The Effect of Progesterone on the Respiration of Patients With Emphysema and Hypercapnia*

Abstract

The possibility that progesterone could influence breathing was first suggested by studies investigating the respiration of pregnant women. In 1912 Leimdorfer, Novak and Porges (1) found that the alveolar concentration of CO2 was lower in pregnant women than it was in the same individuals when they were not.pregnant. These observations were amplified and confirmed in 1915 by Hasselbalch and Gammeltoft (2). Beginning in 1947, Dbring, Heerhaber and co-workers (3-5) investigated the effect of pregnancy in lowering the alveolar CO2 tension and later extended the studies to measurements of CO, tension made during the normal menstrual cycle. They were able to show that the alveolar CO2 tension was depressed in the luteal phase of the cycle and that if pregnancy occurred this depression continued throughout gestation, rising shortly after delivery. This suggested to them that progesterone might play a role in the genesis of the decrease in alveolar CO2 tension and they were able to show that 50 mg. of progesterone given intramuscularly to normal men caused a stimulus to breathing which reached its maximum about 12 hours after injection.Persistent hypercapnia is a frequent finding in the terminal stages of chronic pulmonary disease. Present long-term methods for lowering this hypercapnia are not satisfactory. Since Daring and Heerhaber's studies were limited to single injections of progesterone, and because the effect of progesterone on respiration in the presence of hypercapnia was not known, the following studies were done to investigate the effect of repeated injections of progesterone on the respiration of patients with chronic pulmonary disease and elevated levels of arterial pCO2. In an attempt to evaluate

Ventilation during sleep onset

“…Ventilation has been increased (Cullen, Brum & Reidt, 1959;Lyons & Huang, 1968;Tyler, 1960), along with the partial pressure of oxygen (Kryger, McCullough, Collins, Scoggin, Weil & Grover, 1978b;Lyons & Huang, 1968;Morrison & Goldman, 1979;Sutton, Zwillich, Creagh, Pierson & Weil, 1975;Orr, Imes & Martin, 1979) and oxy-haemoglobin saturation (ICryger et al 1978b;Lyons & Huang, 1968). In addition, carbon dioxide levels have consistently decreased (Kryger et al 1978b;Lyons & Huang, 1968;Morrison & Goldman, 1979;Sutton et al, 1975;Tyler, 1960).…”

Determinants of Chronic Carbon Dioxide Retention and Its Correction in Humans

“…Efficacy of treatment in patients with chronic obstructive pulmonary disease (COPD) and chronic CO2 retention have been less consistent (10,11). Lyons described some emphysematous patients who benefited from progesterone, whereas other patients described subjective discomfort due to dyspnea despite improved arterial blood gases (12).…”

Progesterone stimulates respiration through a central nervous system steroid receptor-mediated mechanism in cat.

“…Because the level of circulating progesterone correlates positively with increased ventilation, progesterone has been proposed as the ventilatory stimulant in these conditions (4)-a contention further supported by studies in which exogenously administered progesterone caused hyperventilation in normal male subjects (5,6) and in patients with breathing disorders (7)(8)(9)(10)(11)(12).…”