Premenstrual syndrome.

The term premenstrual syndrome is often used to describe several clinical conditions. Only a full history covering not only reproductive but also psychological and social factors, combined with daily diaries which are kept prospectively for at least two months, can help clarify the problems the patient experiences. As it is the timing rather than the type of symptoms which is essential to a diagnosis, diaries are used to assess symptoms, make a diagnosis and monitor the effectiveness of therapy. Patients with premenstrual syndrome should therefore always keep a diary and bring it to every consultation. We do not know if patients complaining of premenstrual syndrome are at one extreme of a spectrum disorder or if they are a 'specific group'. Such patients may have classical premenstrual syndrome, perimenstrual distress, benign idiopathic oedema, dysmenorrhoea, cyclical benign breast disease or mood symptoms which are not significantly related to the menstrual cycle. There are many aetiological theories--biological, psychological, environmental and social, the syndrome being a complex psychosomatic disorder. For appropriate management an accurate diagnostic formation is required. Reassurance, stress management techniques, an improvement in general mental and physical well-being, information and education are the mainstays of therapy. Symptomatic relief of symptoms is often helpful. Many other managements have been tried with the aim of correcting the underlying aetiological case. These include vitamins, prostaglandin inhibitors and endocrine therapies. As the disorder is long-term, the safety of treatments should be carefully considered.

Premenstrual syndrome. A double-blind cross-over study of treatment with dydrogesterone and placebo.

A double-blind, cross-over, placebo-controlled study of dydrogesterone (10 mg b.d.) in the treatment of premenstrual syndrome is described. Two groups of women were studied: secondarily referred hospital clinic patients, and self-referred patients. Only one-third of patients screened completed the study. All patients showed significant improvements in symptom scores during the course of the study, the only significant difference between placebo- and dydrogesterone-treated patients being an increase in frequency of breast tenderness and a decrease in pain with menstrual bleeding in the latter.

The assessment of the symptoms of premenstrual syndrome and their response to therapy.

The symptoms of premenstrual syndrome should be rated daily, or at frequent intervals throughout the menstrual cycle. Self-rating is usually most feasible and separate rating of differing symptom groups is important, as symptoms differ in their response to therapy. Daily scores should be analysed to assess periodicity, either by subdividing the cycle into phases or by using the least mean square method of fitting sine waves. Standardized scores enable data to be compared across cycles. In a clinical trial it is important to include an untreated cycle to assess whether the subject has premenstrual syndrome and as a baseline with which to compare treated cycles. Allowance should be made for a carry-over effect and for high placebo response. One solution is to use a change-over design balanced for carry-over effects. The criteria used to define a patient should be stated.

Urinary dicarboxylic acids in patients receiving lithium or rubidium salts.

Lithium salts administered in therapeutic doses to four subjects who were kept on controlled diets increased up to fivefold the urinary output of some dicarboxylic acids. Some of the acids affected are intermediates in the tricarboxylic acid cycle, others are chemically similar but not directly related in metabolic terms. This is probably a direct effect on renal transport. Rubidium salts increased urinary 2-oxoglutarate output and blood 2-oxoglutarate levels, probably by some action on intermediary metabolism.

Premenstrual syndrome: a double-blind controlled trial of progesterone and placebo.

Patients with premenstrual syndrome recorded their symptoms daily using menstrual distress questionnaires. These were analysed by a least mean square method of fitting sine waves. After recording an untreated cycle, patients were given progesterone 200 mg b.d. and placebo in a double-blind crossover manner; 75 per cent of patients were then given progesterone 400 mg b.d. and placebo in a similar manner. Treated cycles were rated by both daily menstrual distress questionnaires and retrospective self-assessment. Both rating methods showed there was no significant difference between progesterone and placebo in reducing symptoms of premenstrual syndrome, and in the majority of cases placebo was more effective, although never significantly so.

Oestradiol secretion in men and pre-menopausal women.

Blood samples were obtained from a group of regularly-cycling normal women (n = 13) and a group of normal men (n = 5) at 15 min intervals for periods ranging from 9-14 h whilst the subjects remained resting quietly in bed. The concentration of plasma oestradiol was measured in a radioimmunoassay which had been carefully optimised and the mean concentration and coefficient of variation calculated for each subject. Plasma oestradiol concentrations were found to fluctuate rapidly in all subjects. The largest sample-to-sample variation was found in regularly cycling women near mid-cycle, and the least variation occurred in the male subjects. The coefficients of variation were approximately twice the intra-assay variation confirming that the observed pulsatile patterns of secretion were not due to technical errors. An analysis of variance performed on the mean hourly concentrations from each subject showed a significant variation (P less than 0.001) between sampling periods with peaks occurring during the first hour of sampling (08.00-09.00 hours). This result is suggestive of the presence of a circadian rhythm although it is not conslusive.

Studies of daily recordings from the Moos Menstrual Distress Questionnaire.

Nineteen volunteers completed a Moos Menstrual Distress Questionnaire daily for a period exceeding one menstrual cycle. The data were analysed, using a least mean square method of fitting sine waves. The fact that the results obtained on this group are essentially those found by other workers looking at the menstrual cycle suggests that this may be a useful method for assessing menstrual distress.

The effect of lithium salts on the urinary excretion of -oxoglutarate in man.

1. Lithium ions in therapeutic doses cause an increase in the renal excretion of alpha-oxoglutarate and glutaric acid.2. The excretion is probably due to reduced renal tubular reabsorption.3. Neither citrate, lactate nor pyruvate excretion rises.