Progesterone and the premenstrual syndrome: a double blind crossover trial.

Abstract

complication it might be difficult to conclude which was the most significant risk factor for death. None the less, overall case fatality rate was highest among children with hyponatraemia.The multiple linear regression model showed that deaths associated with hyponatraemia, hyperkalaemia, and hypoglycaemia were significant at the 010 confidence level, but the effect of confounding factors could not be measured.In the logit regression model, which measures the effect of confounding factors, all the variables except serum sodium concentration and coma lost their effects. This observation that death was inversely related to serum sodium concentration supports our earlier findings that hyponatraemia is the most significant risk factor among children with complicated diarrhoea in Bangladesh.4 We reported earlier that the incidence of hyponatraemia was directly related to the degree of malnutrition, but the results of the logit regression analysis did not show that malnutrition was a significant predictor of death. The reason for the direct relation of the incidence of hyponatraemia to the degree of malnutrition might be that serum albumin concentration carries a negative charge and is largely responsible for the normal anion gap by holding serum sodium in the intravascular space.'0 11 Although nutritional state was not found to be a predictor of death, the serum albumin concentration in these children was not run as a variable in the logit regression model owing to lack of data. None the less, hyponatraemia remained a significant predictor of death, though we do not have any satisfactory explanation for this. The direct relation between the incidence of hyponatraemia and the degree of malnutrition necessitates further, prospective studies to assess the effect of serum albumin concentration on the physiopathology of hyponatraemia.The finding of coma as a predictor of death was not expected. As postmortem examinations were not performed we are unable to discuss the cause of the coma and its relation to death. Progesterone and the premenstrual syndrome: a double blind crossover trial L DENNERSTEIN, C SPENCER-GARDNER, G GOTTS, J B BROWN, M A SMITH, G D BURROWS Abstract A double blind, randomised, crossover trial of oral micronised progesterone (two months) and placebo (two months) was conducted to determine whether progesterone alleviated premenstrual complaints. Twenty three women were interviewed premenstrually before treatment and in each month of treatment.

Withdrawal from 3α-OH-5α-Pregnan-20-One Using a Pseudopregnancy Model Alters the Kinetics of Hippocampal GABAA-Gated Current and Increases the GABAAReceptor α4 Subunit in Association with Increased Anxiety

“…These effects were correlated with significant increases in hippocampal levels of the ␣4 subunit of the GABA A receptor, a possible mechanism for the observed neurosteroid withdrawal effects. Use of the pseudopregnant model here may have application for increased emotional lability and altered BDZ response reported for the premenstrual and postpartum periods (Dennerstein et al, 1985;Sundstrom et al, 1997). In addition, increased CNS levels of 3␣,5␣-THP have been noted during periods of chronic stress in male rats (Purdy et al, 1991), suggesting that 3␣,5␣-THP withdrawal may also arise in association with stressful episodes in both sexes.…”

“…The use of a pseudopregnancy model here provided several advantages over use of single or multiple injection or chronic implant, as reported earlier: (1) it is a more physiological paradigm than the other procedures, because progesterone is produced by an endogenous, ovarian source; (2) the time course of progesterone exposure, with progesterone elevated from day 4 to 12, is similar to progesterone exposure during the luteal phase of the menstrual cycle (Dennerstein et al, 1985;Rapkin et al, 1997), thus making this a usef ul model for PMS and postpartum conditions; (3) not only are progesterone and 3␣,5␣-THP released, but a number of other steroids are also naturally released by the ovary and corpus luteum, also making this a better in vivo model (Robinson et al, 1981;K im and Greenwald, 1986); (4) release of progesterone under physiological states, such as estrus, pregnancy, and pseudopregnancy is somewhat episodic (Robinson et al, 1981;K im and Greenwald, 1986), a phenomenon that could not easily be replicated by artificial means of administration. The fact that hormone release is episodic in this model may explain why a single withdrawal cycle was effective in the present study in triggering withdrawal properties, whereas in earlier studies, multiple withdrawal cycles were required (Costa et al, 1995;Smith et al, 1998).…”

Regulation of GABAAReceptor Subunit Expression by Pharmacological Agents

“…Therefore, exogenous neurosteroids also up-regulate ␣4␤␦ receptors and increase tonic inhibition. Discontinuation of administration of a neurosteroid agonist or the parent compound progesterone (i.e., withdrawal) leads to a 3-fold increase in hippocampal ␣4 and ␦ (but no change in ␥2 expression) (Smith et al, 1998;Sundstrom-Poromaa et al, 2002;Gangisetty and Reddy, 2009) and in premenstrual syndrome-like symptoms such as anxiety and increased seizure susceptibility (Dennerstein et al, 1985;Herzog, 2009).…”

Nongenomic Steroid Action: Controversies, Questions, and Answers

“…During one of the few controlled, double-blind studies, progesterone was shown to improve many symptoms of women suffering from premenstrual syndrome (116), including alleviation of depression. Because progesterone is metabolized to many different neuroactive steroids, it is difficult to determine which hormone(s) ultimately confer the effect.…”