Tactics of pregnancy management in adrenal hyperandrogenism

Treatment is carried out throughout pregnancy, taking into account the congenital defect of the pathology. If you stop taking dexamethasone, the pregnancy may not be interrupted due to the fact that the fetus will take over the supply of glucocorticoids. In this regard, there may be intrauterine hyperfunction of the adrenal cortex, and at the time of stress (birth process), the child may die. Atrophy of the adrenal cortex is found during pathological examination. Therefore, if under the influence of dexamethasone therapy, the level of 17KS decreases more than we would like, the dose of dexamethasone can be reduced to 1/4 tablet every other day, but stopping the intake is inappropriate. Particular attention should be paid to the terms of pregnancy of 13, 24 and 28 weeks. These terms are associated with the entry of fetal endocrine organs into active production, which can provoke increased production of androgens. On the 3-4th day after delivery, the dose of dexamethasone is gradually reduced and therapy is stopped on the 7-8th day after delivery.

In adrenogenital syndrome with normal 17KS or 17OP levels but elevated DHEAS levels, dexamethasone therapy can be administered only up to 16 weeks of pregnancy (counting from ovulation). By this time, the placenta has completed its development, and steroidogenesis already provides sufficient estrogens, so that the adrenal glands' share in their production is not so significant.

Prescribing progesterone drugs for hyperandrogenism of adrenal genesis is inappropriate, since they usually have hyperprogesteronemia. It is necessary to monitor the condition of the cervix, since isthmic-cervical insufficiency is possible, which is observed in 2/3 of pregnant women with adrenogenital syndrome, including with its erased manifestations. During pregnancy, fetal condition is monitored and placental insufficiency is prevented from the first trimester. When developing labor management tactics, attention should be paid to the features of the pelvic structure, since patients with hyperandrogenism have a pelvic structure with a narrowed outlet, which can complicate the course of labor. In case of an extremely burdened anamnesis, breech presentation and anatomical features of the pelvis, delivery by cesarean section is advisable. At the birth of the child, it is necessary to inform the neonatologist about the dose and duration of dexamethasone intake, since the child may have glucocorticoid withdrawal syndrome.

Considering that patients with adrenogenital syndrome can pass this gene to the fetus, prenatal diagnostics is necessary, which we conduct simultaneously with the diagnosis of Down's syndrome in the fetus. At 17-18 weeks, the mother's blood is tested to determine the levels of alpha fetoprotein, human chorionic gonadotropin and 17OP. With an elevated level of 17OP, it is necessary to do amniocentesis and determine the level of 17OP in the amniotic fluid. With a high level of 17OP, adrenogenital syndrome is diagnosed in the fetus. Unfortunately, modern tests can make a diagnosis, but it is very difficult to determine the severity of adrenogenital syndrome, which can range from a non-classical mild form of the disease to a salt-wasting severe form of adrenogenital syndrome. The question of whether to continue the pregnancy or terminate it due to adrenogenital syndrome in the fetus is decided by the parents.

If the mother does not have adrenogenital syndrome, but the husband is a carrier of the adrenogenital syndrome gene and there have been births of children with adrenogenital syndrome in the family, then the following tactics are accepted in world practice. The patient receives dexamethasone from the moment of pregnancy diagnosis (the earlier, the better) to prevent virilization in the fetus, if it is sick with adrenogenital syndrome.

Tactics of pregnancy management in patients with ovarian and mixed forms of hyperandrogenism

When pregnancy occurs, strict monitoring is necessary, since the most common complication is the threat of termination of pregnancy, according to our data, in 36 % of patients. Determination of the level and dynamics of chorionic gonadotropin, DHEA-S, 17KS, E2 and P is necessary for the selection of hormonal therapy.

Dexamethasone therapy should be offered to reduce the combined effect of androgens on embryo development. Hyperandrogenism disrupts embryo development to a much greater extent than the dose of glucocorticoids that we recommend - no more than 0.5 mg of dexamethasone. Given the history of NLF and those who underwent ovulation stimulation, it is advisable to prescribe Duphaston or Utrozhestan in normal doses. At low levels of chorionic gonadotropin, maintenance doses of chorionic gonadotropin can be administered. Prescription of hormonal drugs should be under the control of the level of 17KS. Prescription of Duphaston or Utrozhestan is indicated for relative hyperestrogenism, when the ratio of B and P is more than 1.5. If the ratio is in the normal levels, then treatment with gestagens can be omitted. We stop hormonal therapy with gestagens at 16 weeks of pregnancy, when the formation of the placenta is completed.

In the case of the ovarian form of hyperandrogenism, dexamethasone treatment can be stopped after 16 weeks, and in the case of the mixed form, it can be continued almost until the end of pregnancy - up to 35-36 weeks. Often, toxicosis of the second half of pregnancy can develop at the end of pregnancy (according to our data, this complication occurred in 34.2% of patients in these groups), and therefore we consider dexamethasone treatment not indicated after 35-36 weeks. However, in all cases of the threat of premature termination of pregnancy, glucocorticoid treatment should be continued.

During the second trimester of pregnancy, it is necessary to monitor the condition of the cervix due to the possibility of isthmic-cervical insufficiency, which, according to our data, accounted for 30.8%. Due to the fact that isthmic-cervical insufficiency is functional, it is necessary not only to monitor according to ultrasound data, but also to assess the condition of the cervix during a vaginal examination.

From the first weeks of pregnancy, prevention of placental insufficiency and possible activation of viral-bacterial infection is necessary.

Despite preparation for pregnancy, careful monitoring during pregnancy and rational therapy, 76.8% of women with ovarian hyperandrogenism, 77.8% with mixed hyperandrogenism and 92% with adrenal hyperandrogenism managed to maintain the pregnancy and successfully deliver a live child.

As a result of differentiated rehabilitation therapy in patients with different forms of hyperandrogenism, the frequency of secondary infertility decreased by 4 times (from 36.4% to 9.3%) and spontaneous abortion by 11 times (from 63.6% to 5.7%). The most optimal results of therapy were achieved in women with adrenal hyperandrogenism.

According to many researchers, after childbirth, the pathological symptom complex reappears in most women with hyperandrogenism. Currently, there are no treatment methods that can cure patients. Due to the fact that hyperandrogenism in the miscarriage clinic is less severe than in the infertility clinic, the issues of restoring menstrual and reproductive functions, taking into account successful and unsuccessful pregnancy, were of considerable interest.

The studies showed that the condition of menstrual and generative functions in the long term depended on both the pregnancy outcome and the form of hyperandrogenism. In women with interrupted pregnancy, menstrual function subsequently significantly worsened up to amenorrhea, hirsutism progressed, and a reliable increase in DHEA, prolactin, and cortisol in the blood plasma was noted. Most of them (67.7%) developed persistent secondary infertility, which was 8 times more common than infertility after successful childbirth.

Successful completion of pregnancy contributed to the restoration of the previously disturbed menstrual cycle in most women, stable normalization of androgen levels and favorable completion in 74.5% of normal repeated births without corrective hormonal therapy. Recurrence of spontaneous termination of pregnancy was in 15.7% of women with a mixed form of hyperandrogenism.

Successful completion of pregnancy in patients with hyperandrogenism with miscarriage indicates a functional nature of the disorders or a mild form of the pathological process. When assessing the state of target organs, taking into account successful births and unfavorable pregnancy outcomes, the following data were obtained: every third patient (31.4%) had hyperplastic processes in the uterus and mammary glands. In patients with mixed (35.7%) and ovarian (48%) hyperandrogenism, pathological processes in hormone-dependent organs were noted 3-4 times more often than in women with adrenal hyperandrogenism (11.9%).

Among patients with adrenal hyperandrogenism, fibrocystic mastopathy and thyroid diseases prevailed, while women with the ovarian form had hyperplastic uterine diseases and cardiovascular pathology. These diseases were 1.5-4 times more common in women whose reproductive function could not be restored. When assessing the condition of children born to women with hyperandrogenism, depending on the type of hyperandrogenism and the duration of glucocorticoid treatment during the period of formation of their reproductive function (from birth to 25 years), it was found that all children grew and developed normally, and there were no delays in mental and physical development. In the structure of the disease in children under 4-5 years, mild exudative diathesis, allergies and colds prevailed, while in older age groups, gastrointestinal tract and respiratory diseases prevailed, which most often affected the offspring of mothers with ovarian and mixed forms of hyperandrogenism. However, the specific gravity of these diseases did not exceed the frequency in the general population. A close connection was found between the frequency of these diseases and such factors as feeding characteristics, parents' tendency to the same pathology, the mother's age at the time of the child's birth (over 35 years old) and no dependence was found on the presence or absence, as well as the duration, of glucocorticoid therapy in the mother during pregnancy.

At the same time, the period of formation of menstrual and reproductive functions in the offspring of women with ovarian and mixed forms of hyperandrogenism who did not receive glucocorticoids was characterized by a number of complications: early and late menarche (25%), oligomenorrhea (36.6%), anovulation (33.3%), various endocrine disorders (45.4%), hirsutism (27.3%), small cystic changes in the ovaries (18.5%), and excess androgen levels (43.7%).