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Biomedical subjects

L J Gooren

Publications and source records attributed to L J Gooren.

At least 109 records · Page 6Linked to original sources
PubMed1988

Effects of opiate receptor blockade on gonadotrophin secretion before and after administration of the oestrogen receptor blocker tamoxifen in eugonadal men.

Both gonadal steroids and endogenous opioid peptides (EOPs) exert an inhibitory effect on gonadotrophin secretion. It is thought that the negative feedback action of the gonadal steroids, testosterone (T) and oestradiol (E2), on the gonadotrophin secretion is mediated by EOPs. To assess the effects of EOPs and oestrogen and their interrelationship on pulsatile LH secretion we studied two groups of eugonadal men. The subjects of the first group were tested on three different occasions, firstly under basal conditions, secondly during infusion of the opiate receptor blocker naloxone (NAL) (bolus 5 mg + 2.1 mg/h for 7 h), and finally during NAL infusion after 6 weeks administration of the oestrogen receptor blocker tamoxifen (10 mg twice daily). The subjects of the second group were studied before and after 6 weeks administration of tamoxifen. NAL infusion produced a significant increase in mean serum LH levels (4.8 +/- SD 1.5 to 6.2 +/- 1.8 U/l) and LH pulse frequency (3.7 +/- 1.6 to 5.3 +/- 1.2 pulses/7 h). No change was seen in mean LH pulse amplitudes (3.5 +/- 1.5 vs 3.4 +/- 1.0 U/l). After tamoxifen administration alone there was a significant increase in mean LH level (from 5.7 +/- 1.3 to 10.1 +/- 2.4 U/l), LH pulse amplitude (from 3.8 +/- 0.9 to 4.6 +/- 0.9 U/l) and LH pulse frequency (from 4.2 +/- 1.5 to 5.8 +/- 1.7 pulses/7 h). A significant rise in mean serum LH levels was observed during NAL infusion after previous tamoxifen administration in comparison to the infusion of NAL alone (from 6.2 +/- 1.8 to 10.5 +/- 6.2 U/l). LH pulse frequency (5.3 +/- 1.2 vs 6.3 +/- 1.3 pulses/7h) and amplitude (3.4 +/- 1.0 vs 3.6 +/- 1.5 U/l) however, did not change. Mean serum LH level and LH pulse frequency after opiate receptor and oestrogen receptor blockade together did not differ from the results obtained after oestrogen receptor blockade alone. NAL however was expected not only to block opioid-mediated oestrogen action but also androgen action and therefore to have additional effect on LH secretion, whereas tamoxifen was supposed to block only oestrogen action. From these data we conclude that EOPs exert a negative feedback effect on LH secretion by slowing the GnRH pulse generator. Because there was no additional effect of opiate receptor blockade after oestrogen receptor blockade on pulsatile LH secretion we infer that androgens may be impeded in their negative feedback action in the presence of the antioestrogen tamoxifen.

Adult↗
PubMed1988

Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals.

PRL levels were evaluated during long-term treatment with cyproterone acetate 100 mg and ethinyloestradiol 100 micrograms/day orally or depot-oestrogens in 214 male-to-female transsexuals. PRL levels increased above normal in all subjects (normal less than 300 mU/l). In 46 (21.4%) subjects PRL levels rose to greater than 1000 mU/l. The incidence of PRL levels greater than 1000 mU/l was 3.7-7.2% per treatment year. Grossly elevated PRL levels were associated with high doses of oestrogens (P less than 0.05) and advanced age at the start of treatment (P less than 0.05). In 23 subjects PRL levels greater than 1000 mU/l decreased by more than 50% spontaneously (n = 5) or after dose reduction (n = 18). In five of the subgroup of 15 subjects with persistent PRL levels greater than 1000 mU/l enlargement of the pituitary gland was shown by CT-scanning. These data suggest that the lowest possible oestrogen dose and lifelong follow-up of hormone-treated male-to-female transsexuals is essential.

Adolescent↗
PubMed1988

Prevalence of transsexualism in The Netherlands.

On the basis of the records of subjects undergoing cross-gender hormonal treatment at the only gender treatment centre in the Netherlands, the prevalence of transsexualism was assessed over the years 1976-1986. In 1980, the prevalence was 1:45,000 for male-to-female and 1:200,000 for female-to-male transsexuals. In 1986 the prevalence for male-to-female transsexuals was 1:18,000, and for female-to-male transsexuals, 1:54,000. The increased prevalence is apparently due to a lower threshold for applying for medical treatment rather than to a true increase in the prevalence. Nevertheless, the calculated prevalence is higher than hitherto recorded. The ratio of male-to-female compared with female-to-male transsexuals was found to remain constant at 3:1.

Adolescent↗
PubMed1988

Estrogen-induced prolactinoma in a man.

Prolactinomas can be induced in rats by large doses of estrogens. Whether prolactinomas can be induced in humans by estrogens, however, is not known. This report describes the development of a prolactinoma in a man with previously normal plasma PRL levels after the administration of pharmacological doses of estrogen. The patient, a 26-yr-old male to female transsexual, took cyproterone acetate (100 mg/day, orally) and ethinyl estradiol (100 micrograms/day, orally) for 10 months and (surrepititiously) estradiol-17-undecanoate (100 mg, twice weekly, im) for about 6 of the 10 months. Plasma PRL levels rose from 0.05 to 5.20 U/L within 10 months (normal, 0.05-0.30 U/L). A computed tomographic scan showed a pituitary mass with suprasellar extension. After all estrogen therapy was discontinued, his plasma estradiol levels gradually declined from 2.8 to 0.77 nmol/L (normal, 0.04-0.12 nmol/L), but PRL levels rose further to 6.2 U/L. Bromocriptine treatment (2.5 mg twice daily) then was given. Plasma PRL fell gradually to 0.43 U/L and a computed tomographic scan after 5 months showed reduction in tumor size. The patient then discontinued bromocriptine treatment. Four months later his plasma estradiol level was normal, while plasma PRL had risen to 4.6 U/L, indicating autonomous PRL secretion. We conclude that 1) estrogen in pharmacological doses can induce prolactinomas in man; and 2) subjects treated with high doses of estrogen must, therefore, be surveyed for the development of such tumors.

Adult↗
PubMed1987

Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate.

The effect of androgen blockade on the normal human prostate was studied in 16 healthy volunteers opting for male-to-female gender reassignment. Their ages ranged from 19 to 27 years. After 8 weeks of treatment with Anandron, serum hormone levels indicated anti-androgenic action and physical signs of feminization appeared. Prostate volumes (measured by ultrasound) before and following Anandron treatment remained the same. After 18 months of treatment with cyproterone-acetate and ethinyl estradiol, prostate volumes again were not changed. However, histology revealed glandular atrophy and an increase in stromal tissue. The significance of these findings is discussed.

Adult↗
PubMed1987

Androgen levels and sex functions in testosterone-treated hypogonadal men.

This study investigated the correlation of sex functions in testosterone-treated hypogonadal men and in tamoxifen-treated eugonadal men in relation to blood androgen levels. Self-reported sex functions in men treated with parenteral testosterone esters (levels fall very rapidly with this type of substitution therapy) declined at levels ranging between 11 and 5 nmole/L of testosterone. Although wide variations in individual responses were noted, levels of response in given individuals appeared to be reproducible. The critical level for oral testosterone undecanoate lies between 4 and 6 nmole/L testosterone, although the relatively high levels of dihydrotestosterone in testosterone undecanoate therapy probably produce an additive effect upon sex functions. Dihydrotestosterone is capable of maintaining sex functions in hypogonadal men. There is no evidence in this study design that androgen administration in excess of the individually determined critical levels further enhances sex functions. In view of the rapidly declining blood levels of androgens with the available parenteral testosterone ester preparations, the results suggest that hypogonadal patients may benefit from a more frequent administration of these preparations.

Administration, Oral↗
PubMed1986

The effect of cyproterone acetate alone and in combination with ethinylestradiol on the hypothalamic pituitary adrenal axis, prolactin and growth hormone release in male-to-female transsexuals.

This study investigated the effects of long-term cyproterone-acetate (CA) treatment on the hypothalamus-pituitary-adrenal axis and further on the release of prolactin and growth hormone. Thirty-one male-to-female transsexuals, treated at least 3 months either with 100 mg CA alone or in combination with 50 micrograms ethinyloestradiol (EO)/day, were studied. In all of them the cortisol response to 250 micrograms Synacthen administration was comparable to that measured in controls. Six subjects treated with CA alone (group I) and six subjects treated with CA + EO (group II) underwent an insulin-hypoglycemia test. Seven eugonadal men served as controls. Compared with control values: in two subjects of group I and one subject of group II a low cortisol response was found. The mean growth hormone response was found to be lower in both groups, whereas the mean prolactin response was lower in group I.

Adult↗
PubMed1986

The anti-oestrogen tamoxifen does not interfere with the dopaminergic control of prolactin and TSH release in normogonadotrophic oligozoospermic man.

This study was designed to investigate the role of endogenous oestrogens in the dopaminergic regulation of prolactin and TSH release in 16 normogonadotrophic oligozoospermic men. Three months' administration of the oestrogen-receptor antagonist tamoxifen (10 mg twice daily), blocking oestrogen-receptors both in the CNS and peripherally, did not affect basal prolactin and TSH levels. Neither was the prolactin or TSH response to stimulation with the anti-dopaminergic agents metoclopramide (10 mg i.v.) (acting both in the CNS and peripherally) and domperidone (10 mg i.v.) (acting peripherally) affected by tamoxifen administration. The response of prolactin and TSH to metoclopramide proved to be no greater than to domperidone. It is concluded that: Endogenous oestrogens, in as far as receptor-mediated, do not affect basal or anti-dopaminergic stimulated release of both prolactin and TSH in normogonadotrophic oligozoospermic men. The anti-dopaminergic activity of metoclopramide in the release of prolactin and TSH is likely for the greater part peripheral.

Adult↗
PubMed1986

Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment.

In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men. In the latter the release of LH was greater than in eugonadal transsexual males and volunteers, which points to a different functioning of the hypothalamic-pituitary unit in normogonadotrophic oligozoospermic men. On the other hand the FSH response to LHRH stimulation was normal in these men. Three months' treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) in the normogonadotrophic oligozoospermic men stimulated basal LH, FSH and testosterone (T) levels. The fact that gonadotrophin levels rose in spite of increased T levels, suggests a role of endogenous oestrogens in the negative feedback regulation of gonadotrophin release in these men. Upon TAM treatment the first phase, the plateau and the second phase of LH release were augmented, whereas only the plateau and the second phase of FSH release were increased. Six weeks' administration of the oestrogen ethinyloestradiol (EE) (10 micrograms three times a day) in the eugonadal transsexual males suppressed basal T and oestradiol (E2) levels without affecting basal gonadotrophin levels significantly. In EE-treated males the first phase of LH release tended to be lower, whereas the plateau of LH had decreased significantly. The second phase of LH was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Effects of naloxone infusion on plasma levels of LH, FSH, and in addition TSH and prolactin in males, before and after oestrogen or anti-oestrogen treatment.

The inhibitory action of endogenous opioids on gonadotrophin release is now well documented. Since LHRH-producing neurons do not possess oestrogen-receptors, it is likely that some other compound mediates the negative feedback action of oestrogens on the gonadotrophin release in the male. To test the hypothesis that endogenous opioids are implicated in this negative feedback action in the human male, the opioid receptor antagonist naloxone (2 mg/h for 4 h) was infused into 7 normogonadotrophic oligozoospermic men before and after 6 weeks of treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) and 6 eugonadal transsexual males before and after 6 weeks of administration of ethinyloestradiol (EE) (10 micrograms three times a day). The effects of naloxone on TSH and prolactin (PRL) release were also studied. Naloxone administration resulted in a significant release of gonadotrophins, but not of TSH and PRL. Administration of oestrogen and anti-oestrogen did not significantly affect the response of gonadotrophins to naloxone infusion and no evidence of consistently antagonistic effects of oestrogen and anti-oestrogen on the naloxone-induced gonadotrophin release was obtained. This shows that endogenous opioids are probably not intermediary in the negative feedback control of oestrogens on gonadotrophin release in the human male. Surprisingly, in contrast to the eugonadal transsexual males, FSH levels in the oligozoospermic men did not respond to naloxone administration. As naloxone is thought to exert its action on gonadotrophin release via a disinhibition of endogenous LHRH release, this finding is unexpected. Exogenous LHRH administration leads to a normal response of FSH in normogonadotrophic oligozoospermic men. No plausible explanation for this finding can presently be offered.

Adult↗
PubMed1986

Long-term safety of the oral androgen testosterone undecanoate.

In 35 men treated with testosterone undecanoate (TU) at a dosage of 80-200 mg/day, liver function was measured every 6 months for a period of 72 months. None of the parameters changed. In 8 subjects of 50-62 years of age upon starting this type of treatment, urine flow was not found to decrease over the test period of 72 months. Also other signs of benign prostatic hypertrophy were not reported. In 9 subjects for whom TU was the first type of androgen treatment, no signs of gynaecomastia were found during the first 6 months of the therapy or later. These data provide evidence that TU is a reasonably safe form of oral androgen therapy.

Administration, Oral↗
PubMed1985

Human male sexual functions do not require aromatization of testosterone: a study using tamoxifen, testolactone, and dihydrotestosterone.

This study was designed to examine whether testosterone needs to be converted to estradiol in order to exert fully its effects on sexuality in the human male. Administration of the estrogen receptor antagonist tamoxifen and the aromatase inhibitor testolactone were without effect on parameters of sexual functions. Replacement of testosterone substitution therapy of agonadal men by dihydrotestosterone was likewise not associated with any change of sexual functioning. Administration of dihydrotestosterone to eugonadal men led to a transient increase of nocturnal sexual dreams and erections and irritability, waning after 3-4 weeks of dihydrotestosterone administration. It is concluded that aromatization of testosterone is not required and that dihydrotestosterone maintains sexual functions in the adult male with an established sex life.

Adult↗
PubMed1985

Studies on the prolactin-releasing capacity of luteinizing hormone releasing hormone in male subjects.

The present study examined the conditions under which LHRH is capable of releasing PRL in the human male. No such effect was found in eugonadal males. After pretreatment with 100 micrograms ethinyloestradiol/day, but not with 30 micrograms/day, the PRL-releasing action of LHRH became apparent. This indicates that high doses of oestrogens are required. This effect of LHRH on PRL release was still demonstrable two weeks after withdrawal of oestrogens. This suggests that rather than oestrogens per se, alterations in the control of PRL induced by oestrogens, render the lactotroph sensitive to LHRH. Further: No effect was observed after administration of a bolus LHRH, whereas LHRH administered as an infusion released PRL with a latency period of 20-40 minutes. The interpretation for this could be that LHRH acts indirectly via a LHRH-induced decreased dopaminergic tone, which mechanism requires a certain amount of time. It is hypothesised that a LHRH-induced decrease of dopaminergic tone together with a weakened dopaminergic control of the oestrogenised lactotroph could account for this non-specific action of LHRH on PRL release.

Adult↗
PubMed1985

Exogenous androgens decrease the length of the luteal phase and increase the length of the follicular phase.

This study investigated the effects of exogenous androgens on the menstrual cycle of eight transsexual females. It was found that the luteal phase decreased from 13.7 +/- 0.8 to 11.6 +/- 0.8 days, whereas the follicular phase increased in length from 13.5 +/- 0.6 to 15.3 +/- 0.6 days. With the testosterone levels attained in venous blood (+/- 4.5 nmol/l) ovulation continued, judged by the rise of basal body temperature and the increase of oestrogen and progesterone blood levels. These results relate hyperandrogenism to luteal insufficiency.

Adult↗
PubMed1985

Follow-up of prolactin levels in long-term oestrogen-treated male-to-female transsexuals with regard to prolactinoma induction.

As in laboratory animals, long-term oestrogen treatment in the human male might induce prolactinomas. We here report on PRL levels in 142 male-to-female transsexuals, treated with 100 mg cyproterone acetate and 100 micrograms ethinyloestradiol per day for 6-108 months (median 52). PRL levels varied markedly between individuals. No relation with age and length of treatment period was found. In 42 subjects in whom PRL levels were followed serially, a slight fall was measured after 12-15 months of treatment. Galactorrhoea, present in 10 of 142 subjects, was unrelated to PRL levels. In 34 subjects in whom PRL levels were measured during treatment and 3 weeks after withdrawal, PRL levels fell significantly. Dopamine in doses of 0.1 microgram/kg/min and 1.0 microgram/kg/min was administered to six subjects with PRL levels greater than 1000 mU/l and six subjects with PRL levels less than 500 mU/l. No difference in the percentage decrease of PRL levels was found between these two groups. However, administration of monoiodotyrosine, an inhibitor of central dopamine synthesis, to these two groups, induced a significantly smaller release of PRL (expressed as percentage change) in subjects with PRL greater than 1000 mU/l than in those with PRL less than 500 mU/1 possibly indicating a loss of control of central dopaminergic regulation. These findings suggest that the risk of inducing prolactinomas through cross-gender hormone treatment is likely to be small.

Adolescent↗