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  • Title: Transitory hypoadrenalism due to long-term treatment with antiovulatory compounds.
    Author: Leiba S, Kaufman H, Winkelsberg G, Bahary C.
    Journal: Isr J Med Sci; 1979 May; 15(5):434-7. PubMed ID: 221439.
    Abstract:
    A considerable number of women receiving antiovulatory compounds or estrogens complain of weakness and fatigability, suggesting a state of clinical hypoadrenalism. For this reason, levels of plasma ACTH and plasma cortisol were determined in 25 women with such complaints both during treatment and at various intervals after cessation of this treatment. The results obtained showed that there was a significant inhibition of ACTH secretion during long-term treatment with antiovulatory compounds or estrogens, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis following interruption of the drug, supporting a state of transitory hypoadrenalism. 25 women who had been treated with antiovulatory compounds or estrogens were tested to determine the plasma levels of adrenal cortex hormone (ACTH) and plasma cortisol while the subjects were still undergoing treatment (23/25) and after treatment interruption (2/25). These determinations were made to establish a state of clinical hypoadrenalism resulting from use of oral contraceptives (OCs). During treatment with antiovulatory compounds or estrogens, plasma cortisol was significantly increased in 11 cases, and in another 9, it was within the upper range of normal. In contrast, the level of plasma ACTH was lower than normal or at the lower range of normal in 22/23 cases. 2 months after interruption of the OCs, only 11/20 patients who remained under follow-up had normal levels of plasma ACTH; the blood cortisol levels were also normal in 10 of these patients and higher than normal in one patient. These results indicate a normal rebound of pituitary-adrenal function. In 5 cases, ACTH levels were subnormal and cortisol levels were low normal or subnormal from 4-8 months after interruption of treatment, suggesting a state of secondary adrenal insufficiency. In these patients, the tendency to return to normal became apparent 3-4 months later. In 4 cases, the level of ACTH returned to normal earlier than that of plasma cortisol, suggesting a transitory adrenal insufficiency due to delayed normalization of adrenal function in comparison with that of the pituitary. A tendency to normalization of the cortisol secretion was also seen several months later in these patients. These results indicate that there was a significant inhibition of ACTH secretion during long-term treatment with OCs, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis after interruption of the drug, supporting a state of transitory hypoadrenalism.
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