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B C Fauser

Publications and source records attributed to B C Fauser.

116 records · Page 7Linked to original sources

Follicle-stimulating hormone and advanced follicle development in the human.

The great majority of human oocytes is destined to undergo atresia. Only follicles able to respond to stimulation by follicle-stimulating hormone (FSH) will enter the final stage of development and ovulate. While the role of FSH in early follicle development is unclear, late follicular development is FSH-dependent. FSH levels increase during the luteo-follicular transition and give rise to continued growth of a cohort of follicles. In the normo-ovulatory cycle, one follicle achieves a diameter of >8 mm and produces high concentrations of estradiol. In response to negative feedback from rising estradiol and inhibin levels, FSH levels fall in the late follicle phase. The dominant follicle has increased sensitivity to the falling FSH levels and continues growing. Follicles that initiate the latter stages of development after FSH levels begin to fall undergo atresia. The duration of this FSH window during which FSH levels are above the threshold required to stimulate ongoing development determines the number of follicles that can develop to the pre-ovulatory stage. Recognition of this concept has resulted in new approaches in ovulation induction treatment and ovarian hyperstimulation therapy for in vitro fertilization (IVF).

Adolescent↗

Follicular development and oocyte maturation in hypogonadotrophic women employing recombinant follicle-stimulating hormone: the role of oestradiol.

Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are required for follicle development and oestrogen production. Moreover, under normal conditions a close association between dominant follicle size and serum and intrafollicular oestradiol levels is observed. With the recent availability of human recombinant FSH (recFSH), it was possible for the first time to study effects of FSH alone, in the complete absence of endogenous or exogenous LH, on ovarian function. Recent studies applying recFSH in hypogonadotrophic women have shown convincingly that normal growth of follicles up to the preovulatory stage occurs despite extremely low oestradiol levels, in keeping with previous observations using exogenous gonadotrophins in women incapable of synthesizing oestradiol due to steroid enzyme abnormalities. Insufficient data are presently available in humans to conclude whether or not oocyte quality is compromised under these circumstances. It should, however, be realized that sufficient oestradiol levels are required for fertilization in vivo. Therefore LH, or human chorionic gonadotrophin (HCG), should be added to stimulation protocols in hypogonadotrophic individuals. These observations may also be relevant for monitoring of ovarian response during recFSH therapy, especially when combined with gonadotrophin-releasing hormone agonists for ovarian hyperstimulation for in-vitro fertilization.

Estradiol↗

Regulation of follicle development and novel approaches to ovarian stimulation for IVF.

Current ovarian stimulation regimens for IVF are complex and not without risk. Increasing our knowledge of the physiology of follicle development and dominant follicle selection may enable the design of less complex, safer and cheaper ovarian stimulation regimens for IVF. Decremental serum FSH concentrations during the follicular phase of the menstrual cycle are required for single dominant follicle selection. Only the most mature follicle will continue its development due to increased sensitivity for stimulation by FSH. FSH stimulation becomes insufficient for less mature follicles and remaining cohort follicles will therefore go into atresia. The number of days during which FSH is above the threshold for stimulation of follicle development is limited, resulting in a narrow FSH window. More medium sized and large pre-ovulatory follicles and increased oestradiol output can be induced by the administration of small doses of exogenous FSH during the mid- to late follicular phase, preventing the physiological decrease in FSH stimulation. Intervention with decremental serum FSH concentrations in combination with gonadotrophin-releasing hormone (GnRH) antagonists to prevent a premature rise in serum LH may induce ongoing growth of multiple follicles sufficient for IVF. The benefits and risks of these minimal hyperstimulation protocols require further evaluation.

Female↗

Short- and long-term hormonal effects of a single dose of 50 mg tamoxifen administered to normal males.

To five potentially fertile males, a single dose of 50 mg tamoxifen was administered orally to explore the short- and long-term hormonal effects on the hypothalamic-pituitary-gonadal axis. Blood specimens were obtained through an integrated sampling technique for the first two hours after the intake of the drug. Then, samples were taken daily throughout one week, and twice weekly for the next two weeks. Hormone measurements of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and oestradiol were obtained by specific RIA. All the subjects showed different response patterns. No general characteristic of the hormonal changes in the investigated group could be given. A consistent correlation between the within-individual levels of gonadotrophin and sex steroid changes could not be observed. It is concluded, within the limits of the used experimental design, that in healthy males a single administration of tamoxifen does not result in consistent changes in serum levels of either gonadotrophins or sex steroid hormones.

Adult↗

Long-term, pulsatile, low dose, subcutaneous luteinizing hormone-releasing hormone administration in men with idiopathic oligozoospermia. Failure of therapeutic and hormonal response.

In four normal men with a history of long standing infertility, severely disturbed sperm qualities (determined in at least three spermiograms), normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (measured over a time period of 90 minutes), and lack of evidence of further andrological or other obvious endocrine disorders the effectiveness of luteinizing hormone-releasing hormone (LH-RH) treatment was investigated. LH-RH was administered subcutaneously with a portable, comterized infusion pump (Zyclomat) for 3 months, with administration intervals of 90 minutes and bolus dosages of 5 micrograms (three patients) and 20 micrograms (one patient). Semen qualities during and after LH-RH treatment, as compared to pretreatment values, showed no improvement in volume of ejaculate, number of sperms per milliliter and motility. During or at the end of the treatment period no evident differences were observed in serum LH, FSH and testosterone levels (measured over a 90 minutes period) compared with hormonal values before LH-RH therapy, nor at the low-dose (5 micrograms) neither at the high-dose (20 micrograms) administration schedule. It is concluded that pulsatile subcutaneous LH-RH treatment in normogonadotropic, oligozoospermic men does not seem to improve the therapeutical arsenal.

Adult↗

Effect of lower versus higher doses of tamoxifen on pituitary-gonadal function and sperm indices in oligozoospermic men.

Administration of the antiestrogen tamoxifen for one month to 12 patients with idiopathic oligozoospermia significantly increased the mean basal testosterone (T) level and the responses of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to constant luteinizing hormone releasing hormone (LHRH) infusion but did not significantly influence the mean oestradiol (E2) levels or the E2 over testosterone ratio. Mean sperm concentration and total sperm output increased by about 70% after a mean treatment period of 5.5 +/- 0.4 months. No statistically significant difference was found between the two subgroups of patients treated with either the lower (5 or 10 mg once daily) or higher dose of tamoxifen (10 mg twice daily) with respect to basal or LHRH stimulated gonadotropin and testosterone response or the E2/T ratio and the effect on sperm density and total sperm output. In both subgroups the sperm motility and morphology remained unchanged. In conclusion higher doses of tamoxifen in this study prove not to be superior to lower doses in improving mean sperm density and total sperm output. The relative small percentage of patients achieving normalisation of only these sperm parameters pleads for further search for more effective selection of patients and other more effective treatment modalities in patients with idiopathic oligozoospermia.

Dose-Response Relationship, Drug↗

Effect of chronic aromatase inhibition by delta 1-testolactone on pituitary-gonadal function in oligozoospermic men.

Aromatase inhibition by delta 1-testolactone (Teslac, 500 mg twice daily) for 6 months in 9 patients with idiopathic oligozoospermia lowered the levels of serum estradiol (E2) and thereby sex hormone binding globulin (SHBG) (rS = +0.40, p less than 0.025) to values -35 and -25%, respectively, below the pretreatment values (P less than 0.001 and less than 0.005). The E2 decrease was accompanied by a temporary increase (+50%) in the levels of follicle stimulating hormone (FSH), not of luteinizing hormone (LH), and of 17 alpha-hydroxyprogesterone (17 alpha-OHP), but less of testosterone (T) (+30%), which led to a transient rise in the 17 alpha-OHP/T ratio. The T/E2 ratio and "free T" index (T/SHBG) almost doubled until the end of the treatment period. During delta 1-testolactone treatment the mean sperm density gradually rose from 8.1 +/- 1.3 (SEM) before to 21.3 +/- 6.7 X 10(6)/ml after 6 months (P less than 0.01), whereas the total sperm count almost threefold increased (P less than 0.05). Sperm concentrations exceeding 20 X 10(6)/ml were achieved in 4 of the 9 patients. Two of these patients' wives became pregnant. Although the data point to a pivotal role of estrogens in the pathogenesis of the spermatogenic lesion in some patients with idiopathic oligozoospermia, the lack of a beneficial effect of estrogen lowering in others points to a multicausal nature of the disease entity.

Adult↗

Testicular steroid response to continuous and pulsatile intravenous luteinizing hormone-releasing hormone administration in normal men.

In 18 healthy normal men Leydig cell response was examined following intravenous luteinizing hormone-releasing hormone (LH-RH) administration under standardized conditions. The same total amount of LH-RH was administered for 3 hours both in a continuous (1 microgram/min; C (1,1)) and in a pulsatile fashion, by giving a 20 micrograms dose at 20 minutes intervals, P (20, 20), and a 60 micrograms dose at 60 minutes intervals, P (60, 60). Following the different modes of LH-RH administration which all caused 3-4 fold elevations of the mean endogenous luteinizing hormone (LH) concentrations and 1.7-2 fold elevations of the mean follicle-stimulating hormone (FSH) serum levels, an overt increase of the mean testosterone (T) levels was noticed up to 1.5 X the baseline value. No difference was observed in the total amount of T release among the investigated groups. The patterns of the T response, however, clearly differed from one another with a rapid increase, during the C (1, 1) and the P (20, 20) LH-RH administration, and a delayed but persistent T increase in the P (60, 60) experiment. The mean 17-hydroxyprogesterone (17-OHP) concentrations demonstrated a similar course to T in the P (60,60) experiment, while significant increases of the oestradiol (E 2) levels were never observed in all three experiments. In view of the comparable LH and FSH increments in response to LH-RH administration in either experiment the differences in T responses may be explained by assuming a direct effect of LH-RH on Leydig cell steroidogenesis in the men.

17-alpha-Hydroxyprogesterone↗