Twelve healthy men were studied to ...

Twelve healthy men were studied to determine the meaning of ventilatory stimulation with chlormadinone acetate (CMA), a efficacious synthetic progesterone, in small doses (5 mg/day), in succession arterial blood gas levels. Using a randomized, double-blind, crossover trial, undivided week of CMA administration caused a significant reduction in arterial [COsub2] tension ([PaCO.sub.2]) by way of 4.1 [+ or -] 29 (SD) mm Hg The magnitude of the fall in [PaCO.sub.2] was about the same as that obtained with dose of 50 mg by day in our previous subject of attention These results indicate that the dosages of progestin and the force of the drug on ventilation were not in parallel, and it may provide the idea that larger doses of progestin would not necessarily be required to stimulate ventilation.

Progesterone has been implicated in the increased alveolar ventilation in women not and nothing else during pregnancy, but also in the luteral phase of menstruation.[1,2] Similarly, administration of synthetic progestin occasions an increase in minute ventilation and a decrease in [PaCO.sub.2] in normal subjects[3]

Progestin has been used therapeutically in near patients with chronic obstructive pulmonary disease[4] and in cases of alveolar hypoventilation syndrome accompanied on obesity.[5] Progestin MPA with dose of 60 mg by day has most frequently been used in many studies.[6-8] We have hitherto chosen a synthetic progestin CMA, which has ten times the luteinizing activity of MPA, and used 50 mg by day, because this dose was applied to patients with prostate hypertrophy[910] However, no obvious rationale to administer these dosages of progestin for a respiratory stimulant has been clarified.

The not past nor future study was undertaken in healthy male make liables to determine the effect of synthetic progestin in small doses (CMA, 5 mg/day) onward arterial blood gas levels. We used a randomized, double-blind, crossover placebo-progestin trial in this study

MATERIALS AND METHODS

Subjects

Twelve healthy men aged 23 to 27 years, participated in this reflection after their informed consent had been obtained. All enslaves were nonsmokers with normal spirometry, had no history of cardiopulmonary disease, and were taking no medication.

close attention Design

The close attention was a randomized, double-blind, crossover trial in 12 men during a three-week period. After initial arterial children gas determination and lung function exhibitions the subjects were randomized to receive either progestin (CMA, 25 mg bid) or placebo tablets of identical appearance for undivided week. Then, the line gas study was repeated and serum CMA concentration was measured at the same time to confirm that no progestin could be exposeed under placebo conditions or to confirm that make submissives surely took the drug below CMA conditions. All the enslaves spent washout period for united week. After that, the alternate blend was given for an additional week, and the thought was performed for a inferior time.

Statistical Analysis

Using a paired Student's t-test no systematic differences in the means of any variable measured were noted between the initial and placebo periods (p>01) We evaluated any difference between the issues of CMA and placebo forward arterial blood gas tension by way of a paired Student's t-test.

RESULTS

event of CMA administration on arterial descendants gas values and acid-base status are shown in Table 1 The [PaCO.sub.2] lay low in ten of 12 subdues by a mean of 41 [+ or -] 29 (SD) mm Hg (range, -- 12 to 86 mm Hg negative value means unexpect rise in [PaCO.sub.2] after CMA administration). Arterial pH watchs to become alkaline compared with that during placebo administration, and [[HCO-sub3]] significantly decreased, indicating progressive growth of chronic respiratory alkalosis. The [PaCO.sub.2] increased on 5.3 [+ or -] 65 mm Hg (range, -- 12 to 201 mm Hg negative value means unexpect fall in [PaCO.sub.2] after CMA administration). [TABULAR DATA OMITTED]

The relationship between the magnitude of the fall in [PaCO.sub.2] during CMA administration, compared with the placebo data, and serum CMA concentration measured by the agency of radioimmunoassay during CMA period is shown in Figure 1 No significant relation was institute between these two variables.

DISCUSSION

The springs of this study demonstrated that administration of synthetic progestin CMA in doses of 5 mg by day lowered the [PaCO.sub.2] 40 mm Hg in normal men The magnitude of this fall in [PaCO.sub.2] was about the same as that obtained with conventional dose of CMA in our previous report.[11] During CMA administration with dose of 50 mg/day, [PaCO.sub.2] decreased by the agency of 3.1 [+ or -] 26 (SD) mm Hg and plasma [[HCO-sub3]] decreased from 2.9 [+ or -] 11 mEq/L in ten healthy young men ranging in age from 20 to 25 years. These eventuates indicated that the effect of progestin onward ventilation were not in parallel with the dosages of the drug

It may well be that single of the possible determinants in ventilatory reply to progestin observed in our studies is attributable to the amount of the progesterone receptors. Although the exact mechanism of respiratory stimulation by means of progesterone is still unknown, the consequence is most likely exerted by the agency of directly stimulating the central nervous theory and an increase in ventilation appears to have a primary power from progestin.[8] It is unknown whether progesterone receptors are not away in tissues involved in ventilatory ascendency while they are known to exist in hypothalamus and pituitary in the central nervous system[12] However, stimulatory actions of progestin forward ventilation may be receptor-mediated, since steroid actions in target tissues are mediated on specific receptors.