In: Respiratory4 Sep 2014
The prolonged effect of MPA observed in the present study could also be explained by the fact that we, unlike most others, only included female patients. Although progesterone and estrogen levels in postmenopausal women correspond to those of men, there is a marked difference in serum LH and FSH concentrations. Hormone replacement therapy is therefore likely to have a much more complex and interactive role with trophic effects in women. For example, estradiol increases the number of progesterone receptors. In ovariectomized rats, MPA does not stimulate breathing until progesterone receptors are upregulated with estrogen. In healthy men, the parenteral progesterone-induced decrease of PAco2 was not enhanced but prolonged when estrogen was combined. MPA metabolites may have weak intrinsic estrogenic activity or may be partially converted to estrogens.
We administered MPA 60 mg daily, which is the most common dose in studies using MPA to stimulate respiration. There is marked individual variation in the dose of MPA required for respiratory stimulation, the minimum dose ranging from 7.5 to 60 mg/d. The sustained effects of MPA could be attributed to slow elimination of MPA in our patients. This is not supported by the observations that MPA concentrations are below or near the detection limit after 216 or 3 weeks (our study) of cessation of the MPA therapy. Formation of long-acting active metabolites of MPA could be another explanation. MPA has many metabolites, the physiologic significance and biological activity of which are largely unknown. The turnover of MPA may also differ in various tissues. In rats, the MPA-related substances disappear slowly from the lung, skeletal muscle, and brain. Source
Progestins increase the ventilatory response to hypercapnia and hypoxia. The time course of increased chemosensitivity is not known. The prolonged effect of MPA may be caused by modification of peripheral or central chemoreceptor action or by central processing of the carotid body neural out-put. It is possible that MPA resets the respiratory center for a new response level, which is preserved for a prolonged period. Long-term effects may also arise from changes in the body CO2 stores and the acid-base buffer system acquired during 2 weeks of high-dose MPA. Finally, short-term MPA may alter the endocrinologic steady state, which may need weeks to recuperate.
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