After many years of use and a large number of publications there is still no good evidence to indicate that progestogens have a valid role in the treatment of patients with a history of abortion. In many of the published series the amount of material administered has been inadequate in the light of current concepts of progesterone secretion in pregnancy (Zander, 1959) and inadequate control observations have invalidated much published data. To assess the salvage rate in treated pregnancies and then compare it with that found for previous untreated pregnancies in the same patients ignores the number of pregnancies that would have reached viability if no treatment had been given at all. Malpas (1938) produced a theoretical estimate that any woman with a history of three consecutive abortions. . .
PMID 13977012 13977012 DOI 10.1136/bmj.1.5326.292 10.1136/bmj.1.5326.292 Shearman et al. 1963, Shearman 1963
Cite this article
Shearman, R. P., & Garrett, W. J. (1963). Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate. British medical journal, 1(5326), 292-295. https://doi.org/10.1136/bmj.1.5326.292
Shearman RP, Garrett WJ. Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate. Br Med J. 1963;1(5326):292-295. doi:10.1136/bmj.1.5326.292
Shearman, RodneyP. P., and William J. Garrett. "Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate." British medical journal, vol. 1, no. 5326, 1963, pp. 292-295.
Porcaro G et al., 2015·European review for medical and pharmacological sciences
The clinic use of alpha Lipoic Acid (ALA) is linked to its capability to exert antioxidant effects and, more interestingly, to counteract the pathologic changes of complex networks of cytokines, chemokines and growth factors, restoring their physiological state. The aim of this randomized controlled clinical trial was to test the contribution of oral supplementation of ALA to the standard treatment with Progesterone vaginal suppositories, in healing subchorionic hematomas in patients with threatened miscarriage. Controls were administered only Progesterone suppositories. Nineteen pregnant women in the first trimester of gestation, with threatened miscarriage and ultrasound evidence of subchorionic hematoma, were included in the trial and randomly divided in two groups: controls, treated with 400 mg Progesterone (200 mg 2 times per day), given by vaginal suppositories, and case study treated with the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300 mg 2 times per day, DAV(R), Lo.Li. Pharma srl, Italy). Sixteen patients completed the trial. Treatment was performed until complete resolution of the clinical picture. In both groups, the subjects improved significantly but, in general, a better and faster evolution in the major signs of threatened miscarriage was observed in the subjects treated with ALA and Progesterone. In these patients, the speed of resorption of subchorionic hematoma was significantly (p <= 0.05) superior compared to controls. The ALA and Progesterone group showed a faster decrease or disappearance of all symptoms than that observed in the control group, however the difference was not significant. These preliminary results suggest that ALA supplementation significantly contributes to speed up the process of restoration of physiological conditions in threatened miscarriage and ameliorates the medical conditions of both the mothers and the foetus, probably modulating the networks of cytokines, growth factors and other molecules.
The plasma concentrations of medroxyprogesterone acetate (MPA) in 14 women administered the progestagen for threatened abortion during the first 6 weeks of pregnancy were measured by specific radioimmunoassay. Treatment (52 nmol orally every 6 h) was continued to 18 weeks of gestation. The mean plasma concentration of MPA rose rapidly during day 1 of treatment to 14.1 +/- 1.84 nmol/l. It reached 21.5 +/- 2.3 nmol/l by 7 days and subsequently stabilized at around 26.8 +/- 5.0 nmol/l by the end of week 2. Urinary steroid profiles were determined by gas-liquid chromatography and mass spectrometry for six of the MPA-treated women and compared with those of six untreated women of similar gestational age. No differences were detected between the two groups of women, suggesting that the administration of MPA during pregnancy did not alter qualitatively or quantitatively the metabolism and excretion into urine of progesterone and oestrogens.
Study of 54 habitual aborters with low or normal pregnanediol excretion, in a double-blind trial, revealed the spontaneous-salvage rate and the possible benefit of therapy with medroxyprogesterone acetate. The salvage rate in the placebo group with the worst prognosis (never a term pregnancy, low pregnanediol in the current pregnancy) was ten of 13, and the salvage rate in the other placebo groups showed no statistically significant difference. In view of this high spontaneous salvage rate, the numbers required to demonstrate a therapeutic effect of progestin administration are prohibitively large. This indicates the need for new criteria to pinpoint cases with a poor prognosis, and it raises the question whether habitual abortion is a disease entity or a statistical coincidence.
While investigating the use of progesterone for the relief of premenstrual syndrome (Greene and Dalton, 1953) a high incidence of toxaemia of pregnancy (19.1 %) was recognized among sufferers from this syndrome. A further investigation, undertaken to ascertain the incidence of premenstrual syndrome in those who had previously suffered from toxemia of pregnancy, revealed that 86% of the 237 women thus affected at one time or another during the previous twelve years also suffered from premenstrual syndrome (Dalton, 1954). Furthermore, direct questioning and a scrutiny of records of these patients showed that before the full development of the signs of toxaemia–that is, oedema, hypertension, and albuminuria–most had earlier in the pregnancy experienced a symptomatic stage characterized by relatively minor afflictions–for example, lethargy 43 %, headache 48%, visual aura 37%, vertigo 29%, nausea and vomiting 16%, irritability 14%, depression 9%, and backache 6%. In fact, only 7% disclosed freedom from these symptoms during a toxaemic pregnancy. Of the 237 women, 92 (38.8%) had experienced both a normal and a toxaemic pregnancy, and 72 (78 %) contrasted the sense of well-being associated with a normal pregnancy with the malaise and minor symptoms characteristic of the toxaemic condition. The striking feature of these early minor symptoms of toxaemia was their close resemblance to those of premenstrual syndrome noted in an earlier investigation (Greene and Dalton, 1953), most patients confirming that the minor symptoms during their toxaemic pregnancy were similar, though of increased severity, to those experienced in the premenstruum, irrespective of whether the onset of premenstrual syndrome had preceded or followed the toxaemic pregnancy. Apart from the similarities of these minor symptoms in the two conditions, other points in common were noted. For example, day-to-day observations of sufferers of premenstrual syndrome had shown that, apart from minor symptoms, some developed oedema, hypertension, and albuminuria during the premenstruum, with spontaneous improvement during menstruation. This appeared to be analogous to the spontaneous resolution of oedema, hypertension, and albuminuria following delivery. Furthermore, if symptoms remain untreated either in premenstrual syndrome or in toxaemia both diseases may culminate in fits, epileptic in the one case, eclamptic in the other. In an earlier investigation one of the reasons for using progesterone in the treatment of premenstrual syndrome had been that some patients suffering from this condition were symptom-free during pregnancy. It was considered that the corpus luteum and placenta supplied enough progesterone during pregnancy to keep these patients symptom-free. Others were not only unrelieved of their premenstrual symptoms during pregnancy, but, as already indicated, developed symptoms closely resembling those of the premenstruum and culminating in toxaemia. It was therefore thought possible that the development of toxaemia might in such cases arise from failure of the corpus luteum and placenta to produce sufficient progesterone. In the light of similarities between premenstrual syndrome and toxaemia, and the fact that treatment of the former with progesterone not only relieved the symptoms (Greene and Dalton, 1953) but also prevented the development of edema, hypertension, and albuminuria in the premenstruum (Dalton, 1954, 1955), it was decided to carry out a trial, employing large doses of progesterone in patients disclosing early minor symptoms of toxaemia, in an attempt to arrest full development of that condition.