Long-term Steroid Administration Research Articles

Regression of pathologic changes induced by the long-term administration of contraceptive steroids to rodents.

The induction of pathologic changes with hormone steroids has been studied in rodents, although comprehensive studies are lacking on the potential reversibility of these lesions. For these purposes, groups of rats were treated with quingestanol acetate and quinestrol, a progestogen-estrogen combination, for 50 weeks and observed for a subsequent 30-week period. Treatment resulted in a significant body weight gain suppression and reduction of food consumption which recovered after withdrawal. Other significant treatment-related effects were hair loss, ataxia due to pituitary enlargement, mammary chain masses with histologic adenocarcinoma, lens opacities, ovarian atrophy with follicular arrest, and uterine atrophic changes with suppurative inflammation throughout 50 weeks. Cessation of treatment did not effect hair loss or lens opacities, while mammary chain masses decreased in size and in incidence; mammary gland tumors showed regressive changes including the disappearance of adenocarcinoma, and the incidence of ataxia diminished together with reduced pituitary weights. Chromophobe cell hyperplasia with decreased eosinophils and acidophils and hemorrhage into the pituitary was observed up to 50 weeks and the tinctorial affinity of basophils and acidophils returned after withdrawal. Ovaries and uteri, which become atrophic and sustained chronic suppurative inflammation in the treatment phase, showed reduction of inflammatory reaction and disappearance of suppuration after withdrawal, and endometrial regeneration occurred with luteal cells seen in the ovaries. These results revealed the regressive characteristics of some of the mammary gland carcinomas as well as steroid-induced endocrine and pathologic lesions other than tegumentary and ocular changes in rats receiving high levels of steroids for prolonged periods of time.

Steroid-induced fractures and bone loss in patients with asthma.

To study the association between bone disease and long-term steroid administration in asthmatics, we reviewed the hospital records of 128 patients over 40 years of age who had taken daily or alternate-day adrenal corticosteroids for at least a year and compared them with the records of 54 other asthmatics of similar age who had not required long-term administration of steroids. We found evidence in the records of a total of 58 fractures of the ribs or vertebrae in 14 of the patients who had received long-term steroid treatment (11 per cent) and no evidence of fractures in the patients who had not received long-term treatment. We also prospectively studied 30 hospitalized asthmatic patients between 20 and 70 years of age who had been screened for medications (other than steroids) or complicating diseases known to affect bone mineralization. Eight of 19 asthmatic patients receiving long-term steroid therapy had rib or vertebral fractures, whereas none of 11 matched patients not receiving such therapy had fractures. Furthermore, bone-density measurements of the distal and proximal radius by photon absorptiometry revealed that the trabecular, but not the cortical, bone mass was below normal in the former group of patients but not in the latter. Within the long-term steroid group, there was no significant correlation between bone density and dose or duration of steroid treatment. We conclude that long-term steroid therapy in asthmatic patients is associated with decreased trabecular bone density and an increased prevalence of rib and vertebral fractures.

Long-term corticosteroid effect on lymphocyte and polymorphonuclear cell function in asthmatics

The effect of long-term alternate-day steroid administration on lymphocyte and polymorphonuclear cell (PMN) functions was studied in 10 steroid-dependent adult asthmatic patients. The duration of alternate-day prednisone usage ranged from 3 to 12 yr with an average of 6.7 ± 3.6 yr. Maintenance steroid dosage at the time of study ranged from 20 to 50 mg on alternate days, averaging 31 ± 8 mg. Prednisone caused marked lymphopenia, suppression of phytohemagglutin (PHA) lymphocyte transformation and PMN adherence 4 hr after ingestion. By 24 hr these measurements returned to normal or higher. These effects appeared at all doses between 20 and 50 mg of prednisone. In contrast, there was no statistically significant suppression of the total leukocyte count, total and active erythrocyte (E) rosette-forming lymphocytes, serum immunoglobulin concentrations, polymorphonuclear cell (PMN) phagocytosis, or delayed skin reactivity. We conclude that the acute effects of prednisone on lymphocyte and PMN function are transient and return to normal levels by 24 hr. The continued administration of beclomethasone dipropionate by inhalation did not interfere with the recovery of the transient leukocyte abnormalities induced by oral prednisone.

Acceptability of long-term contraceptive steroid administration in humans by subcutaneous Silastic capsules

Capsules of silicone rubber each containing approximately 18 mg. of megestrol acetate (MA) were implanted subcutaneously in 24 women. During the first portion of this study the patients were wearing IUCD's. Four different dosage groups were studied. Pregnancies occurred in patients who received one or two implants but not in those bearing either four or six capsules. Clinical, histologic, and cytologic data suggested that ovulation was not suppressed by four or fewer implants. The data suggested that there was frequent inhibition of ovulation in the patients bearing six implants. The patients' subjective reaction to this new technique was favorable. There were no local or systemic complications attributable to the implants. It is suggested that fewer than six implants of this size may provide acceptable long-term contraception without the inhibition of ovulation.

Experimental studies on the direct action of steroid hormones on ovarian function. 2

In the first report, it was demonstrated that the long-term administration of sex steroids (estrogen and progesterone) inhibited the ovarian function not only by the so-called feed back mechanism but also by the direct action on ovaries of mature and immature albino rats.In order to determine the direct action of those steroids on ovaries exactly, in this experiment, I used the hypophysectomized female albino rat without the endogenous gonadoropin release. After the long-term administration of estradiol benzoate or progesterone, combined gonadotropin injection could not induce the ovarian cholesterol and ascorbic acid depletion, which were detectable in the control animal group without the sex steroid administrations.From these experimental results, I conclude that under some conditions ovarian sex steroids, namely estrogen and progesterone, control the steroidogenesis in ovaries themselves through the reduction of reacitivities to gonadotropic actions.

Body composition during long-term administration of cortisone and anabolic steroids in an asthmatic subject

Metabolic balance studies were performed during 20 months in a male, asthmatic subject, who had developed muscular atrophies and osteoporosis during treatment with cortisone. Cortisone administration was continued during the whole investigation and, during one part of the study, an anabolic steroid, 19-nortestosterone-phenylpropionate, was also given. Exchangeable potassium and sodium were determined repeatedly by isotope dilution using K 42 and Na 24. Dermal potassium and nitrogen losses were determined. In the latter part of the study, dermal losses of calcium were also estimated. Body cell mass (BCM) increased initially with clinical improvement and adequate food intake and did not decrease during the continued cortisone treatment. Anabolic treatment did not result in a larger BCM than could be attained without such treatment. Muscular atrophies persisted. The calcium balance was initially slightly positive on an intake of 1700 mg./day and was not influenced by anabolic treatment. An increase in the calcium intake to 2600 mg./day led to calcium retention. Dermal potassium and nitrogen losses amounted to an average of 10 mEq. of potassium daily and 0.9 Gm. of nitrogen. Due to such losses, the results of the orthodox balance studies were highly misleading. Dermal calcium losses were small and amounted to an average of 40 mg./day.

A case report of Wegener's granulomatosis

A case of Wegener's granulomatosis in 37 year- old male was reported. The patient died due to respiratory failure after one year from the onset.Remarkable clinical findings were exophthalm-us, voluminous crust accumulation in nasal cavity, plication were unremarkable.Presence of bronchial asthma and chronic sin-usitis in past history, alluded to the possible rela-tionship of these diseases to Wegener's granuloma-tosis.The patient had tonsillectomy in the past. It seems that a further investigation should be made as to the relationship of tonsillectomy and thymo-lymphatic system to the etiology of the rare dise-ase, though it has been hardly referred to in the literature.In regard to the treatment, Co60 irradiation, long-term administration of steroids and carcinost-atic agents more or less brought about symptomatic relief, while autovaccinization with staphylococcus aureus cultured from intranasal crusts was found to be ineffective.The autopsy revealed necrotizing granulomato-us lesions in nasal cavity, orbita, upper and lower respiratory tract, lung, and skin.Microscopically, angitis and thrombus were found in the lesions of respiratory tract, lung and skin.

Steroids in Nephrotic Syndrome-Reply

To the Editor:— In answer to Dr. Rugstad's comments, I do agree with him that the rate of recovery from the nephrotic syndrome in children can, to a certain extent, be determined by the duration of the disease process. In fact, the data of our publication in question seem to support this contention for the first time. To shorten the duration of this variable disease has thus been our aim. How else could this be achieved today than by earlier institution of intensive long-term steroid administration? I do not assume that 29 of 34 nephrotic children given a placebo within 3 months after onset of their disease would be free of any detectable renal pathology over several years of observation. All available data up to 1954, when long-term, intensive regimen of steroid treatment of the nephrotic syndrome was first started in the United States, speak against such a possibility.

Acute Pancreatitis and Steroid Therapy-Reply

To the Editor:— It is not too surprising that long-term steroid administration may result in damage to the pancreas. The primary purpose for reporting the recent cases of acute pancreatitis which occurred during steroid therapy was to point out that this complication should be considered when a patient on steroid treatment develops abdominal pain. I agree that gratifying relief of pain and defervescence of fever may result from the use of steroids in the initial treatment of acute pancreatitis. On the other hand, I feel there is some question regarding the occurrence of a possible deleterious effect on the pancreas even after short-term courses of steroids. In one instance, a 21-year-old male developed symptoms of pancreatitis after only 14 days of prednisone ( 60 mg. per day ). A 16-year-old girl developed severe pancreatitis after 17 days of prednisone therapy with a dose no greater than 30 mg. per day. This week