surgical rehabilitation.

Hormonal therapy of patients with female civil sex

In case of agenesis or when female testis is selected for testicular forms of hermaphroditism, and testicles must be removed for oncological indications or in order to avoid unwanted androgenization, there is a need for therapy with preparations of female sex hormones. Treatment is a substitute (replenishes the lack of endogenous estrogen). Therefore, from puberty age, treatment continues for the entire period corresponding to the pedigree. The goal of therapy with female sex hormones is to promote the proper formation of the female phenotype, the development of female secondary sexual characteristics and genital organs and to prevent the manifestation of castration syndrome. In patients with no gonads from pubertal age, the content of gonadotropins sharply increases, reflecting the state of overstrain of the hypothalamic-pituitary system. Evidence of the adequacy of substitution therapy with drugs of female sex hormones is a reduction in the level of gonadotropins of blood to normal.

In patients admitted to adulthood, treatment with estrogen is recommended to begin no earlier than the period corresponding to the physiological pubertal, taking into account the growth of the child and the extent of the lag of the bone age from the actual one. With tall and sharp lag in the bone age (which is more often observed with "pure" gonad agenesis and the eunuchoid form of incomplete masculinization syndrome), estrogen therapy has to start already from 11-12 years. This contributes to a more rapid maturation of the skeleton and prevents the development of sub-gigantism and eunuchoid body proportions. With short stature ("turnaround" forms) and a slight lag in the bone age from the actual treatment, it is advisable to start from 14-16 years, so that the closure of the "growth zones" occurs as late as possible.

Since the treatment is carried out for a long time, it is preferable to prescribe oral preparations. Only in those cases when their use is undesirable (poor tolerance, low effectiveness) for some reason, it is necessary to resort to parenteral administration of estrogen preparations of prolonged action (estradiol-dipropionate, estradiol-benzoate, etc.). Usually they tend to imitate the gradual increase in their level in the pubertal period with estrogen therapy. Treatment can be started either immediately by a cyclic (intermittent) scheme, or at first continuously, until the appearance of induced menstruation. We give preference to the continuous type of the onset of estrogen therapy, as menstrual-like bleeding usually appears on this background, which, in our opinion, reflects the own hypothalamic cycles. "Adjusting" to the revealed own cycles, further treatment can be carried out on a cyclic schedule from the 5th to the 26th cycle. Naturally, the emergence of induced menstruation is possible only in patients with preserved Muller derivatives, i.e., with gonadal agenesis and testicular dysgenesis syndrome. In other patients, there is no need to switch to this therapy scheme.

Biorhormonal treatment with estrogens and gestagens is carried out later, when the development of estrogen-dependent target organs (mammary glands, external and internal genitalia) becomes sufficient and natural two-phase cycles are simulated. Considering the psyche of patients who are forced to be treated for many years, the scheme should be simplified as much as possible. The best effect is provided by the substitution therapy with biohormonal estrogen-progestational drugs, widely used in healthy women for the purpose of contraception (infecundin, bisekurin, non-vellon, etc.). Estrogen content in them is sufficient to induce induced menstruation and further development of secondary sexual characteristics. The gestagenic component prevents the pathological manifestations of relative hyperestrogenia (hyperplastic processes in the endometrium and mammary glands).

We observed a good effect from the combination of synthetic estrogens with the administration of a 12.5% solution of oxyprogesterone capronate 1 ml intramuscularly on the 17th day of the induced cycle. We consider categorically contraindicated interruptions in substitution therapy for female sex hormones in patients with gonadal agenesis and after castration: removal of hormone therapy immediately leads to an increase in the gonadotropic activity of the pituitary gland according to the type of post-stroke syndrome and promotes the development of endocrine-exchange and vascular disorders characteristic of it. A high level of gonadotropins can stimulate the occurrence of metastases of gonadal tumors. At the same time, estrogen replacement therapy for gonadal and castration agenesis, in contrast to the use of these hormones with preserved ovaries (for example, as contraceptives or menopausal disorders), does not lead to the risk of developing endometrial cancer or mammary glands, as estrogen drug dosages are not cumulative with endogenous estrogens and do not give a high saturation of the body with these hormones.

With insufficient development of pubic hair, in some cases additional addition of androgens, for example methyltestosterone (5-10 mg per tongue for 3-4 months from the 5th to 26th simulated estrogen preparations of the cycle) is justified. With the preserved sensitivity to androgens during this period, satisfactory sexual hairs develop, although the development of mammary glands may be inhibited. Our observations of this group last about 30 years. It includes several hundred patients with various forms of pre-ovarian absence of ovaries and post-state states.

The received results give the basis to speak about high efficiency of the principle of replacement therapy selected by us by preparations of female sex hormones. As a rule, full feminization of the phenotype is achieved: vegetative disorders characteristic of castration are eliminated; Inferiority complex due to lack of sexual development disappears; the patient can create a family.

Contraindications to substitution therapy for such drugs in this group of patients are very limited: it is an individual intolerance and severe liver disease.

After the removal of gonads about gonocytoma, there are no contraindications to postoperative substitution therapy for female sex hormones. On the contrary, these conditions are the basis for enhanced treatment, because gonadal tumors are hormone-dependent, and increased gonadotropic activity after castration is undesirable.

Complications of hormone replacement therapy were limited to individual intolerance to the drug, which required its replacement or transition to parenteral administration of estrogens. There were rare cases of relative hyperestrogenization (mastopathy, prolonged menorrhagia). As a rule, the connection of gestagens eliminated these phenomena.

Hormonal therapy of patients with male civil sex. If the male sex is selected for patients with various forms of hermaphroditism, and the development of male secondary sexual characters is slowed or insufficient, there is a lag in the "bone age" from the actual, there is a danger of forming eunuchoidism and violations of the castration syndrome type, there are complaints of sexual weakness, treatment with androgenic drugs.

Unlike patients with gonadal dysgenesis with a female phenotype, who require constant estrogen replacement therapy due to the lack of gonads, male sex is usually selected in cases where there is reason to assume the presence of androgenic activity of their own testicles. Therapy in these patients is not only substitutive. Sometimes it is necessary to stimulate the function of one's own gonads by gonadotropins. It should be remembered that overactive androgen therapy can cause undesirable suppression of endogenous gonadotropic activity and, as a consequence, a decrease in the function of already inadequate testicles. Therefore, it is better to limit the minimum for a given patient doses of androgens, introducing them with intermittent courses. In some cases, the alternation of treatment with androgens and preparations of gonadotropins is justified. According to the literature and our observations, the chorionic gonadotropin not only stimulates leydigov cells, but also increases the sensitivity of target tissues to the action of androgens. However, large dosages of gonadotropins can contribute to the development of hyalinosis of the seminiferous tubules.

Approximate schemes of hormone therapy.

• Continuous replacement therapy (with a female phenotype):
  • a) synestrol at 0.001 g (1 tablet) per day for 3-6-12 months;
  • b) microfolin-forte at 0.05 mg (1 tablet) daily;
  • c) microfolin-fort by 0.05 mg (1 tablet) per day constantly, 12.5% solution of oxyprogesterone capronate per 1 ml intramuscularly every 10 days for 3-6 months (when mastopathy occurs in patients with no derivatives of Müllerian structures) .
• Cyclic replacement therapy (with female phenotype):
  • a) microfolin forte at 0.05 mg (1 tablet) per day from the 1st to the 20th day of each month or from the 5th to the 26th day of the cycle;
  • b) microfolin-forte at 0.05 mg (1 tablet) per day from the 1st to the 15th day of each month or from the 5th to the 20th day of the cycle, pregnin to 0.01 g (1 tablet) 3 once a day sublingually from the 16th to the 21st day or from the 21st to the 26th day of the cycle;
  • c) infekundin (bisekurin, non-vellon, etc.) 1 tablet per day from the 1st to the 21st day of each month or from the 5th to the 26th day of the cycle;
  • d) infecondin (bisekurin, non-vellon) 1 tablet per day from the 1st to the 21st day of each month or from the 5th to the 26th day of the cycle, 12.5% solution of hydroxyprogesterone capronate 1 ml intramuscularly 16th day of infecundine intake;
  • e) methyltestosterone 0,005 g 1-2 times a day from the 1st to the 21st day or from the 5th to the 26th day of the cycle for 3-4 months under the tongue (for the development of secondary hair).
• Androgenation (with male phenotype):
  • a) methyltestosterone 0,005-0,01 g 2-3 times a day sublingually for 1 month. Breaks between courses - 2-4 weeks;
  • b) chorionic gonadotropin (choriogonin) 500-1500 ED intramuscularly 2-3 times a week, for a course of 10-20 injections, per year 2-3 courses;
  • c) Sustanon-250 (Omnadren-250) 1 ml intramuscularly once a month, constantly (with severe testicular failure as replacement therapy);
  • d) 10% solution of testanate per 1 ml intramuscularly once every 10-15 days permanently (replacement therapy).

Clinical examination of patients with congenital pathology of sexual development is a necessary condition for treatment. At the age of admission, the frequency of a doctor's visit can not be more than once a year. Particular importance of dispensary observation is acquired in prepubertate and pubertal, when the question of hormonal correction of physical and sexual development arises. Since the age of 7-8, an annual radiography of the wrists with radiocarpal joints is needed to assess the dynamics of maturation of the skeleton. With a significant lag in the bone age from the actual hormone therapy should start earlier. Of particular importance is the dynamics of bone age in patients with growth retardation receiving anabolic or sex drugs: rapid maturation of the skeleton requires a reduction in dosage or discontinuation of treatment. Against the background of taking sex hormones at pubertal age, patients should be examined at least 3-4 times a year, in post-pubertal and adulthood 2-3 times a year.

An important role in dispensary observation is played by psychological and sexological observation. Such patients hardly tolerate the change of the doctor, communication with other specialists. Trustful contact with a permanent doctor is especially important for them. It is necessary to emphasize the need to observe a strict medical secret of the diagnosis: involuntary disclosure of it can lead to severe excesses on the part of patients, up to suicidal actions.

Clinical follow-up should be carried out by an endocrinologist with the participation of a gynecologist, urologist and psychoneurologist.

The prognosis for life is favorable, with regard to social adaptation, it is determined by the correctness of the choice of sex (with intersexual states), the adequacy of substitutive and / or stimulating hormonal therapy, which ensures the development of the phenotype corresponding to the selected sex, the possibility of adaptation in society, normal sexual life and the creation of a family. The prognosis for stimulating fertility in the vast majority of patients is unfavorable. Patients who retain fertility are rare exceptions.

The incapacity of patients with congenital pathology of sexual development is undoubtedly limited in connection with the absolute or relative insufficiency of the anabolic action of sex hormones. With systematic adequate treatment, it improves. Its more significant limitations are sometimes observed in chromosomal diseases, Shereshevsky-Turner and Klinefelter syndromes, the "turnaround" form of the testicular dysgenesis syndrome. Some of these patients have defects not only somatic, but also mental development, which requires the selection of a specialty corresponding to their capabilities. However, the discipline, diligence and conscientiousness characteristic of the majority of such patients provide, as a rule, their labor adaptation. Only individual patients in connection with the peculiarities of the mental state need to be transferred to a disability.