A prospective controlled study of the impact of hyperthyroidism on reproductive function in males

The aim of this prospective controlled study was to ascertain the effect of hyperthyroidism on sperm quality and composition. We studied 23 thyrotoxic male patients, aged 43.8 ± 2.4 yr (mean ± SEM), and 15 healthy male controls of approximately the same age (42.2 ± 2.2 yr). Two semen analyses at intervals of 2-3 wk were obtained before and about 5 months after euthyroidism was achieved either by methimazole alone (14 patients) or 131I plus methimazole (9 patients). Total fructose, zinc (Zn), and magnesium (Mg) were also measured in seminal plasma in 16 patients, because 7 had semen volume less than 2 ml. In the control group semen analysis was performed only once. Mean (±SEM) semen volume was within normal range both in patients (3.3 ± 0.2 ml) and controls (3.5 ± 0.4 ml; P = NS). Mean sperm density was lower in patients, although the difference compared with controls did not reach statistical significance (35.7 ± 5.3 vs. 51.5 ± 6.1 × 106/ml; P = 0.062). The same was found with sperm morphology (68 ± 7% vs. 78 ± 8%; P = NS). Finally, mean motility was lower in thyrotoxic males than in controls (28 ± 8% vs. 57 ± 7%; P < 0.01). After treatment, sperm density and motility improved [35.7 ± 5.3 vs. 43.3 ± 6.5 × 106/ml (P = NS) and 28 ± 8% vs. 45 ± 7% (P < 0.05), respectively], but sperm morphology did not change (68 ± 7% vs. 70 ± 6%; P = NS). Mean values for fructose, Zn, and Mg did not differ between controls and patients either before or after achievement of euthyroidism [9.2 ± 0.7, 3.0 ± 0.5, and 4.2 ± 0.7 nmol/liter vs. 8.6 ± 0.9, 3.0 ± 0.5, and 4.7 ± 0.8 nmol/liter (patients before) and 9.1 ± 0.7, 3.1 ± 0.6, and 4.5 ± 0.9 nmol/liter (patients after treatment) for fructose, Zn, and Mg, respectively]. Moreover, according to the treatment given, no statistically significant differences were found before or after treatment. Finally, seminal plasma fructose, Zn, and Mg levels did not correlate with sperm parameters or with pretreatment thyroid hormone levels. In conclusion, the results of our study indicate that male patients with hyperthyroidism have abnormalities in seminal parameters, mainly sperm motility. These abnormalities improve or normalize when the patients become euthyroid. Restoration of sperm parameters was independent of the treatment provided for the hyperthyroid syndrome. Moreover, seminal plasma elements, such as fructose, Zn, and Mg, did not correlate with sperm density, motility, or morphology

Lanreotide in the treatment of patients with thyroid eye disease

Octreotide, a potent synthetic somatostatin (SM) analogue was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Fire patients , three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using In-111 DTPA-D-Phe(1)-octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The fire patients who comprised the treatment group received 0.04 g LRT i.m. once every 3 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to he given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results

MENSTRUAL DISTURBANCES IN THYROTOXICOSIS

OBJECTIVES In thyroid textbooks it is stated that hyperthyroidism in women may be associated in almost 50% of the cases with hypomenorrhoea, oligomenorrhoea or amenorrhoea and perhaps with reduced fertility. Our experience at a busy thyroid clinic has given a picture which differs from that described in the literature. Most of our female thyrotoxic patients had normal menstruation. This study was performed to define the menstrual abnormalities in hyperthyroidism. DESIGN AND PATIENTS We investigated the menstrual history, starting 6 months before the discovery of the disease, the smoking habits and the body mass index (BMI), in 214 female, premenopausal thyrotoxic patients and a similar number of normal controls matched for age and weight. MEASUREMENTS TT4 and TT3 were measured by radioimmunoassay, while BMI was calculated from the ratio of body weight in kg to height in m(2). RESULTS Of the 214 patients, 168 (78.5%) had regular menstrual cycles and 46 (21.5%) irregular cycles. No difference in BMI was found between the patients with or without menstrual abnormalities. Out of the 46 patients with irregular periods, 23 (50%) were smokers, while only 32 out of the 168 patients (19%) with normal periods were smokers (P < 0.001). TT4 levels were higher as a group in patients with menstrual disturbances (mean +/- SD 267.7 +/- 66.9 nmol/l) than in those with normal periods (240.6 +/- 47.6 nmol/l) (P < 0.05). The 23 smokers with irregular periods had higher TT4 levels (280.5 +/- 51.8 nmol/l) than the remaining non-smokers from the same group (241.9 +/- 43.7 nmol/l) (P < 0.01). No such differences were found for TT3 levels. Out of 214 normal controls, matched for age and weight, 196 (91.6%) had normal menstruation and 18 (8.4%) irregular cycles. The latter group included mainly women with oligomenorrhoea. Out of 18 normal controls with irregular periods, 6 (33.3%) were smokers, while 57 (29.1%) out of 196 with normal periods were smokers. CONCLUSIONS These data demonstrate that hyperthyroidism in women is less frequently associated with menstrual abnormalities than was previously believed. Furthermore, no patient presented with amenorrhoea. Smoking and TT4 levels are strongly associated with the occurrence of menstrual disturbances in thyrotoxicosis

Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS), A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system, The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS, Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections), GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min, The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (Delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUG 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and Delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml,P < 0.05), After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and Delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and Delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response, These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups, Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a, This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS

Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide

Leptin, a product of the ob gene, is a 16 kDa protein which is produced by adipocytes. In humans, obesity is a common finding in women with polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS is not clear Some studies have reported increased levels of leptin in PCOS, while others report that they are normal. Also, insulin resistance is a common finding in PCOS. The aim of this study was to investigate further the role of insulin in leptin secretion in patients with PCOS by treating them for 10 days with diazoxide, an insulin-reducing compound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean body mass index (BMI) 28.4 +/- 5.7 kg/m(2), were studied, An oral glucose tolerance test (OGTT) was performed in all women and blood samples were taken before and at 30, 60, 90, 120 and 150 min after the administration of glucose. Glucose, insulin, leptin, free testosterone, Delta 4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured in the sera taken before the administration of glucose, while glucose and insulin levels were measured in all samples which were collected after the administration of glucose. Diazoxide 300 mg daily was given to all women starting after the end of the OGTT for 10 days. A second OGTT was performed the day after the discontinuation of the diazoxide treatment. The same hormonal and biochemical parameters were also measured in all patients during the second OGTT. After the administration of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/- 341 mu U/ml, P < 0.01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml, P < 0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.3 pg/ml, P < 0.01), Delta 4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P < 0.01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P < 0.01) levels was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P < 0.01) and sum glucose leuels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/dl, P < 0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2.24 mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7 vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A significant positive correlation was found between serum leptin and BMI values before and after administration of diazoxide as well as between leptin, insulin and IGFBP-3 values. Also, sum insulin values correlated significantly with BMI. However, when multiple regression analysis was used this correlation was eliminated except that between leptin and BMI. This was most probably due to the small number of cases, The mechanism of the reduction of leptin levels is unclear, However, it is suggested that the concomitant decrease of insulin levels may play a role

Growth hormone response to thyrotrophin releasing hormone in women with polycystic ovarian syndrome

Recent clinical studies have suggested that women with polycystic ovarian syndrome (PCOS) may have disturbances of growth hormone (GH) kinetics and the GH/insulin-like growth factor (IGF)-I system. The knowledge that in various metabolic abnormalities there is a paradoxical sensitivity of pituitary somatotrophs to thyrotrophin-releasing hormone (TRH) administration led to this investigation of the GH secretory response to TRH in women with PCOS, Twenty-four women with PCOS and 18 control women were studied. TRH was given as a single i.v. injection (time 0) and blood samples for GH measurements were obtained at -15, 0, 15, 30, 60 and 90 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (Delta max), The GH response to TRH(mean +/- SEM) was greater in women with PCOS (Delta max 2.47 +/- 1.73 versus 0.47 +/- 0.06 ng/ml, P < 0.05 and GH AUC 8.05 +/- 2.10 versus 2.58 +/- 0.18 ng/ ml/90 min, P < 0.05), According to GH response to TRH, two PCOS subgroups were identified: (i) normal responders (n = 14) who showed Delta max GH response (0.36 +/- 0.06 ng/ml)and GH AUC (1.93 +/- 0.64 ng/ml/90 min) similar to that in the controls and (ii) over-responders (n +/- 10) who showed a paradoxical increase in GH concentrations in response to TRH Delta max GH response 5.43 +/- 1.27 ng/ml and GH AUC 16.62 +/- 3.51 ng/ml per 90 min) that was significantly higher than in normally responding PCOS patients (P < 0.0001) or in controls (P < 0.0001), These data demonstrate an enhanced GH response to TRH administration in a subgroup of women with PCOS