Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.      

Immunological findings in anorexia and bulimia nervosa

Cytofluorometric studies, using monoclonal antibodies directed against surface antigens of mononuclear blood cells, were conducted in 10 patients with anorexia nervosa, 12 patients with bulimia nervosa, and in 9 healthy, age matched controls. While total leukocytes were not different between groups, the number of lymphocytes was significantly reduced in anorectic but not in bulimic patients. The number of T- but not of B-lymphocytes and monocytes/macrophages was diminished. All T-cell populations (helper/inducer = CD4); suppressor/cytotoxic = CD8) and CD57 positive natural killer (NK) cells were reduced in anorexia nervosa. This effect is probably caused by increased glucocorticoid secretion.     

Assessment of body composition by measurement of electrical conductivity in patients with anorexia nervosa and bulimia

Body composition was measured by electrical conductivity in 7 anorexic, 10 bulimic, and 14 control subjects. Potassium 40 measurement was used as a reference method. Percent fat calculated from both measurements correlated highly (r_s = + 0.89, p<.001). The precision of the electrical conductivity method was studied and shown to be satisfactory in three anorexic patients and two controls.     

Altered insulin response to a balanced test meal in bulimic patients

Impaired glucose tolerance with overshooting insulin secretion has been reported in anorexia nervosa, in starvation, and in low carbohydrate diets. Since impaired glucose tolerance is a further indicator of starvation andlor carbohydrate restriction and possibly contributes to impairment of mechanisms of hunger and satiety, we examined insulin and glucose responses in bulimic patients. Data show that in bulimic patients as compared with age-matched controls, insulin secretion and glucose levels can be elevated after a balanced test meal. This indicates disturbed glucose tolerance. Whether this reduced glucose tolerance can be related to altered kinetics of insulin release or to cellular insulin resistance cannot be decided on the basis of our data.     

Effects of testosterone replacement on sexual behavior in hypogonadal men

Fifteen patients with hypogonadism due to testicular, pituitary, or hypothalamic failure were studied. After a pretreatment period without substitution, patients received intramuscular injections of testosterone enanthate, equivalent to 25, 50, 100, and 250 mg testosterone, or placebo. Each dose was given for 4 weeks, with injections given every 2 weeks. All patients with plasma testosterone values below 2 ng/ml during the pretreatment period reported impaired sexual function. They responded to testosterone injections (50, 100, and 250 mg) with improvement of sexual behavior, as rated by sexual desire and frequency of erections and ejaculations. In the range between 2.0 and 4.5 ng testosterone per ml, four patients reported high frequencies of erections and ejaculations that did not change after testosterone treatment. Four other patients with testosterone values in the same range reported impaired sexual behavior and were successfully treated with testosterone enanthate. These data indicate that male sexual behavior is testosterone dependent and that the individual limit of plasma testosterone below which sexual behavior is impaired lies between 2.0 and 4.5 ng/ml.     

Effect of dexfenfluramine on sleep in healthy subjects

The acute effects of dexfenfluramine on nocturnal sleep were studied in ten healthy male subjects by means of sleep EEG recordings and ratings of subjective sleep quality. Four different dosages (3 mg, 7 mg, 15 mg, and 30 mg) were tested, administered over a period of 3 days each. Under 15 mg and 30 mg dexfenfluramine, only slight effects on sleep were observed: 15 mg led to decreased sleep efficiency in the first night of medication, and to reduced percentage of slow wave sleep in the first and third night. A significant lengthening of REM latency was present in the third night under 30 mg dexfenfluramine, without changes in other REM sleep parameters. Daily doses of 3 mg and 7 mg dexfenfluramine did not influence sleep, except for a significant REM latency reduction observed in the first night under 3 mg. Apart from a transient slight impairment under 30 mg, ratings of subjective sleep quality did not mirror any impact of dexfenfluramine. The data suggest that therapeutic dosages of dexfenfluramine only slightly influence nocturnal sleep, which contrasts with the known impact of other anti-obesity agents like the amphetamines. Unlike classical antidepressants, dexfenfluramine does not reduce REM sleep; in light of a hypothetical link between REM sleep reduction and antidepressant action of a drug, dexfenfluramine is not expected to have a pronounced antidepressant effect.     

Cranial computed tomography findings in bulimia

In cranial computed tomography (CT), not only patients with anorexia nervosa but also patients suffering from bulimia, display enlarged external cerebrospinal fluid spaces. This was true for more than one third of the 28 bulimic patients studied, regardless of whether or not they had a past history of anorexia nervosa. As the bulimic patients had a near normal body weight, the observed structural changes cannot be attributed to underweight, as is commonly assumed to be the case in anorectic patients. These findings indicate that, in addition to underweight, other factors have to be considered as causing the morphological brain alterations present in patients with eating disorders.