Patrick Sharp

DIFFERENCES IN CLINICAL AND ENDOCRINE FEATURES BETWEEN OBESE AND NON‐OBESE SUBJECTS WITH POLYCYSTIC OVARY SYNDROME: AN ANALYSIS OF 263 CONSECUTIVE CASES

Two hundred and sixty‐three women with ultrasound‐diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI > 25 kg/m2‐). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non‐obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5α‐reductase activity, were higher in obese than in non‐obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8‐h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio‐availability of androgens to peripheral tissues and enhanced activity of 5α‐reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Replacement treatment with biosynthetic human growth hormone in growth hormone‐deficient hypopituitary adults

OBJECTIVES The physiological role Of growth hormone in adult life has recently attracted increased Interest. We have studied the clinical effects and the effects on body composition of prolonged replacement with biosynthetic human GH In a large number of hypopituitary adults. DESIGN A randomized double blind placebo controlled trial for 6 months followed by an open trial of GH treatment for 12 months. GH dally dose was 0·04 (0·02‐0·05) IU/kg s.c.

Correlation of plasma insulin and insulin‐like growth factor‐I with indices of androgen transport and metabolism in women with polycystic ovary syndrome

Summary. objective Polycystic ovary syndrome (PCOS) Is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of Insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen trans‐port and metabolism In women with PCOS.

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism

OBJECTIVE The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with blosynthetic human GH in hypopituitary adults on aspects of calcium homeostatis, bone metabolism and bone mineral mass.

Obesity and polycystic ovary syndrome.

Our studies show that obese women with polycystic ovary syndrome are more likely to have hirsutism and menstrual disturbances than are lean women with PCOS. The most obvious biochemical differences between obese and lean women with PCOS is that SHBG concentrations are much lower in women with obesity. The SHBG levels are inversely related to insulin, and insulin has been shown to have a direct inhibitory action on SHBG secretion. Other factors, however, may contribute to the mechanism of the increased prevalence of hirsutism and anovulation in obese women with PCOS, such as a direct effect of insulin or increased activity of 5 alpha-reductase in peripheral tissues. Finally we have been able to show that weight reduction of more than 5% is associated with an improved biochemical profile and, importantly, with restoration of fertility.

The role of nutrition and insulin in the regulation of sex hormone binding globulin

In an analysis of 263 women with polycystic ovary syndrome (PCOS), 91 (35%) of whom were obese (body mass index greater than 25 kg/m2), it was found that obese women with PCOS were more likely to be anovulatory and had a higher prevalence of hirsutism than the non-obese subgroup. Although serum concentrations of gonadotrophins, androstenedione and total testosterone were similar in obese and lean women with PCO, sex hormone binding globulin (SHBG) levels were significantly lower, and free testosterone correspondingly higher, in obese women. Serum concentrations of SHBG were inversely correlated with those of both fasting and glucose-stimulated insulin. A short-term, very-low-calorie diet resulted in a 2-fold increase in SHBG which was mirrored by a fall in serum insulin. Similar biochemical changes were also observed during a long-term (6-7 months) 1000 kcal diet and were associated with an improvement of menstrual function and fertility. This encourages the view that calorie restriction has an important part to play in the management of obese women with PCOS.

Psychiatric morbidity in adults with hypopituitarism.

Forty-one adults with established hypopituitarism and deficiency of growth hormone (GHD) were compared to an age and sex-matched group with another chronic metabolic disorder (diabetes mellitus) using standardized psychiatric rating and diagnostic measures. Nineteen (46%) of the GHD group were identified as definite psychiatric cases compared with 10 (24%) of the diabetics (odds ratio 1:9:1). The most frequent DSM III-R axis I psychiatric diagnoses were major depression (32% GHD patients and 10% of diabetic patients) and dysthymia. The risk of being a psychiatric case showed an association with duration of illness in the diabetic group, but not in the GHD group. Biochemical indices were not related to the risk of being a case in either group. Hypopituitarism is associated with a higher prevalence of psychiatric disturbance than can be attributed solely to the presence of a chronic disorder.

The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh

To investigate whether growth hormone (GH) absorption is site dependent.

Metabolic Changes and Vascular Risk Factors in Hypopituitarism

Adults with hypopituitarism die prematurely, and the excess mortality is from vascular disease. On echocardiography we have demonstrated abnormalities of myocardial diastolic function in hypopituitary adults, indicating possible early ischaemic change. Peripheral arterial disease is evident on ultrasonography. Vascular risk factors have also been examined. Impaired glucose tolerance and unrecognized diabetes are common in hypopituitary adults. Total cholesterol levels are elevated, particularly in hypopituitary women. The role of growth hormone (GH) deficiency in the vascular disease and in the vascular-risk-factor abnormalities is unknown at present. Prolonged GH therapy causes a decrease in the levels of fasting total cholesterol, without any adverse effects on glucose homeostasis. GH therapy trials in adults will clarify the role of GH in the excess vascular risk of hypopituitarism. Prolonged GH therapy will be necessary for the vascular effects to be defined.