Long-acting Steroid Research Articles

Use of biological model of isolated overloading of skeletal muscle for determination of anabolic effect of steranobols

1. A model for determining the anabolic effect of long-acting steroid preparations, which consists of isolated overloading of the skeletal muscles of the orus, m. soleus and m. plantaris, after sectioning of the tendon of m. gastrocnemius, was tested. 2. The method permits the use of animals of different weight, age, and sex, without castration. 3. A comparative study of the anabolic properties of a preparation of retabolyl using the proposed biological model and the generally accepted method of testing according to the change in the mass of m. levator ani showed that the model of an isolated overload can be used for a quantitative evaluation of the actual anabolic effect as a rather simple, sensitive, and informative method.

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 8:00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration. Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone. The basal cortisol level was not suppressed and the responsiveness to ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 5 mg betamethasone therapy. The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone in equivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression.

IS THERE A PLACE FOR CHEMICAL AND RADIATION SYNVECTOMY IN RHEUMATIC DISEASES?

Synoviorthesis has the same indications as surgical synovectomy. But it is easy to perform, can be repeated and does not leave any scars. It should be tied first. The choice of the product to be injected depends on the joint, the number of injections and the age of the patient. In all cases a long-acting local steroid should be tried first. In combination, osmic acid seems to potentiate the effect of the steroid. If osmium tetroxide damages the cartilage, it has been demonstrated that the damage is limited and superficial and as far as we know without clinical consequence. The fear of side-effects has limited the use of synoviortheses in the United States. Sledge et al. (1977), in animals, have used a new rare earth isotope, dysprosium-165, a beta-emitter with a maximum tissue penetrance of 5.7 mm and the advantage of a very short half-life of 140 minutes. In so far as systemic therapy is only partly successful there is still a place for chemical and radiation synovectomy in rheumatic diseases.

236. Long-acting systemic steroids in contraceptive practice

Regularly administered combination-type oral contraceptives are the most effective contraceptives with good cycle control. The need for sustained motivation and the dropout rate of nearly 50% in India makes the present search for a depot hormonal preparation essential. Clinical data and discovered problems with 2 long-acting preparations are described. Tests were conducted with a 6-month subcutaneous implant (silastic or biodegradable) of Norethindrone acetate and with monthly injections of a combination of Norethisterone enanthate and estradiol valerate. Accidental pregnancy rates with both types of medication were high increasing toward the end of the period with the implant. Unpredictable irregular bleeding was the main reason for dissatisfaction with both medications. Low body weight was related to high side effect and pregnancy rates with the implant. It is concluded that depot preparations are still in a primitive stage of development. Work remains to be done on them.

Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: Norethisterone oenanthate and medroxyprogesterone acetate: 2. Bleeding patterns and side effects

The present paper reports the bleeding patterns and side effects experienced by women using norethisterone oenanthate (NET-OEN) and depot-medroxyprogesterone acetate (DMPA) in a WHO-sponsored comparative trial. Only a small minority of women had consistently normal cycles: the vast majority experienced some menstrual abnormality, with 47% of NET-OEN and 70.6% of DMPA users not having any normal cycles. Amenorrhoea was significantly more frequent with DMPA than with NET-OEN and its incidence increased with time. At the end of one year 35% of DMPA and 8.6% of NET-OEN users had total amenorrhoea. There were only minor differences between the two drugs with respect to the frequency or duration of bleeding episodes, but DMPA caused significantly more spotting than NET-OEN. With both treatments there were large individual variations and the bleeding pattern was totally unpredictable. Headache, the most important nonmenstrual side effect, was reported by 6.9% of the NET-OEN and 10.7% of the DMPA users. In the case of DMPA its incidence increased with time. Other complaints such as abdominal discomfort and nervousness were reported with similar frequency on both drugs. There was, with both treatments, a slight increase in body weight and a decrease in blood pressure.

Assay of long-acting contraceptive steroid formulations in rabbits

The duration of action of long-acting injectable formulations of gestagens was assessed in rabbits by measuring blood levels of the gestagen. Norethisterone oenanthate was rapidly absorbed and metabolised and norethisterone was detectable in plasma for up to 60 to 70 days. After administration of Depo-Provera, plasma levels of MPA were detectable for up to 110 days and after injection of norgestrel pelargonate, norgestrel was detected in plasma for a similar period of time. Org 2154 was slowly metabolised and plasma levels of the free gestagen were detectable for more than l80 days. The order of duration of activity is compared with results obtained in baboons and humans. The rabbit may serve as a suitable animal model for predicting the duration of action of injectable formulations in humans.

A rational approach to the use of epidural medication in the treatment of sciatic pain.

The results of a series of 120 epidural injections given as treatment for backache and sciatica using Methylprednisolone and local anaesthetic, performed in the Gloucestershire area, are presented and compared with other published results. Wide variations in the results of this treatment are found and these may in part be explained on the basis of the variable severity of the histological changes known to occur in and around nerve roots in cases of sciatica. The pathogenesis of sciatica in lumbar disc disease is discussed in relation to its treatment by epidural injections of a long-acting steroid. It is shown that the treatment is more successful in acute onset cases and cases that have epidurals within 6 months of the onset of symptoms and it is suggested that earlier epidurals are given in cases that do not respond to the usual conservative measures. Manipulation of the spine and sciatic stretch should not be carried out at the same time as the epidural, as these procedures may adversely affect the results in some cases and certainly tend to make them more difficult to assess.

Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: Norethisterone oenanthate and medroxyprogesterone acetate: 1. Use-effectiveness

Multinational comparative clinical evaluation of two long-acting injectable contraceptive steroids: Norethisterone oenanthate and medroxyprogesterone acetate: 1. Use-effectiveness

Short-Term Effects of Norethisterone Oenanthate and Medroxyprogesterone Acetate on Glucose, Insulin, Growth Hormone, and Lipids

The effects on carbohydrate and lipid metabolism in 24 healthy female subjects of the long-acting steroid contraceptives norethisterone oenanthate (200 mg) (11 subjects) and depo-medroxyprogesterone acetate (150 mg) (13 subjects) were studied. The subjects were between the ages of 18 and 25 years, with a history of normal menstrual periods. Pretreatment levels of plasma cholesterol, plasma triglycerides, phospholipids, blood glucose, insulin, and growth hormone were compared with those obtained 3 weeks and 12 weeks after the initial injections. There were no statistically significant differences from the pretreatment levels in any of the values obtained at 3 weeks and 12 weeks in either group.

A new class of long-acting hormonal steroid preparation: synthesis of dimeric androgens coupled at C 3-C 3 and C- 17-C 3 and of an androgen-progestogen combination

3β-Hydroxy-4-androsten-17-one was prepared from 4-androsten-3, 17-dione according to the method of Klimstra and Colton (1) and dimerized by means of esterification with succinic acid. The reduction with lithium-tri-t-butoxyaluminium hydride gave a testosterone derivative coupled between C 3-C 3 which showed after a single Injection of 10 mg a protracted but relatively weak androgenic effect in castrated male rats. The direct esterification of testosterone hemisuccinate with 4-androsten-3β,17β-diol gave the testosterone derivative coupled between C 17-C 3 which showed a more even and more protracted time response curve than testosterone enanthate. The testosterone-ethynodiol succinate also coupled between C 17-C 3, showed an androgenic depot-effect similar to that of the dimeric C 17-C 3 testosterone derivative.

皮膚科領域におけるコルチコイド全身投与の再評価

Systemic corticosteroid therapy was re-evaluated. Short-acting steroids, such as prednisolone, are preferred to long-acting steroid in prolonged steroid therapy. Steroids are indicated primarily in self-limited diseases, not responsive to other therapies. On the other occasions, it is advisable to withdraw from steroid therapy at least within one month. On the methods of administration, much thought should be given to the initial dose, methods of reduction, withdrawal and time of administration. Severe and interesting side effects of steroid therapy were mentioned.

69. Biological effects of a new long-acting piogestational steroid: Org 2793

69. Biological effects of a new long-acting piogestational steroid: Org 2793

Biochemical studies with once-a-month contraceptive pill containing quinestrol-quingestanol acetate

Biochemical study of a long-acting oral steroid formulation, containing 2.0 mg quinestrol and 2.5 mg quingeatanol acetate, was undertaken during a period of 24 Months. Hemoglobin, packed cell volume, liver function studies and serum proteins have not shown significant changes while significant increases in serum triglycerides, free fatty acide, phospholipide and cholesterol were observed during the therapy. The elevation in serum lipids was almost of the similar Magnitude as observed in daily combination pills.

A new class of long-acting hormonal steroid preparation: Synthesis of dimeric ethynodiol and nortestosterone, of dimeric and trimeric androgens and of some dimeric combinations of steroids

Dimeric steroid esters containing an estradiol molecule coupled with a molecule of ethynodiol, cortexo lone, or ethinylandrostenediol respectively, were synthesized. The same method was also used for dimerization of ethynodiol, nortestosterone, and testosterone, and for the preparation of a trimeric androgen consisting of two molecules testosterone linked by one molecule 5-androstene-3β, 17β-diol. The method is based upon the direct esteriflcation of steroid alcohols with steroid hemisuccinates in the presence of N,N'-carbonyldiimidazole. The results of preliminary experiments concerning the biological activity of some of these compounds showed a considerable prolongation of hormonal effect as compared to the respective monomer.

372. Influence of injectable steroid contraceptives on tissue lipids of female guinea pigs

Unlike oral steroid contraceptives metabolic effects of long-acting injectable steroid contraceptives have not yet been reported. It was therefore planned to study the influences of long-acting steroid contraceptives on lipids since steroids being fat soluble are localized in adipose tissue. Fertile female guinea pigs were injected im with .1 ml/animal/month of either a mixture of dihydroxyprogesterone acetophenide and estradiol-17-enanthate (mixed group) or medroxyprogesterone acetate Depo-Provera (DP group). Animals in the control group received normal saline. 3 weeks after the 3rd injection the animals were killed and the serum liver heart and ovaries analyzed for cholesterol (Chol) total and differential phospholipids (PLP) and triglycerides (TG). All these tissues were also examined histopathologically. The results show that in the mixed group there was a significant decrease in Chol PLP and TG in serum; and in the DP group only serum Chol was significantly increased. Levels of TG in the liver of both the treated groups were elevated. The TG of heart only in the DP group was elevated. Since there was no effect on serum free fatty acid levels it appeared that the increase in tissue TG is the result of an influence on synthesis and/or transport. Histopathological examination showed follicular degeneration with arrest of corpus luteum and ova were absent or necrosed. There was no histological evidence of fatty infiltration of the tissues examined. (FULL TEXT)

12. A new class of long-acting hormonal steroid preparation: synthesis of oligomeric steroid derivatives

12. A new class of long-acting hormonal steroid preparation: synthesis of oligomeric steroid derivatives

A new class of long-acting hormonal steroid preparation: Synthesis of oligomeric estradiol derivatives

A method for the synthesis of dimeric, trimeric and tetrameric estradiol esters is described. It is based on the esterification of the OH-groups of estradiol-17β or estradiol-17β-acetate with 3-acetoxy-estradiol-17β-hemisuccinate as carboxylic acid component in the presence of N, N'-carbonyldiimidazole. Preliminary biological tests have shown that these compounds possess a very protracted estrogenic activity when administered s.c. to the oophorectomized rat. A single injection of 40 μg/rat of the trimeric estradiol derivative e.g. brought about vaginal estrus for 120 days as compared to 80 days when estradiol undecylate was used.

Life table analysis of a clinical study of a once-a-month oral steroid contraceptive: Quinestrol — Quingestanol

A clinical study of a long-acting oral steroid formulation, containing 2.0 mg quinestrol and 2.5 mg quingestanol acetate, was undertaken during a 31-month period. A total of 212 women were enrolled in the study and 2,781 women-months experience was accumulated. Life-table analysis of event rates at the end of 1 year revealed the event rates for discontinuation to be 7.3 for pregnancy, 11.2 for abnormal bleeding and 17.3 for other medical reasons. The cumulative continuation rate at the end of 1 year was only 46.9, indicating this method was not well accepted in this population group.

Parenteral Medroxyprogesterone as a Contraceptive Agent

From April 1967-December 1968 depot-medroxyprogesterone acetate (DMPA) a long-acting contraceptive steroid was injected intramuscularly in 150-mg doses every 3 months to 650 women at the Emory University Family Planning Clinic for a total of 5082 women-months of use. No pregnancies occurred. Calculations based on life-tables show a continuance rate of 56.8% after 1 year. Terminations of treatment (43.2%) were due mainly to irregular bleeding (13.5%) including amenorrhea (2.8%) and other medical (5.5%) and non-medical (14.6%) problems; 6.8% were lost to follow-up. Due to high rates of effectiveness and continuation DMPA is considered an acceptable and effective contraceptive method.

Renal effects of a new anabolic steroid (29'038-Ba) in old age

The renal effects of 29'038-Ba, a new long-acting injectable anabolic steroid, have been studied in a group of fifteen elderly subjects with normal or impaired renal function. Renal clearances of inulin and endogenous creatinine, the estimated renal blood flow, and the TmPAH were increased by 16.8, 17.2, 17.9 and 35.3 percent respectively after administration of a total of 400 mg of this compound, in contrast to non-significant changes of CPAH and maximal concentrating capacity. No disturbances of liver function were observed in any of the subjects studied. No general side-effects were noticed except for transiently increased libido, reported by three female subjects in the middle of the treatment-period.