Hormonal testing for miscarriage of pregnancy

The purpose of hormonal studies in patients with habitual miscarriage is to determine the causes of the formation of habitual miscarriage, the severity of hormonal disorders in order to select adequate therapy.

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

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

The second increase in estradiol concentration on the 21st-22nd day of the cycle is a reflection of the hormonal activity of the developing corpus luteum of the ovary. On the eve of menstruation, the estradiol content drops to the 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 reliable increase in progesterone levels to 47.7 nmol/l (1.5 ng/ml) is noted during ovulation. In the following days of the early luteal phase, the progesterone concentration continuously increases, reaching its maximum value by the middle of the luteal phase, then gradually decreases towards menstruation.

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

If the patient is suspected of having an incomplete luteal phase, it is necessary to determine the cause. For this purpose, a hormonal study is performed to exclude hyperandrogenism.

To detect hyperandrogenism, the level of cortisol in the blood plasma, the level of DHEAS, 17-hydroxyprogesterone, testosterone and prolactin are determined. These studies are necessary if a woman has hirsutism and other signs of virilization, irregular menstruation, a long cycle, oligomenorrhea, a history of non-developing pregnancies, intrauterine fetal death of unknown genesis, rare pregnancies.

It is noteworthy that the highest level of cortisol is observed in the early morning hours, this should be taken into account when prescribing glucocorticoids. If it is necessary to suppress the level of androgens in case of 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 suppress androgen production, it is better to prescribe glucocorticoids in the morning hours, and the action of glucocorticoids will occur with fewer side effects.

To detect adrenal hyperandrogenism, the level of dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxyprogesterone (17OP) is determined. To detect ovarian hyperandrogenism, the testosterone level is tested. If it is not possible to determine the androgen levels in the blood, the level of 17KS excretion in the urine can be tested. When interpreting the results, the obtained data must be compared with the standard parameters of a given laboratory. When determining the 17KS indicators, it is necessary to remind the patient of the procedure for collecting daily urine and the need to follow a diet excluding all red-orange products for 3 days before the test.

When determining the 17KS values above the standard in women with miscarriage, it is necessary to conduct a dexamethasone test for differential diagnosis of ovarian or adrenal hyperandrogenism. The test is based on the fact that the introduction of glucocorticoid drugs (prednisolone, dexamethasone) that inhibit the secretion of ACTH leads to a rapid and significant decrease in the excretion of 17KS in urine in adrenal hyperandrogenism. Taking into account that women with miscarriage have a biphasic cycle and the progesterone content changes significantly depending on the cycle phase, the dexamethasone test should be performed in the middle of phase I, i.e. on days 5-7 of the cycle, when mainly adrenal hyperandrogenism is detected. Two tests are used - small and large. With a small test, dexamethasone is prescribed at a dose of 0.5 mg every 6 hours for 3 days. Three days before the test, and on the 2nd-3rd day after the administration of dexamethasone, the daily excretion of 17KS is determined.

The major test consists of prescribing dexamethasone at a dose of 2 mg every 6 hours for 3 days (8 mg/day). The procedure is the same as the minor test. With a positive dexamethasone test, a decrease in the content of 17KS by more than 2 times (by 50% or more) compared to the initial value is noted, which is observed in adrenogenital syndrome.

In case of a positive test, the last dose of the drug does not change until the 17KS level is tested on the 22nd day of the cycle and on the 7th day of the next menstrual cycle. After the test, the final dose of the drug is determined to normalize the 17KS level or it is canceled. Under the influence of the test in ovarian hyperandrogenism or Cushing's syndrome, the 17KS level practically does not decrease, or it decreases insignificantly. It should be noted once again that miscarriage is characterized by latent forms of hyperandrogenism, with mild clinical manifestations of hyperandrogenism outside pregnancy, with a normal 17KS level, which complicates diagnosis. To determine the reserve capacity of the adrenal glands and the nature of their dysfunction, a test with prolonged-release ACTH (Synacte-depot 40 mg) is performed in the early follicular phase of the cycle. In response to ACTH stimulation in patients with mild forms of hyperandrogenism of adrenal origin, an inadequate increase in androgen excretion is observed: 17KS by an average of 100%, DHEA by 190%, and pregnanetriol by 160%.

In healthy women in the control group, an increase in 17KS by 46%, DHEA by 72% and pregnanetriol by 54% was noted. Thus, the excess of androgens in women with enzymatic insufficiency of the adrenal glands is different and depends on the degree of expression and the type of enzymatic defect. In patients with classical forms of adrenogenital syndrome, there is a deficiency of enzymes, and in latent forms of adrenogenital syndrome, cortisol synthesis is blocked to a lesser extent and can be detected in an inadequate response to ACTH stimulation. An increased level of androgens can be caused by both excessive production of androgens and a violation of their metabolism and binding in the periphery. Classical syndromes are characterized by excessive secretion of active androgens. In latent and mixed forms, excess androgen levels are often caused by changes in metabolism, the influence of various factors on the activity of enzyme systems, which causes the manifestation of an atypical clinical picture and complicates diagnosis and therapy.

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