Several lines of evidence indicate ...

Several lines of evidence indicate that synthetic progestins are relatively able-bodied long-term ventilatory stimulants and, thus, may be useful in the correction of chronic [COsub2] retention. First, medroxy-progesterone acetate (MPA) increased tidal body and lowered [PCO.sub.2] despite the vicinity of potentially powerful inhibitory influences including peripheral vital current and cerebrospinal fluid alkalosis in normal subjects[1] and plain mechanical impairment in patients with COPD[23] secondary in selected patients with COPD long-term MPA therapy was more consistent than chronic metabolic acidosis in correcting [COsub2] retention.[3] Therefore, progestins are unique ventilatory stimulants which cause hyperventilation in health and disease states independent of measurable changes in classic chemical stimuli.

The mechanism of ventilatory stimulation by way of progestins is not mediated through the level of progestational activity. a certain quantity of hormones with marked progestational activity as it is as anhydrohydroxyprogesterone or 19-norethinyltestosterone present to view no stimulatory effect on ventilation.[2] MPA has 15 times the progestational activity of progesterone and over and above the ventilatory response in normal males treated with MPA is half that observ during pregnancy. Chlormadinone acetate (CMA) has ten times the luteinizing action as MPA if it be not that produces the same amount of ventilatory stimulation.[4] In this issue of Chest (p 1073) Tatsumi et al report that CMA was used at common tenth the dose previously reported and caused a similar extent of ventilatory stimulation. A character for estrogen-inducible progesterone receptors has been propos as the reason for the variable ventilatory answer in human studies and between species.

Selection criteria are necessary to predict a ventilatory answer in patients with chronic [COsub2] retention. Patients with obesity-hypoventilation syndrome[5] and chronic mountain polycythemia[6] are advantageous candidates for progesterone therapy. Patients with COPD and strait-laced mechanical limitation ([FEV.sub.1]<0.5 L) and those who are unable to lower [PaCO.sub.2] greater than 5 mm Hg with voluntary hyperventilation are unlikely to correspond to long-term ventilatory stimulation.[3] Patients with acute ventilatory failure to be paid to a deterioration of lung function are les likely to benefit because of the predominant contribution of mechanical and ventilation-perfusion impairment rather than an insufficient inspiratory effort. Patients with primary alveolar hypoventilation do not suit consistently. Patients with obstructive be dead apnea do not benefit from progesterone[7] However, the part of progesterone in patients with nap apnea and daytime [CO.sub.2] retention is les well defined. A beneficial issue of synthetic progestins in the treatment of central be dead apnea is suggested by studies of periodic breathing at high altitude, since MPA caused a reduction in oscillations in oxygen saturation.[8] These clinical observations indicate that progesterone is an effective ventilatory stimulant in patients who have an inadequate inspiratory effort relative to the quality of mechanical and ventilation-perfusion abnormality.

Patients with COPD who correct their [COsub2] retention report either no increase or a decrease in dyspnea. Noncorrectors with more harsh mechanical impairment may experience an increase in dyspnea. Clinical improvement is occasionally dramatic, further is not well correlated with improvement in family gas values. Decreased libido and impotence arise in about 20 percent of patients.

The use of long-term progesterone therapy in patients with [COsub2] retention is limited, especially in patients with COPD because the long-term consequence of ventilatory stimulation on oxygen delivery and pulmonary hypertension has not been well documented. In contrast, improvement in tissue oxygenation is hinted in patients with obesity-hypoventilation syndrome and chronic mountain polycythemia, according to a decrease in hematocrit following improvement in [PaO.sub.2]. Widespread use of synthetic progestins is further limited on the small number of patients whose [COsub2] retention is befitting to an insufficient inspiratory effort rather than to a predominantly mechanical or neuromuscular abnormality.

James B Skatrud, MD Madison

REFERENCES

[1] Skatrud J Dempsey J Kaiser D Ventilatory answer to medroxyprogesterone acetate in normal subjects: time course and mechanism. J Appl Physiol 1978; 44:939-44

[2] Tyler JM The drift of progesterone on the respiration of patients with emphysema and hypercapnia. J Clin Invest 1960; 39:34-41

[3] Skatrud J Dempsey J Relative effectiveness of acetazolamide versus medroxyprogesterone acetate in correction of chronic carbon dioxide retention. Am Rev Respir Dis 1983; 127:405-12

[4] Morikawa T Tanaka Y Maruyama R Nishibayashi Y Honda Y Comparison of couple synthetic progesterones on ventilation in normal males: CMA v MPA. J Appl Physiol 1987; 63:1610-15