Buserelin Treatment Research Articles

Wirkung des GnRH-Analogons Buserelin auf die Serum- Spiegel von Sexualhormonen in Abhängigkeit von Behandlungsbeginn und Behandlungsdauer

Changes of serum estradiol, progesterone, LH, FSH, prolactin, testosterone, androstendione, DHEA and DHEAS levels during a GnRH-analogue (buserelin) treatment have been analysed retrospectively taking account of effectiveness of treatment and its relation to the beginning and duration of treatment. 1200 micrograms/day buserelin were administered intranasally from the first day of the menstrual cycle (n = 30) or the 7th hyperthermic day of the cycle (n = 22). The results proved, that the administration of buserelin to sterile women inhibits the ovarian (estradiol, progesterone) and pituitary (LH, FSH) hormone secretion during the first 10-14 days of treatment. The adrenal hormone secretion (DHEA, DHEAS) remained unaffected, whereas the androgens of ovarian origin (testosterone, androstendione) were suppressed during the GnRH analogue treatment. The serum prolactin level increased during the first two weeks of treatment and returned to pretreatment values within the following two weeks. On the basis of the faster suppression of estradiol secretion with buserelin treatment, beginning in the middle of the luteal phase, this therapy is recommended for ovarian suppression.

Changes in thromboxane A 2 generation and plasma lipid pattern in pseudomenopause induced by gonadotropin releasing hormone (GnRH) analogue buserelin

An increased risk of cardiovascular disease has been found in postmenopausal women in comparison to premenopausal women. The aim of this study was to investigate platelet function, blood clotting and plasma lipid levels in 12 women with a condition of hypoestrogenism, similar to the postmenopausal status induced by treatment with the GnRH analogue buserelin for uterine leiomyoma. Platelet aggregation in whole blood and platelet-rich plasma (PRP), serum thromboxane (TX) B 2 production, fibrinopeptide A (FPA) plasma levels and plasma lipid pattern were measured before and after 13 weeks of buserelin treatment. No changes of platelet aggregability were found either in whole blood or PRP. Serum TXB 2 generation increased significantly after 13 weeks of therapy (p < 0.001). No signs of increased thrombin generation were found, as indicated by unchanged FPA plasma levels. Total cholesterol plasma levels were found increased after 13 weeks, LDL cholesterol levels showed a tendency to increase although not significantly. HDL cholesterol and triglyceride concentrations were unaffected. The changes of arachidonic acid metabolism and lipid pattern suggest that buserelin treatment may induce a condition of increased thrombotic risk even if the lack of enhanced thrombin generation and increased platelet aggregability indicates that no blood clotting activation occurs.

Management of submucous uterine fibroid with buserelin, gemeprost and hysteroscopic resection

A 19-year-old virgin presented with severe menorrhagia and a haemoglobin level of 76 g/L as a problem of management. A 5 cm diameter submucous fibroid was identified at hysteroscopy and biopsied but was unable to be removed. The luteinising hormone releasing hormone agonist, buserelin, was used in an attempt to produce symptomatic relief. One week after commencing buserelin therapy, severe menorrhagia occurred and the patient was admitted to hospital with a haemoglobin concentration of 24 g/L. Buserelin treatment was continued and no further menstruation occurred over the following year. As the patient was now well, hysteroscopic submucous fibroid resection was contemplated. Due to cervical rigidity in this teenager, a 1 mg gemeprost pessary was inserted into the posterior vaginal fornix three hours before surgery. This allowed an operative hysteroscope to be inserted into the uterus and a fibroid resection to be performed. Menstrual blood loss has been normal for six months after hysteroscopy. A combined medical and surgical approach may avoid hysterectomy in such problem patients.

Response of circulating gonadotropin levels to GnRH agonist treatment in prostatic cancer.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) responses to 6-month treatments with a gonadotropin-releasing hormone (GnRH) agonist (buserelin) and subsequent orchiectomy were studied in patients with advanced prostate cancer. For treatments, either an intranasal (600 micrograms, 3/day, n = 8) or subcutaneous depot preparation (6.6 mg every other month, n = 5) were used. A third group of patients received intranasal buserelin (400 micrograms, 3/day, n = 12) for 35 months. LH and FSH were measured using radioimmunoassay (RIA) and a sensitive (0.04 IU/L) immunofluorometric assay (IFMA). In addition, selected samples were analyzed for bioactive (bio) LH. The RIA-LH levels decreased 70% with intranasal treatment. In contrast, when monitored by IFMA, the reduction was greater than 90%: 0.2 to 0.3 IU/L with intranasal and 0.044 to 0.052 IU/L with depot treatment (P less than 0.01). Gonadotropin suppression was stable up to 35 months. Bio-LH and IFMA-LH levels decreased in parallel during treatment, with no apparent changes in the bio/immuno ratio. FSH levels were suppressed temporarily during the treatments. After castration and cessation of buserelin treatment, serum LH and FSH increased rapidly in the intranasal treatment group but only marginally during 3 months in the depot group. Serum T reached the castrate range when IFMA-LH decreased below 0.5 IU/L. A further decrease in LH (less than 0.1 IU/L) still suppressed the intratesticular T concentration measured after orchiectomy. In conclusion, IFMA offers an improved method to monitor the antigonadotropic effect of GnRH agonist treatment. The results emphasize the necessity of profound LH suppression to achieve maximal inhibition of testicular androgen production.

Intranasal buserelin versus surgery in the treatment of uterine leiomyomata: long-term follow-up

Forty-two women with symptomatic uterine myomas, candidates for myomectomy or hysterectomy, were randomized to 6 months' treatment with buserelin 1200 μg/day intranasally ( n = 22) or immediate surgery ( n = 20). After buserelin treatment or operation the patients were followed for at least 12 months. Busereliin was well tolerated, the uterine volume fell from 465 ± 168 to 273 ± 88 cm 3, and hemoglobin values normalized in all anemic patients. Rapid myoma regrowth was observed in all patients in the buserelin group after treatment withdrawal. Pregnancy occurred during follow-up in one of five buserelin-treated myomectomy candidates. Menorrhagia recurred in eight of 15 buserelin-treated hysterectomy candidates, and a hysterectomy was required but no transfusion was needed. Two women entered natural menopause and were considered cured. In the surgery group all operations were uneventful: three women conceived after myomectomy, whereas four of the patients that underwent hysterectomy required transfusions. Thus buserelin treatment appears to be indicated for infertile patients when surgery is contra-indicated or could cause adhesions, and for hysterectomy candidates in perimenopausal age and/or with secondary anemia.

Effects of a GnRH agonist (Buserelin) on LH secretion in post-partum beef cows

Plasma LH concentrations were monitored in post-partum beef cows treated with the GnRH agonist Buserelin, administered via biodegradable implants. Animals were given either untreated Buserelin implants (Group 1, n = 6) or implants that had been preincubated for 7 (Group 2, n = 6) or 14 (Group 3, n = 6) days. Control cows were sham-implanted (Group 4, n = 3). The implants were inserted subcutaneously at a mean time of 25 ± 2.8 days after caiving, and LH concentrations were monitored over 8 h periods of blood sampling (samples taken at 10 min intervals) undertaken on Days — 2, 1, 2, 3, 7, 14, 21 and 28 (Day 1 was the day of implantation). In all animals treated with Buserelin, plasma LH concentrations increased within 1 h of implantation to reach a maximum concentration (mean 35.4 ± 2.86 ng ml −1) within 4 h. In all three Buserelin-treated groups, mean LH concentrations were higher on Day 1 ( P < 0.001) and on Days 2 and 3 ( P < 0.05) than on Day — 2, before the start of treatment. On subsequent sampling days (Days 7, 14, 21 and 28), mean LH concentrations did not differ significantly from pretreatment values, but on Days 14, 21 and 28, mean LH concentrations were lower ( P < 0.05) in Buserelin-treated than in control cows. There were no significant differences in either the magnitude or the duration of the LH response between Buserelin treatment groups. Before treatment, LH episodes occurred with a mean frequency of 1.9 ± 0.4 episodes per 8 h, and in control cows occurred at a frequency of 2.3 ± 0.2 episodes per 8 h throughout the 28-day sampling period. In contrast, LH episodes were not recorded in any of the Buserelin-treated cows on the first 3 days after implantation, and were recorded in only 1 of 18, 2 of 18, 1 of 18 and 4 of 18 animals on Days 7, 14, 21 and 28, respectively. Following luteal regression, plasma progesterone concentrations remained low for the remainder of the sampling period (mean 18.2 ± 1.2 days) in 17 of 18 Buserelin treated cows. These results demonstrate that Buserelin treatment induces a short period of increased LH secretion, after which there is a prolonged period of suppression of LH release which blocks ovulation.

The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene (DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 microgram, 0.2 microgram, 1 microgram, 5 micrograms, and 20 micrograms. Buserelin was used in a 2 x 5 micrograms/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progesterone (PgR) receptor contents of the mammary tumors were not changed. In contrast, buserelin treatment caused highly significant tumor remission. The combined treatment with sandostatin and buserelin did not alter the treatment results obtained after treatment with buserelin alone. In conclusion, sandostatin treatment in this tumor model had no direct growth inhibitory effect and did not cause an endocrine inhibition of mammary tumor growth. However, these results do not exclude antitumor effects in human breast cancer in view of the presence of somatostatin receptors in approximately 20-45% of human tumors, besides possible different endocrine effects.

Cytogenetic analysis of unfertilized oocytes retrieved after treatment with the LHRH analogue, buserelin

Chromosome analysis is reported on 155 oocytes from an in-vitro fertilization (IVF) programme in which the LHRH analogue, buserelin, was used in the superovulation regime. Seventy-one oocytes had the normal number of metaphase II chromosomes. Hyperhaploidy was apparent in four cases only; doubling this figure to include the reciprocally formed hypohaploid oocytes gave an aneuploidy rate due to non-disjunction of 10%. This is close to the figure for naturally occurring aneuploidy which may be calculated from data on recognized conceptions at a comparable maternal age. Taken together with the suggestion of a maternal age effect in our series these data suggest that follicular stimulation regimes which precede IVF do not necessarily add to the naturally high aneuploidy rate of the human species. Thirteen oocytes had failed to form the first polar body and the presence of diploid mitotic or sperm chromosomes provided evidence of fertilization and arrested development in 15. These figures for chromosomal anomalies following buserelin treatment are not significantly different from those obtained from comparable surveys following clomiphene citrate stimulation, providing no evidence that the improved pregnancy rate with buserelin is due to chromosomal factors.

PROLONGED TREATMENT WITH THE GnRH ANALOGUE BUSERELIN DOES NOT AFFECT α‐SUBUNIT PRODUCTION BY THE PITUITARY GONADOTROPH

Seven patients with metastatic prostatic cancer were treated with biodegradable implants of the GnRH analogue buserelin and six were treated with buserelin intranasally. After 4-24 weeks of treatment mean serum testosterone concentrations were significantly lower in the patients treated with implants than in those treated intranasally (0.7 vs 1.7 nmol/l respectively; P less than 0.01). Also, serum LH concentrations were significantly lower in the group treated with implants. Serum alpha-subunit concentrations were significantly higher than pretreatment values during buserelin treatment. However, the sum of the concentrations of alpha-subunit present either as free alpha-subunit or as a part of LH did not differ significantly from pre-treatment values after 8 weeks or more of buserelin treatment. During buserelin treatment serum LH concentrations measured by radioimmunoassay (RIA) were higher than those measured by immunoradiometric assay (IRMA). Cross-reactivity of alpha-subunit in the LH RIA accounted for many, but not all, of the observed discrepancies. We conclude that: (1) the principal long-term effect of prolonged buserelin administration on the pituitary gonadotroph is the suppression of LH beta production, while alpha-subunit production is not affected; (2) the serum concentrations of bioactive LH are better reflected by LH concentrations measured by IRMA than by those measured by RIA. (3) Subcutaneous application of biodegradable buserelin implants is more effective in suppressing serum LH and testosterone concentrations than intranasal buserelin application.

LHRH Analogue Treatment for the Prevention of Premenstrual Attacks of Acute Porphyria

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

Use of buserelin in an FVF programme for pituitary —- ovarian suppression prior to ovarian stimulation with exogenous gonadotrophins

Daily s.c. injections of buserelin were commenced in the mid-luteal phase of the preceding cycle in 118 women undergoing in-vitro fertilization (IVF) and embryo transfer. Ovarian and pituitary suppression was said to have been adequately achieved when serum oestradiol was less than 50 pg/ml, serum LH less than 2.0 IU/l, no ovarian cysts greater than or equal to 10 mm diameter were present and menstruation had occurred. Nine groups of women were retrospectively identified after the administration of buserelin for 12 days according to whether pituitary and ovarian suppression had been achieved or not, and the reason for extended buserelin treatment prior to ovarian stimulation. Upon adequate suppression, patients were grouped in terms of the duration of exposure to buserelin, and ovarian stimulation was then started by daily injections of human menopausal gonadotrophin. There appeared to be no differences in the ovarian response for women down-regulated by day 12, 19 or greater than or equal to 26 days; those women requiring extended buserelin treatment did equally well compared to those women down-regulating quickly, in terms of number of oocytes recovered and fertilization rate. Clinical pregnancy rates per embryo transfer were 27/68(40%), 8/33(26%) and 4/17(24%) for those women down-regulated by days 12, 19 or greater than or equal to 26 respectively, and were not significantly different.

Luteinizing hormone‐releasing hormone analogue (Buserelin) treatment for central precocious puberty: A multi‐centre trial

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist

Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.

Growth Hormone and Somatomedin-C Secretion in Patients with Polycystic Ovarian Disease

Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Buserelin treatment of advanced prostatic cancer: A phase II study

From August 1986 to September 1988, 76 eligible patients with advanced prostatic carcinoma, measurable or evaluable disease, no previous hormonal treatment, were treated with Buserelin at a dosage of 500 micrograms every 8 h for 7 days, followed by 400 micrograms intranasally three times a day. No concomitant antiandrogens were administered. In the 63 evaluable patients (11 patients not yet evaluable because of short treatment time, two lost to follow-up), three complete remissions, 28 partial remissions, 30 stable disease and two progressions were obtained (National Prostatic Cancer Project criteria). Median duration of response was 55+ weeks. Side effects were modest, mostly related to the endocrinological effects of Buserelin. Transient increase in serum testosterone levels was found in 37% of the evaluable patients, but transitory 'flare-up' was present in seven patients only. With a median follow-up time of 11.5 months, median survival has not been reached. In conclusion, this study confirmed the activity of Buserelin and the feasibility of its middle-term administration.

The use of a short regimen of buserelin, a gonadotrophin-releasing hormone agonist, and human menopausal gonadotrophin in assisted conception cycles

The outcome of in-vitro fertilization treatment using buserelin, an agonist of luteinizing hormone releasing hormone, given in a short stimulation regimen with human menopausal gonadotrophin (HMG), was compared with a conventional regimen including clomiphene citrate (CC). A total of 94 infertile women underwent cycles of treatment with intranasal buserelin, 500 micrograms daily from the first day of menstruation and also HMG daily from the third day. The same patients had previously undergone unsuccessful treatment cycles with CC and HMG. Overall, addition of buserelin resulted in fewer cycles being abandoned (10 versus 34%) and none of the patients ovulated prior to collection. The mean total dose of HMG required was increased by 74% in buserelin cycles. Significantly more oocytes were collected with buserelin treatment (mean 5.9 versus 4.4, P less than 0.01) and, thus, significantly more embryos were transferred (mean 2.3 versus 1.2, P less than 0.0001) although fertilization and cleavage rates were unchanged. Fifteen pregnancies were achieved, giving a clinical pregnancy rate of 22% per embryo transfer. These pregnancies resulted in 16 live births (7 singletons, 3 twins, 1 triplets). Four pregnancies failed before 14 weeks gestation. We conclude, therefore, that the substitution of buserelin for CC for ovarian stimulation in poor responders results in an improved outcome, both in terms of the number of oocytes collected and the pregnancy rate per treatment cycle.

A new way to induce oestrogen-deficiency osteopaenia in the rat: comparison of the effects of surgical ovariectomy and administration of the LHRH agonist buserelin on bone resorption and composition

Prolonged administration of LHRH agonist suppresses pituitary gonadotrophin secretion, thereby lowering blood oestrogen. This study was undertaken to compare the osteopaenic effects of bilateral ovariectomy and chronic administration of the LHRH agonist, buserelin, in the rat. Four groups of animals which had their skeletons labelled with 45Ca were studied for 4 weeks. Group 1 underwent a sham-ovariectomy, group 2 were surgically ovariectomized, group 3 were given buserelin by daily s.c. injection and group 4 were given a continuous infusion of buserelin by osmotic minipump. Plasma concentrations of oestradiol were measured weekly. Bone resorption was assessed by measuring the urinary excretion of 45Ca and hydroxyproline and determining bone 45Ca content. Ovariectomy and buserelin treatments lowered blood oestradiol, increased biochemical indices of bone resorption and decreased femur and total body calcium and 45Ca values. The degree of oesteopaenia elicited by ovariectomy and buserelin treatment was similar. Bone responses to s.c. buserelin and to continuous buserelin infusion were alike. We attribute evidence of increases in bone resorption and induction of osteopaenia with buserelin treatment to hypo-oestrogenism. We have shown for the first time by bone analysis that buserelin induces osteopaenia as effectively as bilateral ovariectomy. This appears to be the first demonstration in the rat that long-term administration of LHRH agonist influences bone. Administration of buserelin provides a new way of inducing oestrogen-deficiency osteopaenia in the rat without removing the ovaries.

Pituitary and ovarian suppression rate after high dosage of gonadotropin-releasing hormone agonist

Ten infertile menstruating women were treated with daily injections of gonadotropin-releasing hormone agonist (GnRH-a). The GnRH-a (Buserelin; Hoe 766, Hoechst-AG, Frankfurt/Main, West Germany) was administered subcutaneously (SC) from day 9 of the cycle for 6 days, and intranasally (1.2 mg) for 15 days. Before treatment, all ten women had a normal response to Buserelin challenge test and the GnRH test, and seven of the ten responded to estradiol (E2) benzoate test (2 mg intramuscularly). The SC administration of Buserelin (1.5 mg) for 6 days resulted in suppression of pituitary activity. Continuous treatment with Buserelin (1.2 mg for 3 weeks) was effective as demonstrated by decreasing serum E2 levels to below 20 pg/ml, and in the absence of ovarian follicles in ultrasonographic scanning. Three days after cessation of Buserelin treatment, the pituitary again responded to the GnRH test. Thus, the authors concluded that the administration of Buserelin in very high doses can induce medical hypophysectomy within 6 days, but over 3 weeks of suppression therapy are required to abolish ovarian findings. Desensitization of the pituitary was reversible within 3 days of cessation of the treatment.

Administration of pure follicle-stimulating hormone during gonadotropin-releasing hormone agonist therapy in patients with clomiphene-resistant polycystic ovarian disease: Hormonal evaluations and clinical perspectives

Nine women with chronic anovulation caused by polycystic ovarian disease, which was unresponsive to clomiphene citrate therapy, were given a gonadotropin-releasing hormone agonist (buserelin) to induce pituitary desensitization. After 4 weeks induction of ovulation was attempted with a step-up administration of urinary follicle-stimulating hormone. Buserelin treatment was discontinued only in the presence of a positive pregnancy test result. Different responses were observed between the first and subsequent cycles. Whereas estradiol production and follicular growth were closely correlated in the first attempt, we recorded a dissociation between these two parameters of ovarian response during subsequent stimulations. Four clinical pregnancies occurred in these nine patients, and there was one abortion. This therapeutic approach can be successfully used to induce ovulation; however, prolonging pituitary suppression between treatment cycles changes the type of ovarian response and is not followed by better results.

Serum bioactive and immunoreactive follicle-stimulating hormone in prostatic cancer patients during gonadotropin-releasing hormone agonist treatment and after orchidectomy.

Serum bioactive and immunoreactive FSH levels were measured in five prostatic cancer patients during treatment for 6 months with the GnRH agonist analog buserelin (Hoechst; 600 micrograms, intranasally, 3 times per day) and for up to 12 weeks after subsequent orchidectomy. FSH bioactivity was measured using a sensitive specific in vitro granulosa cells aromatase bioassay. Before buserelin treatment, mean serum FSH bioactivity and immunoreactivity were 19.7 +/- 4.1 (+/- SE) IU/L (n = 5) and 13.7 +/- 3.8 IU/L, respectively, with a bioactivity to immunoactivity (B/I) ratio of 1.7 +/- 0.2. After the initiation of treatment with the GnRH agonist, FSH bio- and immunoactivities both transiently increased for 1-3 days. The increase in bioactivity was greater and prolonged, and the B/I ratio increased nearly 7-fold in 2 weeks. Serum FSH immunoreactivity declined to below the pretreatment level in 5 days and remained low for the rest of the treatment period. In contrast, serum FSH bioactivity did not decrease significantly below the pretreatment level during the 6-month treatment period, although the B/I ratio returned slowly toward the pretreatment value. After orchidectomy, both FSH activities increased dramatically, and the B/I ratio rose transiently from 1.5 to 7 in 2 weeks. Interestingly, serum FSH bioactivity and immunoreactivity decreased significantly (P less than 0.05) 1 day after orchidectomy in the buserelin-treated patients. In contrast, serum FSH immunoreactivity increased during the same period (P less than 0.05) in patients treated only by orchidectomy (FSH bioactivity was not measured). In conclusion, serum FSH bioactivity increases acutely more than FSH immunoreactivity after initiation of GnRH agonist treatment or orchidectomy. In the former case, serum FSH bioactivity subsequently returned to the pretreatment range. A clear decline during long term agonist treatment occurred only in serum FSH immunoreactivity, in contrast to the concomitant decline in serum LH bio- and immunoreactivities reported previously. The persistence of bioactive FSH may explain the inconsistent effects of GnRH agonist treatment on the suppression of spermatogenesis. The acute decrease in serum FSH after orchidectomy in the buserelin-treated men suggests that the testes may produce a factor that stimulates pituitary FSH secretion.