Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.

UNLABELLED: AIM. To elucidate the dynamics of FSH, LH, prolactin (PRL), TSH and insulin secretion in women with polycystic ovarian syndrome (PCOS) treated with metformin (MET). PATIENTS AND METHODS: In a prospective, controlled and randomised trial, 32 women with PCOS and 32 with normal cycle were recruited to receive MET (850 mg b.i.d.) or placebo (n: 16 for each subgroup) for an average of 40 days. Pituitary function and insulin secretion were assessed before and after intervention by GnRH-TRH tests and oral glucose tolerance test induced insulin response. RESULTS: Basal and area under the response curve (AURC) LH values were higher in PCOS than in normal controls before MET and declined following treatment in the former group (P < 0.05). Ovulatory PCOS responders had lower basal LH, AURC(LH) and AURC(PRL) values during MET than anovulatory cases (P < 0.05 for all) and AURCins was lower in ovulatory than anovulatory PCOS before and on MET (P < 0.02-P < 0.05), with a rise of QUICKY index in the former group during MET treatment (P < 0.05). FSH and TSH were similar. CONCLUSIONS: MET administration lowered LH activity in all PCOS women and in ovulatory responders and also compromised PRL stimulated secretion in the latter cases. These findings were indicative of an effect of MET on pituitary activity.

Divergent Patterns of Thyrotropin and Other Thyroidal Parameters in Relationship with the Sex of Healthy Neonates and Infants Less than Two Years Old: A Longitudinal Study.

Background: A longitudinal study was conducted in full-term healthy infants who were born between 2015 and 2017 in Athens, Greece, to elucidate the evolution of thyrotropin (TSH) and other thyroidal parameters according to sex, from their day of birth until two years old. Other thyroidal parameters that were taken into account include antithyroid peroxidase antibody (TPO-Ab) and antithyroglobulin antibody (TG-Ab), total triiodothyronine (T3), and free triiodothyronine (fT3), along with total thyroxine (T4) and free thyroxine (fT4). Methods: Blood samples were taken at 5-day intervals from the day of birth until the 31st day of life, and then every 5th month until 2 years of age. All thyroid parameters were measured by electrochemiluminescence immunoassays. The study took place at the Iaso General, Maternity and Gynecological Clinic in Athens, Greece. Results: The sample consisted of 2916 full-term healthy neonates/infants: 1507 (51.7%) boys and 1409 (48.3%) girls. There were no significant differences in TSH levels between boys and girls in all time periods from birth up to 2 years except between 11 and 15 months of age (p = 0.038). Mean TSH levels for boys exhibited much more fluctuation and variability than for girls. In boys we found a significant association between TSH levels and fT4 (p < 0.001), while we found a significant association between TSH levels and T3 in girls (p = 0.045). Furthermore, we found that mean TPO-Ab and TG-Ab levels for boys exhibited larger variability than those for girls. Conclusions: In this study, we were able to plot the development of TSH and other thyroidal parameters by sex from birth up to two years of age. In terms of clinical practice, our findings suggest the need for a re-evaluation of the reference ranges of the studied parameters according to sex, especially in the first months of life and until the first year. Furthermore, our results suggest new optimal ranges for thyroid hormone replacement for that specific period.

Comparison of Triflusal with Aspirin in the Secondary Prevention of Atherothrombotic Events; Α Randomised Clinical Trial.

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

Association of carotene rich diet with hypogonadism in a male athlete.

AIM: To report on a unique case of hypogonadism associated with excessive carotene intake in a young male athlete. CASE REPORT: A 20-year-old patient presented with a gradual decline in muscular and physical activity, sexual interest and erectile ability associated with a high in carotene and low in animal fat diet of his own design a year prior to the clinical manifestations. Clinically, he presented with very overt signs of carotene excess: his palms and soles were yellow. Moreover, 2 weeks after normalization of his diet, carotene B levels were at the upper end of the normal range. METHODS: Repeated stimulation tests of hypothalamic, pituitary and testicular function were performed before and at 3, 6 and 12 months after the introduction of a balanced diet. RESULTS: Very low basal and stimulated values for gonadotropins and gonadal steroids were found at the initial evaluation with a progressive recovery shown after months of a balanced diet and carotene B restoration. Complete androgen secretion and sexual response recovery were observed only after 9-12 months from diagnosis. CONCLUSION: This is the first report associating excessive carotene intake with a hypothalamic form of hypogonadism in a young man.

Age at menopause and prevalence of its different types in contemporary Greek women.

OBJECTIVE: This study attempted to estimate the mean age at menopause and also characterize and quantify its types and frequencies in Greek women who have recently become postmenopausal. DESIGN: A retrospective analysis of hospital records was used to record the frequency of natural, spontaneous or induced premature, and delayed natural menopause; the mean age at menopause of each group; and their possible interrelationships with major events of reproductive history in 1,747 women visiting an endocrine clinic 1 to 5 years after menopause. A group of 438 postmenopausal women drawn from 4,000 cases from the nongynecological clinics of this hospital comprised the control group. RESULTS: Natural menopause was found in 1,333 (76.3%) women with a median age of 51 (95% CI, 50.8-51.2) and mean +/- SD of 48.7 +/- 3.8 years. Medically induced menopause after the age of 40 was recorded in 204 women (11.7%), spontaneous premature in 127 (7.1%), medically induced premature in 60 (3.7%), and delayed menopause in 26 (1.5%), with mean ages of 43.6 +/- 1.7, 35.1 +/- 3.3, 37.2 +/- 1.6, and 59.6 +/- 2.1 years, respectively. No significant differences in mean age at menopause or its types were noted between the two groups. Furthermore, no significant correlations among the parameters examined could be demonstrated except between smoking and age at menopause in the spontaneous premature menopause subgroup (P < 0.05). Finally, ovarian autoantibodies were found in 6.7% of the tested women with premature menopause. CONCLUSIONS: Natural menopause occurred at a mean age of 48.7 years in Greek women, who displayed an unexpectedly high prevalence of spontaneous or induced premature cessation of menstruation.

Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia.

OBJECTIVE: To assess the effect of treatment with a combination of the antiestrogen tamoxifen citrate and the androgen testosterone undecanoate on sperm variables and pregnancy incidence in men with idiopathic oligozoospermia and couple subfertility. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: Clinical research in a tertiary care academic hospital. PATIENT(S): Two hundred twelve men with idiopathic oligozoospermia and 82 normozoospermic men with female factor subfertility. INTERVENTION(S): Oligozoospermic patients were randomly assigned to two treatment groups with tamoxifen citrate, 20 mg/d, and testosterone undecanoate, 120 mg/d (n = 106) or placebo treatment (n = 106) for 6 months. Normozoospermic men were followed for the same period. Couple counseling was part of the intervention in all groups. MAIN OUTCOME MEASURE(S): Pregnancy incidence and sperm characteristics after 3 and 6 months on medication and 3 months after the end of the trial. RESULT(S): In the active treatment group, total sperm count (median [25th, 75th percentile], 27.1 x 10(6) cells/mL [9.4, 54.0 x 10(6) cells/mL] at baseline and 61.5 x 10(6) cells/mL [28.2, 119.6 x 10(6) cells/mL] at 6 months), progressive motility (mean [+/-SD], 29.7% +/- 12.0% at baseline and 41.6% +/- 13.1% at 6 months), and normal morphology (mean, 41.2% +/- 14.0% at baseline and 56.6% +/- 11.5% at 6 months) were noted. No marked changes were observed in placebo recipients or normozoospermic men. The incidence of spontaneous pregnancy was 33.9% in the active treatment group and 10.3% in the placebo group (36 vs. 11 pregnancies), with a relative risk of 3.195 (95% CI, 2.615 to 3.765). CONCLUSION(S): Treatment with tamoxifen citrate and testosterone undecanoate improved sperm variables and led to a higher incidence of pregnancy in couples with subfertility related to idiopathic oligozoospermia.

Body mass index vis-à-vis total sperm count in attendees of a single andrology clinic.

In this large series of 349 unselected men, no significant relationship between body mass index and total sperm count was found. Thus, the association of body mass index and sperm count reported in some studies was not confirmed.

Assessment of Sertoli cell functional reserve and its relationship to sperm parameters.

Sertoli cell functional reserve was assessed in normozoospermic men and oligozoospermic patients and its prognostic potential was evaluated for patient selection and treatment. For the first objective, three groups of normo-follicle-stimulating hormone (FSH)/normozoospermic fertile men (n:12), normo-FSH/oligozoospermic (n:21) and hyper-FSH/oligozoospermic subfertile men participated in the study whereas for the second objective 24 normo-FSH oligozoospermic patients volunteered for a pilot therapeutic trial. For the first part, high purity (hp) FSH (225 i.u., i.m.), human chorionic gonadotropin (hCG) (1500 i.u., i.m.) or their combination was given separately at weekly intervals, with samplings at 0, 3, 24 and 48 h. For the pilot trial, rec-FSH (150 i.u./48 h, i.m.) or placebo were prescribed for 6 months. The main outcome measures for the study were inhibin-B (inh-B), insulin-like growth factor (IGF)-I, testosterone and oestradiol concentrations and the main sperm parameters. Bolus administration of hp-FSH or hp-FSH/hCG combination in normozoospermic men resulted in a significant rise of inh-B in normozoospermic men (mean +/- SD, basal: 183.8+/-24.2 pg/mL in hp-FSH and 175.2+/-23.5 in hp-FSH/hCG treatment; 48 h: 256.1+/-34.2 and 246.3+/-19.0, respectively, p<0.001 for both). In oligozoospermic groups basal inh-B concentration was lower than in normozoospermic men (normo-FSH: 117.4+/-16.5, hyper-FSH: 81.2+/-19.8, p<0.001 for both) with a post-stimulation increase noted only in normo-FSH patients (hp-FSH 24-h: 132.8+/-19.7, p<0.01; hp-FSH/hCG 0 min: 105.7+/-20.1, 24-h: 119.5+/-20.6, p<0.05). Total sperm number and progressive motility showed significant improvements (p<0.05 for both) after 6 months of rec-FSH treatment in the group of patients with a satisfactory response to hp-FSH stimulation. In conclusion, the basal and reserve activity of Sertoli cells, as judged by inh-B secretion, was higher in normozoospermic than in dyspermic men, with a better therapeutic outcome noted in those patients with an adequate response to hp-FSH stimulation.