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Biomedical subjects

S J Nillius

Publications and source records attributed to S J Nillius.

At least 19 recordsLinked to original sources

Intranasal gonadotropin-releasing hormone agonist as a contraceptive agent.

The stimulatory luteinising hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered intranasally once daily to twenty-seven regularly menstruating women to determine its efficacy as a contraceptive agent. Ovulation was inhibited during all but 2 of the 89 treatment months. The failures were due to initial technical problems with the nasal spray. Twenty-one of the twenty-seven women had slight menstrual-like anovulatory bleeds during the 3--6 month trial. The remaining six women were amenorrhoeic. Ovulatory menstrual cycles rapidly returned after discontinuation of treatment. There were no serious side-effects.

Administration, Intranasal

Bromocriptine treatment of seven women with primary amenorrhoea and prolactin-secreting pituitary tumours.

Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle-stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone-releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46-2900 microgram/l) in all but one woman, in whom the prolactin level decreased from 160 to 38 microgram/l. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.

Adenoma, Chromophobe

Reduced gonadotropin secretion in postmenopausal women during treatment with a stimulatory LRH analogue.

The potent and long-acting LRH agonist D-Ser(TBU)6-EA10-LRH was administered in a daily subcutaneous dose of 5 microgram to 5 postmenopausal women for a period of 10 days. The LRH analogue produced a significant decrease in both the basal FSH and LH levels and the gonadotropin responses to the agonist. The estrogen levels in serum remained unchanged during the study period. The results suggest that D-Ser(TBU)6-EA10-LRH has a direct inhibitory effect at the pituitary level.

Aged

Inhibitory effects on gonadotrophin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue.

Long-term treatment with the potent and long-acting stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was given to 4 healthy men to study its effects on pituitary gonadotropin secretion and gonadal function. Five micrograms of the LRH agonist was self-administered sc once daily over 17 weeks. Weekly basal blood samples were obtained for determination of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolacting (PRL) and testosterone. The gonadotrophin responses to the LRH analogue were also determined during the treatment period. LRH tests were performed after treatment. Seminal fluid specimens were collected during and after treatment. A reduction of the basal serum gonadotrophin and testosterone levels were observed during the treatment period. The FSH and LH responses to the analogue were also diminished. After discontinuation of treatment the gonadotrophin and testosterone concentrations returned to pre-treatment levels within a week. The PRL levels and the seminal fluid specimens did not show any significant changes during the study period. The results suggest that chronic treatment with D-Ser(TBU)6-EA10-LRH has an inhibitory effect on the pituitary gonadotrophin secretion in healthy men. It seems likely that the reduced testosterone level is secondary to the diminished gonadotrophin secretion.

Adult

Pituitary responsiveness to luteinizing hormone-releasing hormone during treatment with subdermal D-norgestrel implants in women.

It has previously been reported that subdermal implants containing d-norgestrel inhibit ovulation through blockage of the positive feedback action of estrogen on luteinizing hormone (LH) release. In this study 100 micrograms of LH-releasing hormone (LRH) were injected intravenously to test the pituitary reserve capacity for gonadotrophin secretion in three women with three 40 mg d-norgestrel rods implanted subdermally for more than one year. The gonadotrophin release to LRH varied and seemed related to the ovarian steroid concentrations at the time of the LRH infusion in a manner similar to that seen during the normal menstrual cycle. It is concluded that low plasma levels of d-norgestreol do not inhibit the pituitary responsiveness to LRH. The results indicate that the blocking action of the gestagen on the positive feedback of estradiol on LH release occurs at the hypothalamus or higher CNS centers.

Adult

Effects of prolonged luteinizing hormone-releasing hormone therapy on follicular maturation, ovulation and corpus luteum function in amenorrhoeic women with anorexia nervosa.

Nine amenorrhoeic women with anorexia nervosa (AN) were given long-term treatment with 500 microgram of synthetic luteinizing hormone-releasing hormone (LRH) every 8 h. All the women had impaired luteinizing hormone (LH) secretion and no evidence of endogenous oestrogen production. Three of them also had deficient follicle-stimulating hormone (FSH) secretion. The pituitary reserve capacity for gonadotrophin secretion was normal but the response pattern to LRH was similar to that described in prepubertal girls. The constant administration of LRH normalized basal LH and FSH secretion and induced a cyclical gonadotrophin secretory pattern with differential changes of the LH and FSH responses to LRH during the treatment. LRH-induced gonadotrophin secretion produced follicular growth and maturation in all the women. Presumptive ovulation also occurred during the 8 treatment courses in which only LRH was administered. However, inadequate luteal phases were observed during 6 of these 8 cycles. Combined therapy with LRH and human chorionic gonadotrophin (HCG) during 5 treatment courses resulted in normal ovulatory cycles with adequate corpus luteum function.

Adult

Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumors.

Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy.Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective.

Abortion, Spontaneous

Regression of a prolactin-secreting pituitary tumor during long-term treatment with bromocriptine.

A nulliparous woman with 12 years of amenorrhea, galactorrhea, and hyperprolactinemia and radiologic evidence of a pituitary macroadenoma was treated with large doses of bromocriptine. During treatment the greatly increased prolactin levels normalized and ovulatory menstrual cycles were regained after 48 weeks of treatment. A transsphenoidal surgical exploration of the pituitary fossa was performed after 27 months of treatment. The findings at surgery suggested that regression of the pituitary adenoma had occurred during the prolonged treatment with bromocriptine. After discontinuation of the therapy, the patient continued to ovulate and subsequently conceived.

Adenoma

Serum prolactin and gonadotrophin levels before and after luteinizing hormone-releasing hormone in the investigation of amenorrhoea.

An intravenous luteinizing hormone-releasing hormone (LRH) test was performed in 287 women with amenorrhoea. Prolactin, progesterone and oestrogens in serum were also measured. Twenty-four women with premature ovarian failure and 9 with gonadal dysgenesis had raised basal follicle-stimulating hormone (FSH) levels. Neither the basal luteinizing hormone (LH) level nor the gonadotrophin responses after LRH gave a better separation of this group of women with irreversible ovarian failure. Measurement of prolactin levels were valuable in that 15 of 42 patients with hyperprolactinaemia had a radiologically abnormal pituitary fossa, whereas pituitary fossa abnormalities were found in only 11 of 245 normoprolactinaemic women. It was thought that 181 women had functional amenorrhoea; 54 per cent of these women had developed amenorrhoea in relation to weight loss and 32 per cent in relation to discontinuation of oral contraceptives. A strong correlation was found between the body weight and the basal gonadotrophin levels. The basal LH levels were correlated with serum oestrogen levels, the basal FSH level and the LH response to LRH. Most of the patients with low basal LH values had developed amenorrhoea in relation to self-imposed weight-loss. The responses to LRH were often impaired in the underweight patients but became normal after weight gain. The polycystic ovary syndrome (PCO) could not be diagnosed by measuring either basal or LRH-stimulated gonatrophin levels. Single FSH and prolactin determinations in serum seemed to be the only indispensible hormone assays in the routine clinical evaluation of amenorrhoea.

Adolescent

Prolactin.

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Amino Acid Sequence

Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue--a new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5 microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular menuration and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.

Adult

Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue - a new approach to birth control?

A stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser (TBU)6-EA10-LRH was administered subcutaneously once daily in a dose of 5/microgram to four regularly menstruating women. Treatment was instituted within the first three days of the menstrual bleeding and continued for 22--30 days. Ovulation was inhibited in all the women during the treatment cycle. The treatment resulted in disturbances in the pituitary gonadotropin secretion which presumably led to disordered follicular maturation and anovulation. The maximum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to the LRH analogue were obtained during the first few days of treatment. The gonadotropin responses then rapidly decreased during the prolonged treatment. This change in the pituitary responsiveness probably prevented the release of a normal preovulatory LH surge. After the treatment, all the women resumed normal ovulatory menstrual cycles. The results suggest that it might be possible to use stimulatory LRH analogues for birth control.

Adult

Hyperprolactinaemia in amenorrhoea - incidence and clinical significance.

Prolactin concentrations in serum were determined in 287 women with amenorrhoea. The incidence of hyperprolactinaemia was 14.6 per cent. All but 4 of the 31 women with persistent hyperprolactinaemia had galactorrhoea. Radiological signs suggestive of a pituitary tumour were seen in 48 per cent of the hyperprolactinaemic women, while only 4.5 per cent of the 245 normoprolactinaemic women had abnormal sellar X-rays. All the patients with prolactin concentrations above 100 microgram/1 had radiologically abnormal sellae, but lower prolactin levels did not rule out the existence of even large pituitary tumours. The hyperprolactinaemic women with normal and abnormal sellae and a control group of healthy women in the early follicular phase all had similar mean basal FSH and LH levels with one exception, the group with abnormal sellae had lower basal LH levels than the control group. There was no difference in the mean FSH and LH responses to LH-RH between the hyperprolactinaemic women with pathological sellae and the control group while the hyperprolactinaemic women with normal sellae had higher responses than the other two groups. Prolactin determinations were found to be superior to other pituitary hormone estimations for identifying patients who are at risk of having pituitary tumours.

Adolescent