Search PubMed⌕ Search

Biomedical subjects

S J Nillius

Publications and source records attributed to S J Nillius.

At least 37 records · Page 2Linked to original sources
PubMed1984

Peptide contraception in women. Inhibition of ovulation by chronic intranasal LRH agonist therapy.

Seventy-one healthy female volunteers used the LRH superagonist D-Ser(TBU) 6-EA10-LRH (buserelin) for contraception during 3-26 months. One daily dose of 200-600 micrograms was administered by the nasal route. No pregnancy occurred during the 628 treatment months. The bleeding pattern varied from fairly regular menstrual bleedings (n = 26) to oligomenorrhoea (n = 27) and amenorrhoea (n = 18). No severe or dysfunctional bleeding disturbances were observed. No signs of hyperplastic changes of the endometrium were found in 57 endometrial biopsies. After cessation of the long-term treatment normal ovulation and menstruation returned after 41.3 days, on average. Thus, intranasal administration of an LRH agonist for inhibition of ovulation is a promising new contraceptive method for women.

Administration, Intranasal↗
PubMed1984

Luteinizing hormone releasing hormone analogues for contraception.

Peptide contraception based on LH-RH analogues is an interesting, fundamentally new lead to fertility control in women and men. A major advantage of using peptides instead of steroids for contraception is the fact that the hypothalamic peptides exert specific actions on the hypothalamic-pituitary-gonadal system and lack systemic effects. They are therefore less likely to cause metabolic derangements and other generalized adverse effects. Antagonistic analogues of LH-RH have been synthesized but until recently they have not been potent enough for clinical trials. However, chronic treatment with low doses of superactive stimulatory analogues of LH-RH paradoxically results in desensitization of the pituitary processes responsible for gonadotrophin release. This leads to a reversible inhibition of gonadal function. In women, ovulation can be inhibited by continuous intranasal LH-RH agonist treatment. In men, higher doses of LH-RH agonists have to be administered to suppress the gonadotrophin secretion enough to affect spermatogenesis. Optimal gonadotrophin suppression is, however, accompanied by a depression of the serum concentration of testosterone with loss of libido and impotence. The superagonists of LH-RH therefore have to be administered in combination with testosterone to induce oligo- or azoospermia without impotence. The overall results of clinical trials with superagonists of LH-RH for induction of inadequate corpus luteum function, luteolysis or early abortion in women are not impressive. The contraceptive effectiveness of these approaches to peptide contraception remains to be demonstrated in the human female. Inhibition of normal ovulation can, however, be consistently achieved by daily intranasal superagonist administration in women. This approach to fertility control has already been shown to provide safe and effective contraception in women.

Abortifacient Agents↗
PubMed1984

Pulsatile gonadotropin-releasing hormone therapy of anovulatory infertility.

A new treatment of anovulatory infertility has been introduced during the last few years. Pulsatile long-term administration of the hypothalamic gonadotropin-releasing hormone by means of small portable computerized infusion pumps has proved to be a safe, effective and acceptable out-patient treatment of infertility due to inadequate gonadotropin secretion. In the future, the practical pulsatile LRH treatment will in all probability to a great extent replace the present more laborious human gonadotropin therapy of anovulatory infertility.

Anovulation↗
PubMed1983

Human gonadotropin therapy. I. Serum estradiol and progesterone patterns during conceptual cycles.

Hormone patterns during 43 conceptual cycles induced by human gonadotropins in 37 women with anovulatory infertility were analyzed. The treatment was monitored by daily determinations of estradiol (E2) in serum. The incidence of both multiple pregnancies and abortions during the gonadotropin therapy was high (30%). When the hormone patterns during the human menopausal gonadotropin-induced conceptual cycles were compared with spontaneous conceptual cycles, it became evident that the ovaries were hyperstimulated during the follicular and luteal phases of the induced cycle. The mean serum E2 level at induction of ovulation did not differ between treatment courses resulting in single or multiple pregnancies. The endogenous estrogen secretion at the initiation of treatment was lower in the multiple pregnancy group than in the single pregnancy group. The active phase, i.e., when the estrogens progressively increase during the late follicular phase of the induced cycle, was found to be prolonged in the multiple pregnancy group. The prolonged follicular stimulation by human menopausal gonadotropin might explain why multiple ovulations and pregnancies occur. Thus, both the duration of the active phase of follicular stimulation and the E2 level at the day of induction of ovulation by human chorionic gonadotropin should be determined for optimal monitoring of human gonadotropin therapy.

Adult↗
PubMed1983

Human gonadotropin therapy. II. Serum estradiol and progesterone patterns during nonconceptual cycles.

Hormone patterns during 113 nonconceptual gonadotropin-induced cycles of 65 infertile anovulatory women were analyzed. All but one women ovulated, i.e., the ovulation rate was 98%. Signs of defective corpus luteum function were observed during 8 cycles, and anovulation occurred in 11 treatment cycles. The duration of the active phase of the follicular stimulation was shorter during cycles with defective luteal phases and anovulatory cycles. The mean estradiol level at induction of ovulation by human chorionic gonadotropin did not differ between the groups. Premature ovulation was observed in six treatment cycles. No case of severe hyperstimulation was encountered. The hormone pattern during gonadotropin-induced conceptual cycles did not differ in comparison with gonadotropin-induced nonconceptual ovulatory cycles.

Adult↗
PubMed1983

Pulsatile subcutaneous low-dose gonadotropin-releasing hormone treatment of anovulatory infertility.

Subcutaneous pulsatile long-term administration of low doses of gonadotropin-releasing hormone (GnRH) was given for induction of ovulation to 14 infertile amenorrheic women who did not respond to clomiphene citrate. A small peristaltic pump was used to deliver 1, 5, or 20 micrograms of GnRH every 90 minutes. Nineteen treatment courses with a duration of 26 to 187 days were given. Thirty-six ovulatory cycles were induced in 12 of the 14 women; 8 of the women conceived. Five healthy children have been born. Three early spontaneous abortions occurred. The subcutaneous GnRH therapy was given with the same pulse frequency until menstruation or pregnancy occurred. The treatment could be given without interruption to induce repeated ovulatory menstrual cycles. No serious adverse effects occurred. Subcutaneous pulsatile administration of low doses of GnRH is a promising new treatment of women with anovulatory infertility.

Adult↗
PubMed1982

Intranasal LHRH agonist treatment for inhibition of ovulation in women: clinical aspects.

Daily intranasal administration of the potent stimulatory LHRH analogue D-Ser(TBU)6-EA10-LHRH was given to fifty healthy women for 3 months. Twenty-six women received 400 micrograms LHRH agonist/day and twenty-four women received 600 microgram/day. Inhibition of ovulation occurred during 147 of the 150 treatment months. The three presumptively ovulatory cycles were probably the result of initial technical problems with the nasal spray. No pregnancies occurred. Reactivation of corpus luteum with slightly raised progesterone levels in serum at initiation of treatment was observed in six women. During 20 month treatment the serum progesterone levels were slightly raised, indicating luteinization of follicles or defect luteal phases. Most of the women had menstrual-like bleeding during treatment. Seventeen volunteers had regular bleeding and twenty-three women had oligomenorrhoea. No dysfunctional uterine bleeding occurred, but three women reported spotting. The remaining ten women had amenorrhoea during treatment without any symptoms of oestrogen deficiency. After discontinuation of treatment the women regained ovulatory menstrual cycles after 31 days on average. The treatment was very well accepted by all the women.

Administration, Intranasal↗
PubMed1982

Early follicular phase luteinizing hormone-releasing hormone agonist administration - effects on follicular maturation and corpus luteum function in women.

The potent luteinizing hormone-releasing hormone (LRH) agonist D-Ser(TBU)6-EA10-LRH was administered in a daily subcutaneous dose of 5 or 25 microgram for 1, 3 or 5 consecutive days to twelve regularly menstruating women in the early follicular phase of the menstrual cycle in an attempt to disturb follicular maturation and induce luteolysis. The treatment was monitored by clinical examinations, basal body temperature recordings, bleeding patterns and frequently taken peripheral venous blood samples for analyses of gonadotropins and ovarian steroids. The luteal phase during the LRH agonist treatment cycles did not differ in length from that of the control cycles before and after the treatment (p greater than 0.05). The maximal progesterone concentration during the luteal phase exceeded 32 nmol/l in all but one of the treatment cycles. The follicular phase of the treatment cycle was prolonged in comparison with that of the control cycles (p less than 0.01). Thus, administration of high doses of a superactive LRH agonist during the early follicular phase of the menstrual cycle prolonged the follicular phase and postponed ovulation but did not interfere with corpus luteum function in normally ovulating women.

Adult↗
PubMed1982

Failure to induce early abortion by huge doses of a superactive LRH agonist in women.

The possible abortifacient effect of the potent stimulatory luteinizing hormone-releasing hormone analogue D-Ser(TBU)6-EA10-LRH was studied in five women in early pregnancy. Four of them were treated by intravenous injections of the superactive LRH agonist in a dose of 50-125 micrograms t.i.d. for four days (total dose 600-1500 micrograms). The fifth woman discontinued treatment after the first 50 micrograms dose. The treatment was instituted on gestational day 37, 38, 40, 42 and 46. Clinical examinations and frequently taken peripheral venous blood samples for analyses of human chorionic gonadotropin and ovarian steroids were used for monitoring the treatment. No abortifacient effects of these large doses of the superactive LRH agonist were observed and the pregnancies had to be terminated by suction curettage after 10-13 days. Thus, previously described luteolytic effects by superactive LRH agonist are overcome probably by endogenous chorionic gonadotropin in early human pregnancy.

Abortion, Induced↗
PubMed1982

Bromocriptine-induced pregnancies in women with large prolactinomas.

Fourteen women with large prolactinomas experienced a total of nineteen bromocriptine-induced term pregnancies. None of the women had received prior pituitary tumour therapy. Post-partum sellar X-ray examinations showed signs of tumour enlargement in two women. Only one of them had clinical symptoms of tumour expansion with visual field defects during the pregnancy. The visual impairment improved when bromocriptine treatment was reinstituted and the pregnancy continued to term. The other twelve women had a total of seventeen uneventful pregnancies without symptoms or signs of pituitary tumour expansion. Thus, medical therapy with dopamine receptor agonists is the primary treatment for most infertile women with prolactinomas. The risk of serious pregnancy-induced tumour expansion is very small in properly investigated and carefully supervised patients with large PRL-secreting pituitary adenomas.

Adult↗
PubMed1982

Failure of positive feedback of oestradiol during chronic intranasal luteinizing hormone-releasing hormone agonist treatment.

An oestrogen provocation test was performed in five healthy women during chronic intranasal treatment with 400 or 600 micrograms of the superactive LHRH agonist D-Ser(TBU)6-EA10-LHRH daily. Oestradiol benzoate 2.5 mg was administered intramuscularly after at least 3 months of LHRH agonist treatment. The serum levels of FSH and LH were not affected by the oestrogen injection. Failure of positive feedback of oestradiol may be one explanation for the inhibition of ovulation which occurs during chronic LHRH agonist treatment.

Adult↗
PubMed1982

Menstrual function and serum prolactin levels after long-term bromocriptine treatment of hyperprolactinaemic amenorrhoea.

Long-term bromocriptine treatment was discontinued in thirty-seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty-seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but only three were normoprolactinaemic 3 months after stopping treatment. Two of the seven women had evidence of pituitary tumour regression. After the discontinuation they had nearly normal prolactin levels but during 2 years of follow up the serum prolactin levels slowly increased. In the twenty-seven women with pre treatment prolactin levels below 100 micrograms/I there was no difference between the prolactin levels before starting and 1 month after stopping treatment, while the women with pretreatment prolactin levels above 100 micrograms/l had lower levels after therapy. Bromocriptine treatment seldom results in permanent cure of hyperprolactinaemic amenorrhoea.

Adult↗
PubMed1982

Chronic pulsatile low dose GnRH therapy for induction of testosterone production and spermatogenesis in a man with secondary hypogonadotropic hypogonadism.

Prolonged intermittent treatment with low doses of GnRH was given to a 23-yr-old man with secondary hypogonadotropic hypogonadism. The patient had experienced sudden onset of diabetes insipidus followed by progressive decrease of gonadotropins and gonadal function. Modern radiological techniques did not reveal any organic genesis. A small portable computerized infusion pump connected to a sc catheter was used for the 220-day GnRH therapy. One microgram gnRH was administered every 90 min during the first 90 days and 5 micrograms GnRH every 90 min during the following 130 days. During the prolonged GnRH treatment testosterone secretion normalized, libido and potency improved, and ejaculation returned. Spermatogenesis became close to normal and the subject's wife became pregnant after 181 days of treatment. The prolonged treatment with the small infusion pump was well accepted and did not interfere with the patient's daily life activations. Thus, chronic pulsatile low dose GnRH treatment can restore normal pituitary-gonadal function in idiopathic male hypogonadotropic hypogonadism.

Adult↗
PubMed1982

Rapid regression of pituitary tumours during bromocriptine treatment of women with hyperprolactinaemia.

Four hyperprolactinaemic women with large pituitary adenomas with suprasellar extension were given primary tumour therapy with bromocriptine. The treatment resulted in rapid tumour regression in all the women, as verified by repeated computerized tomography (CT) scans. Pronounced visual field defects were present in three of the four women before treatment. All of them had marked improvement of vision within a few days after the initiation of bromocriptine therapy and they regained normal or nearly normal visual fields during the treatment. The raised serum prolactin concentrations decreased to normal levels in all the women. Thus, medical treatment with bromocriptine can induce rapid tumour regression in patients with hyperprolactinaemia and large pituitary tumours.

Adenoma↗
PubMed1982

Long-term intranasal luteinizing hormone-releasing hormone agonist treatment for contraception in women.

Fifty-one female volunteers used a superactive stimulatory luteinizing hormone-releasing hormone (LH-RH) analog for suppression of ovulation for 3 to 12 months. The potent LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was administered intranasally once daily in a dose of 400 or 600 micrograms. No pregnancies occurred during the 283 treatment months. Severe bleeding disturbances were not observed during the long-term treatment. No signs of hyperplastic changes were found in endometrial biopsies. There were no serious side effects. Ovulation promptly returned after cessation of treatment even in women with amenorrhea during treatment periods of 1 year or more. Thus, long-term LH-RH agonist treatment proved to be a safe, effective, and rapidly reversible new method for peptide contraception.

Administration, Intranasal↗
PubMed1982

Comparison between tamoxifen and clomiphene for induction of ovulation.

The effectiveness of tamoxifen and clomiphene in inducing ovulation was compared in 46 women with anovulatory infertility. All the women were given both the drugs in an alternate way. If one cycle was treated by tamoxifen the next was treated by clomiphene and vice versa. Forty-one out of the 46 women (89.1%) ovulated at least once during the study. Similar ovulation rates were achieved by tamoxifen (56.2%) and clomiphene (62.9%). The lengths of the ovulatory cycles and their luteal phases and the mid-luteal phase serum progesterone levels did not differ significantly between the two compounds. Nor did the occurrence of luteal phase defects during the tamoxifen and clomiphene treatment cycles differ. Thirty-seven of the 46 women (80.4%) responded similarly to both drugs. Thus, tamoxifen is just as effective as clomiphene in inducing ovulation in women with anovulation.

Adolescent↗