Urine selenium changes during pregnancy do not correlate with thyroid autoantibodies in a mildly iodine deficient population.

Selenium (Se) is a key component of iodinases; higher Se levels are associated with lower titers of antithyroid peroxidase antibodies (anti-TPO). Pregnancy exerts profound effects on thyroid function and autoimmunity. To assess the relationship of urine Se levels with thyroid function and autoimmunity in pregnant women residing in Athens, Greece, we studied prospectively 47 euthyroid women in uncomplicated singleton pregnancies (mean age + SD: 30 + 5 years) in each trimester, measuring urine Se levels, urine iodine, plasma thyrotropin (TSH), free thyroxine and triiodothyronine (FT4 and FT3), as well as levels of anti-TPO antibodies. Changes of the measured parameters were assessed over each trimester; thyroid parameters were assessed with relation to Se levels. Urine Se dropped by the third trimester, whereas urine iodine did not change appreciably during pregnancy. TSH and anti-TPO did not show appreciable changes; FT4 and FT3 gradually decreased as the pregnancy advanced. No relationship between urine Se levels and anti-TPO was found. During pregnancy, changes in urine Se levels accompany mild changes in thyroid function. However, we did not find some association between these changes and thyroid autoimmune activity over this period, probably because the effect of Se on thyroid autoimmunity may only become apparent in case of excess Se fortification.

An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga.

A series of studies aiming at introducing an effective treatment for idiopathic oligozoospermia was conducted in a step-wise fashion spanning over a 20-year period. The concept was that co-administration of an accessory gland-stimulating androgen, testosterone undecanoate (40 mg t.i.d.) and the FSH raising anti-oestrogen tamoxifen citrate (10 mg b.i.d.) may improve sperm parameters. A prerequisite for such an effect was the demonstration that testosterone undecanoate had no suppressing action on pituitary-testicular axis. In this context, initial studies demonstrated no change in basal or stimulated gonadotrophin and testosterone secretion in short- or long-term protocols. Two subsequent trials with this combination showed a marked improvement of sperm parameters and pregnancy incidence, with a seasonal variation noted in response to treatment, this being higher during the cold seasons of autumn and winter. Regarding the mechanism of testosterone undecanoate's action, a recent study from our unit showed that its administration resulted in a marked rise of serum DHT levels. Because this steroid is an epididymal function promoter, it appears that its contribution in the combination is mediated mainly through its DHT raising effect. By and large, this empiric approach for the treatment of idiopathic oligozoospermia was satisfactorily documented after a 20-year investigative saga.

Seasonality in sperm parameters in normal men and dyspermic patients on medical intervention.

This study attempted to investigate the presence of seasonal variations in sperm parameters and to evaluate the season's impact on the response to treatment in men with idiopathic oligozoospermia (IO). To this end, a retrospective analysis of the records of 294 men, who participated in a controlled study, was performed. This sample included IO men (n = 106) treated with tamoxifen citrate (10 mg b.i.d.) and testosterone undecanoate (40 mg t.i.d.) or placebo (n = 106) and normozoospermic men (n = 82) serving as controls. Outcome measures included sperm parameters, functional sperm fraction (FSF) and incidence of pregnancy. Analysis showed a raised frequency of high FSF values and increased area under the response curve (AURC) for FSF mean during autumn-winter seasons in patients on active treatment compared with those in placebo (P < 0.05-P < 0.04). Moreover, receiver operation characteristics (ROC) curves for a >100% FSF rise significantly discriminated autumn-winter from other seasons (P < 0.001, all), whereas active treatment showed higher than placebo FSF values particularly during autumn and winter (P < 0.001, all). The pregnancy incidence was higher in the autumn in all groups. It is concluded that FSF values showed a better response to active treatment during autumn and winter, indicating that commencement of empirical treatment at this time in IO men may stand a better chance to succeed.

Sex steroids in cervical mucus of spontaneous or induced ovulatory cycles.

Evaluation of sex steroids in cervical mucus was performed at different phases of spontaneous or clomiphene-citrate-induced ovulatory cycles. To this end, 11 women with normal ovulatory cycles and 9 subjects with polycystic ovary syndrome of comparable age and body mass index were investigated. Serum and cervical mucus samplings were assessed for 17beta-estradiol (E2), progesterone, testosterone, and sex hormone binding globulin levels at the pre-, peri-ovulatory, and mid-luteal phases of the cycle. The cervical mucus maturation index also was estimated in all women. Measurable amounts of E2 were found in most mucus samples with a cyclic variation in all cases. The highest E2 and mucus maturation index values coincided, but both lagged by 24 h behind the serum mid-cycle peak of this steroid. Detectable amounts of progesterone were found in the luteal phase, testosterone was present at low levels throughout the cycle, but sex hormone binding globulin was undetectable in all cervical mucus samples. Differences between spontaneous or drug-induced ovulatory cycles were not found. It is concluded that sex steroids are present in human cervical mucus, showing variations similar to those in peripheral blood. The significance of these findings is not clear at present, but it is probably related to the cyclic changes of cervical epithelium and gland secretion. An important implication of the absence of measurable sex hormone binding globulin amounts in cervical mucus is that the free fraction of sex steroids present in that fluid are presumably higher, and therefore, expected to exert greater biologic activity than in peripheral blood.

The combination of testosterone undecanoate with tamoxifen citrate enhances the effects of each agent given independently on seminal parameters in men with idiopathic oligozoospermia.

OBJECTIVE: To evaluate the effects of combined tamoxifen citrate and T undecanoate treatment on seminal parameters in men with idiopathic oligozoospermia. DESIGN: Prospective randomized clinical study. SETTING: A state hospital tertiary clinic. PATIENT(S): Eighty oligozoospermic men were included in the protocol. INTERVENTION(S): Patients were randomized to receive placebo, T undecanoate (40 mg three times per day), tamoxifen citrate (10 mg two times per day), or T undecanoate plus tamoxifen citrate. RESULT(S): Tamoxifen citrate plus T undecanoate treatment produced a satisfactory improvement of total sperm number, motility, and functional sperm fraction after 3 and 6 months. Comparisons with other active treatment groups showed significantly higher increment values for motility and functional fraction, whereas aniline, acrosine, and free L-carnitine also were markedly better in the combination treatment group. CONCLUSION(S): These results indicate that the combination of tamoxifen citrate with T undecanoate not only improves significantly important seminal parameters but also compares favorably with the single treatments used. Therefore, this combination deserves a place as a first line of treatment in idiopathic oligozoospermia.

Seminal volume and total sperm number trends in men attending subfertility clinics in the greater Athens area during the period 1977-1993.

The trends for such important parameters of male fertility as seminal volume and total sperm number were assessed in men living permanently in the Greater Athens area over a prolonged period of time. To this end, the records of three andrological laboratories employing the same method for semen evaluation were analysed retrospectively. Out of 23,850 men examined from 1977 to 1993 (17 years) for couple subfertility, a total of 2385 (10%) were selected for evaluation by a randomization procedure. Analysis of the data included (i) estimation of mean seminal volume and total sperm number per year, (ii) assessment of percentage frequency distribution of each seminal parameter and (iii) evaluation of seminal volume and total sperm number changes in relation to the year of observation and age of the subjects. A significant decrease (P < 0.01) of total sperm number was observed over the years with a mean (+/-SEM) of 154.3 +/- 19.2 x 10(6) at the beginning (1977), dropping to 130.1 +/- 13.3 x 10(6) in the final year (1993). Mean seminal volume was lower in the final year of observation, but its difference from the initial year value was not significant. Frequency distribution analysis showed a marked decline in the 240-400 x 10(6) sub-set of the range of sperm number values from 16.9 +/- 4.5% (1977) to 10.6 +/- 1.6% in the final year (P < 0.01). Multiple regression analysis of seminal volume, total sperm number, age and year of assessment revealed a significant decline of the two seminal parameters along the years of observation (P < 0.05 and P < 0.0001 respectively). Over the same period, a marked deterioration of some air pollution indices was observed in that area. It is concluded that in this racially and ethnically homogeneous sample of men, living under the same environmental conditions, a significant decline in seminal volume and total sperm number occurred over the 17 years of observation.

Endocrine effects of testosterone undecanoate as a supplementary treatment to menopausal gonadotropins or tamoxifen citrate in idiopathic oligozoospermia.

OBJECTIVE: To evaluate the effects of T undecanoate given as a supplementary treatment with tamoxifen citrate (TAM) or hMG on pituitary and Leydig cell function in men with idiopathic oligozoospermia. DESIGN: A total of 48 normogonadotropic men with idiopathic oligozoospermia were allocated in to six groups (n = 8 per group) treated with placebo, 40 mg T undecanoate three times per day, 10 mg TAM two times per day, T undecanoate and TAM, 75 IU/d hMG, and T undecanoate and hMG. All groups were evaluated with standard GnRH, thyrotropin-releasing hormone, and hCG tests before and on the final day of 3 months on treatment with measurements of FSH, LH, thyroid-stimulating hormone (TSH), PRL, T, E2, 17-hydroxyprogesterone, sex hormone-binding globulin, and seminal analyses (at least twice each time). RESULTS: Basal and stimulated concentrations and incremental FSH and LH values showed no differences among TAM or hMG and TAM + T undecanoate or hMG + T undecanoate treated groups. Basal, stimulated, and incremental values for TSH and PRL were elevated markedly during treatment in most groups in comparison to placebo. Basal, stimulated, and incremental T and E2 values were similar in active treatment groups except that higher T concentration was found in TAM + T undecanoate as compared with T undecanoate only treated men. Finally, significant improvements were noted in important seminal parameters and particularly in the functional sperm fraction of the TAM + T undecanoate group as compared with single treatment with TAM. CONCLUSION: These results indicate that T undecanoate in combination with TAM or hMG not only had no adverse effects on pituitary and Leydig cell activity but also seemed to improve important seminal parameters and signify that androgens may be tried as a supplementary treatment to conventional regimes in idiopathic oligozoospermia.

Testicular secretion after pulsatile human menopausal gonadotropin therapy in gonadotropin-releasing hormone agonist desensitized dysspermic men.

OBJECTIVE: To evaluate Leydig and Sertoli cell response to prolonged pulsatile stimulation with hMG after pituitary desensitization with the GnRH agonist (GnRH-a) triptoreline in normogonadotropic men with abnormal semen analyses. DESIGN: A group of four oligozoospermic men were investigated in the following manner: [1] basal and GnRH-hCG stimulated activity were assessed in all volunteers; [2] a long-acting form of the GnRH-a triptoreline (3.75 mg every month for 3 months) was given, and its effectiveness was evaluated on day 20; and [3] on that day hMG pulsatile administration was introduced (150 IU per 24 hours in 90-minute pulses) with serial hourly sampling (6 to 7 hours) for measurement of FSH, LH, T, E2, and inhibin on days 20, 41, and 90 from the first GnRH-a injection. RESULTS: Initial evaluation showed normal basal, GnRH, and hCG-stimulated hormone concentrations. Pituitary and gonadal activity were effectively suppressed by GnRH-a when tested on day 20. Pulsatile hMG had no immediate stimulatory effect on gonadal activity (day 20). However, on middle and final evaluations (days 41 and 90), basal T, E2, and inhibin had risen to pre-GnRH-a levels, and, moreover, distinct secretory pulses were seen for these hormones. CONCLUSION: These findings indicate that suppression of pituitary gonadotropin activity with triptoreline combined with pulsatile hMG stimulation offers a new, useful tool for investigation of the male reproductive system in oligozoospermic men.

Effects of induced peripheral anosmia on gonadal maturation in prepubertal male rabbits.

The effect of induced peripheral anosmia on gonadal development and maturation was investigated in sexually immature male rabbits. Furthermore, the effect of agents promoting gonadal maturation (LHRH, hMG or methyl testosterone) on testicular development was examined in anosmic rabbits. Peripheral anosmia was induced by spraying the olfactory mucosa with 5% ZnSO4 solution; its effects were evaluated after a 45-day period, corresponding to the duration of spermatogenesis. Evaluation was based on measurement of body-weight, testicular size, testicular biopsy score count (TBSC) and a standard LHRH test (0 and 30 min) involving measurement of the blood levels of FSH, LH and testosterone before and at the end of the test. Markedly lower final and incremental values were noted in anosmic, compared to intact, animals for body-weight (P less than 0.001), TBSC (P less than 0.001), FSH (P less than 0.01) and LH (P less than 0.05). On the other hand, treatment of the anosmic rabbits with 0.9% saline, resulted in lower FSH, TBSC and testicular size increments than in rabbits treated with LHRH, hMG or testosterone, while testosterone levels and body-weight increments were similar in all groups. These findings indicate that induced peripheral anosmia is probably responsible for the inadequate gonadal maturation in prepubertal anosmic male rabbits. This relationship was confirmed by the observed stimulatory effect of administration of agents activating pituitary gonadotrophin secretion or gonadal function in anosmic animals.

The origin of a human chorionic gonadotropin beta-subunit-core fragment excreted in the urine of patients with cancer.

Immunoreactive human Chorionic Gonadotropin (hCG), its subunits and hCG beta-core fragment were analyzed, using Sephadex G-100 chromatography, in urine and tumour extracts from four patients with cancer. These patients were selected for investigation because they were excreting proportionally large amounts of the hCG beta-core fragment in their urine. Although 30-85% of the total immunoreactive urinary hCG was hCG beta fragment, traces of the fragment (2% of total hCG) were found in only two of the tumours and none in the other two. The predominant molecular form of hCG in the tumours was intact free beta-subunit of hCG. The conclusion is that the hCG beta-core fragment found in the urine of some patients with cancer is not a secretion product of the tumours. This fragment is very likely a peripheral degradation product of the free beta-subunit of hCG which is secreted by the tumours.