Uterine contractility: vaginal administration of the beta-adrenergic agonist, terbutaline. Evidence of direct vagina-to-uterus transport.

Spontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina-to-uterus transport of administered compounds (i.e., the "first uterine pass effect"). It is possible that treatment with uterorelaxing substances, particularly beta-adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of beta-agonists limit their utility. Alternatively, vaginal delivery of beta-agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina-to-uterus transport of [3H]terbutaline, a well-known beta-agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.

The hormonal control of endometrial receptivity: estrogen (E2) and progesterone.

While the number of identified substances produced by the ovary increases steadily, it remains remarkable that the sole use of exogenous estrogen (E2) and progesterone (P) can prime optimal endometrial receptivity in women whose ovaries have failed or are absent. Early work showed that a marked leeway existed in the acceptable duration of the E2-only phase of endometrial priming. Subsequently, a sequence of transformations are induced by exogenous progesterone that reproduces classical findings made in the menstrual cycle. Secretory changes in endometrial glands are best seen between the 4th and 6th day of progesterone administration (day 18-20 of an ideal cycle where progesterone exposure starts on day 15). Predecidual changes of the endometrial stroma are apparent starting on the 10th day of progesterone exposure (day 24). Contrary to earlier belief, even maximal alterations in the plasma E2 to progesterone ratio fails to alter the endometrial morphology of either glands or stroma. More recently it has been recognized that E2 and progesterone also affect uterine contractility. It has been postulated that excessively high levels of E2 may increase uterine contractility and adversely affect implantation rates in in-vitro fertilization (IVF). Exogenous progesterone has been shown to exert utero-relaxing effects and it has been hypothesised that progesterone supplementation before embryo transfer (ET) may improve receptivity in IVF.

The influence of nicardipine in type 2 diabetic patients with slight hypertension.

A double-blind, placebo-controlled study was carried out over 120 days to assess the metabolic tolerance and patient acceptability of nicardipine in 20 patients with Type 2 diabetes mellitus and slight hypertension. Following a 21-day washout period during which all patients received placebo, 13 men and 7 women (mean age 45 years, systolic blood pressure 150-165 mm Hg or diastolic blood pressure 85-100 mm Hg) were randomly assigned to treatment with oral nicardipine 60-90 mg/day (n = 9) or placebo (n = 11). No significant differences were observed between the nicardipine- and placebo-treated groups in terms of fasting and postprandial blood glucose concentrations, fasting plasma insulin levels, or glycosylated hemoglobin A1c after 60 and 120 days' treatment. There was also no change in the plasma levels of total cholesterol, HDL-cholesterol, triglycerides, and apolipoproteins. Side effects were minor and did not differ significantly between groups. All patients who had received nicardipine for 120 days wished to pursue treatment. Nicardipine, which was well tolerated, appears to be an interesting alternative for the treatment of mild essential hypertension in Type 2 diabetic patients, although further studies are required to establish its effects on renal function in this population.

Comparative metabolic study of percutaneous versus oral micronized 17 beta-oestradiol in replacement therapy.

The aim of this study was to compare the metabolic effects of two presentations of 17 beta-oestradiol (E2) which are of recognized effectiveness in the prevention of post-menopausal bone loss, one being administered via the oral and the other via the percutaneous route. During this prospective, randomized study, 32 patients were treated for 2 mth with either 2 mg/day of oral micronized E2 (n = 16) or 1.5-3 mg/day of percutaneous E2 (n = 16). Both regimens proved efficacious, since significant increases in oestrone (E1) and E2 concentrations ranging up to mid-follicular values were observed. In the percutaneous-treatment group we noted a significant decrease in triglycerides (TG), without any significant changes in high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). In the oral-treatment group, we saw no significant increase in HDL-C, although significant increases were observed in body weight, TG, plasma renin substrate (PRS) and sex-hormone-binding globulin (SHBG) as well as significant decreases in antithrombin III (AT III) activity and antigen. All of these metabolic variations led us to the conclusion that oral E2 at the dose established as effective in preventing post-menopausal osteoporosis may, even when micronized, alter certain metabolic and haemostatic parameters in a population characterized by increases in cardiovascular risk factors and morbidity. Oral oestrogen replacement therapy should therefore continue to be used only in carefully selected patients and be strictly followed up by systematic checks on a series of metabolic criteria.

[Auto-immune hypoglycemic syndrome induced by pyritinol]. / Syndrome hypoglycémique auto-immun induit par le pyritinol.

The auto-immune hypoglycemic syndrome is characterized by the association of hypoglycemia (clinical and/or biological) and anti-insulin antibodies in patients who have never received exogenous insulin. Initially this syndrome was most often described in Japanese patients some of whom were treated with drugs containing a sulfydril group. We now recall the case of a female caucasian patient treated with Pyritinol for rhumatoid polyarthritis and who presented severe spontaneous hypoglycemia linked with the presence of anti-insulin antibodies in her serum. The level of her antibodies decreased abruptly on suspension of the drug. The recent and more developed characterization techniques of the different forms of circulating insulin and of their antibodies may help to differenciate an auto-immune hypoglycemia from hypoglycemia due to the secret auto-administration of bovine and porcine insuline, and permit us to suggest that an abnormality in the structure of the molecule of insulin might be a cause of this syndrome. However, the exact mechanism of hypoglycemia linked with the presence of anti-insulin auto-antibodies is not yet clear as is the predisposition of a drug with a sulfydril group to induce such an auto-immune phenomenon.