Hormonal studies on miscarriage

The goal of hormonal studies in patients with habitual miscarriage is to determine the causes of NLF formation, the severity of hormonal disorders for the selection of adequate therapy.

Considering the significant changes in the levels of sex hormones in the phases of the cycle, we conducted the studies on the 7-8th day of the I phase of the cycle and on the 21-23 day of the cycle (the 4th day of basal temperature rise).

The production of estradiol is characterized by a two-phase increase in its content in the blood during the menstrual cycle. In the early follicular phase, estradiol does not exceed 367 nmol / l (100 pg / ml). The maximum increase in its level is noted on the eve of ovulation, which reflects the functional activity of the mature follicle. In the following days, estradiol is reduced to 422.0 nmol / l (115 pg / ml); in the luteal phase of the cycle, the estradiol content gradually increases to figures slightly lower than the level of the hormone on the eve of ovulation.

The second increase in the concentration of estradiol on the 21-22 day of the cycle is a reflection of the hormonal activity of the developing ovarian yellow body. On the eve of menstruation, the content of estradiol drops to a level characteristic of the early follicular phase of the cycle.

The progesterone content in the follicular phase of the cycle does not exceed 15.9 nmol / L (0.5 ng / ml). The first significant increase in the level of progesterone to 47.7 nmol / l (1.5 ng / ml) is noted in ovulation. In the following days of the early luteal phase, the progesterone concentration increases continuously, reaching a maximum value by the middle of the luteal phase, then gradually decreases to menstruation.

The level of progesterone in blood plasma in the second phase of the cycle of 15.9 nmol / l (0.5 ng / ml) indicates ovulation, but only the progesterone level of more than 31.8 nmol / l (10 ng / ml) indicates a full function of the yellow body. The level of progesterone in the middle of the luteal phase is lower than 31.8 nmol / l, indicating the presence of an inferior luteal phase. However, often with a low level of progesterone in the peripheral blood, the endometrial biopsy performed at that time indicated a normal secretory transformation of the endometrium. Researchers explain this situation by the fact that progesterone is released in the pulse mode and the level in the peripheral blood does not correspond to its level in the endometrium. In addition, progesterone levels in peripheral blood in women with normal reproductive function and in patients with miscarriage in a large percentage coincide.

If the patient means an inferior luteal phase, the cause must be determined. For this, hormonal research is carried out to eliminate hyperandrogenism.

To detect hyperandrogenism, the level of cortisol in the blood plasma is determined, the level of DEAC, 17-hydroxyprogesterone, testosterone and prolactin. These studies are necessary in the presence of a woman with hirsutism and other signs of virilization, irregular menstruation, a prolonged cycle, oligomenorrhoea, in the presence of an anamnesis of undeveloped pregnancies, intrauterine fetal death of an unknown genesis, rarely upcoming pregnancies.

It is noteworthy that the highest level of cortisol is observed in the early morning hours, this should be taken into account in the appointment of glucocorticoids. If it is necessary to suppress the level of androgens in dysfunction of the adrenal cortex, it is advisable to prescribe glucocorticoids in the evening hours, so that the peak of their action coincides with the peak of cortisol secretion. If glucocorticoids are prescribed for autoimmune disorders and there is no need to inhibit the production of androgens, it is better to prescribe glucocorticoids in the morning hours, and the effect of glucocorticoids will occur with less side effect.

To detect adrenal hyperandrogenism, the level of dehydroepiandrosterone sulfate (DEAC) and 17-hydroxyprogesterone (17OP) is determined. To detect ovarian hyperandrogenism, the level of testosterone is examined. If there is no possibility of determining androgen levels in the blood, you can examine the level of 17C excretion in the urine. When interpreting the results, it is necessary to compare the obtained data with the standard parameters of this laboratory. When determining the 17KS indicators, it is necessary to remind the patient of the procedure for collecting 24-hour urine and the need to observe a diet for 3 days before the study, with the exception of all red-orange products.

When determining the indicators of 17KS above normative in women with miscarriage, a dexamethasone test should be performed for differential diagnosis of hyperandrogenia of the ovarian or adrenal origin. The test is based on the fact that the administration of glucocorticoid co-action drugs (prednisolone, dexamethasone) inhibiting the secretion of ACTH leads to a rapid and significant decrease in excretion in the urine of 17KS with hyperandrogenism of the adrenal genesis. Given that in women with miscarriage the cycle is mostly biphasic and the content of progesterone varies significantly depending on the phase of the cycle, the dexamethasone test should be performed in the middle of phase I, i.e. On the 5th-7th day of the cycle, when the predominantly adrenal hyperandrogenia is revealed. Two samples are used - small and large. At a small sample, dexamethasone is prescribed in a dose of 0.5 mg every 6 hours for 3 days. For 3 days before the test, daily excretion of 17C is determined on day 2-3 after the administration of dexamethasone.

A large trial consists in prescribing dexamethasone at a dose of 2 mg every 6 hours for 3 days (8 mg / day). The procedure is the same as for a small sample. With a positive dexamethasone sample, a decrease in the 17C content is more than 2-fold (by 50% or more) as compared with the baseline value, which is observed with adrenogenital syndrome.

With a positive sample, the last dose of the drug does not change until the 17K level is examined on the 22nd day of the cycle and on the 7th day of the next menstrual cycle. After the study, finally determine the dose of the drug to normalize the level of 17KS or it is canceled. Under the influence of the test with ovarian hyperandrogenism or Cushing's syndrome, a decrease in the level of 17C does not occur, or it decreases insignificantly. It should be noted again that worn-out forms of hyperandrogenia, with indistinctly expressed clinical manifestations of hyperandrogenia outside pregnancy, with a normal level of 17KS, are typical for miscarriage, which makes it difficult to diagnose. To determine the reserve capabilities of the adrenal gland and the nature of the violation of their function, a trial with ACTH prolonged action (Sinakte Depot 40 mg) is performed in the early follicular phase of the cycle. In response to stimulation of ACTH in patients with mildly expressed forms of hyperandrogenism of the adrenal genesis, inadequate increase in androgen excretion - 17KS on average by 100%, DEA by 190% and prednantriol by 160% - is observed.

In healthy women, the control group had an increase of 17% by 46%, DEA by 72% and pregnan triol by 54%. Thus, the excess of androgenic women with enzymatic adrenal insufficiency is different and depends on the degree of expression and on the type of enzyme defect. In patients with classical forms of adrenogenital syndrome there is a deficiency of enzymes, and with erased forms of adrenogenital syndrome the synthesis of cortisol is blocked to a lesser degree and can be detected in an inadequate response to stimulation of ACTH. The increased level of androgens can be caused both by excessive production of androgens, and by a violation of their metabolism and binding at the periphery. Classical syndromes are characterized by excessive secretion of active androgens. With erased and mixed forms, the excessive level of androgens is more often due to a change in metabolism, the influence of various factors on the activity of enzyme systems, which causes manifestations of an atypical clinical picture and makes diagnosis and therapy more difficult.

[1], [2], [3], [4], [5], [6]