Long-acting Luteinizing Hormone-releasing Hormone Research Articles

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the curative treatment of PCa. This paradigm shift contributed to the combined use of androgen deprivation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data highlight the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormonal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its efficacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer.

Simple SummaryProstate cancer tumor growth is stimulated by androgens. Surgical castration or medical castration using long-acting luteinizing hormone-releasing hormone (LHRH) agonists or antagonists is the backbone of the treatments of metastatic disease. Treatment of locally advanced prostate cancer was accomplished with radiation therapy alone until multiple studies showed that combining radiation therapy with LHRH agonists results in significant survival benefit. While the goal of the use of LHRH agonists was to suppress testosterone levels during radiation, we show, through review of previous studies, that survival benefit was achieved only when LHRH was initiated during the course of radiation, and thus androgen flare during the first 1–3 weeks after the initiation of LHRH is most likely the reason for higher survival. Androgens drive tumor cells into mitosis, and mitotic death is the dominant mechanism of tumor cell kill by radiation.Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which locally advanced prostate cancer could be cured while patients maintain potency.

Administering Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer 1-6 Days Compared to More Than 14 Days after the Start of LHRH Agonist Is Associated with Better Clinical Outcomes Due to Androgen Flare.

Simple SummaryHormonal therapy with long-acting luteinizing hormone-releasing hormone (LHRH) for metastatic hormone-sensitive prostate cancer (MHSPC) results initially in testosterone flare followed by testosterone deprivation. Docetaxel is a chemotherapy that is effective against prostate cancer and specifically targets cells during cell division by stabilizing the mitotic spindle, which results in “mitotic catastrophe” and death of the dividing cancer cells. Combining LHRH and docetaxel was proved to be superior to LHRH treatment alone. Here, we show that simply by providing the first dose of docetaxel during testosterone flare, which occurs 1–6 days after LHRH initiation, patients could have better clinical outcomes, as testosterone drives specifically prostate cells into mitosis, priming them to cell kill by docetaxel.Docetaxel, when given at the beginning of androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (MHSPC), results in significantly longer overall survival than ADT alone. We aimed to investigate if the delivery of the first dose of docetaxel during the testosterone flare associated with LHRH initiation results in better clinical outcomes, as testosterone induces mitosis of prostate cancer cells, and docetaxel specifically targets cells in mitosis. We analyzed data from the CHAARTED trial which randomized MHSPC patients to ADT alone or ADT plus docetaxel. We included only patients treated with LHRH agonist and docetaxel (n = 379). The only cutoff that resulted in differences in treatment outcomes was between patients who started docetaxel 1–6 days (n = 18) compared to more than 14 days from LHRH initiation (n = 297). Actuarial median overall survival was 72 versus 57 months (p = 0.2); progression-free survival was 49 versus 17 months (p = 0.06), and freedom from castrate-resistant prostate cancer was 51 versus 18 months (p = 0.04) for patients who started docetaxel 1–6 days compared to more than 14 days from LHRH initiation, respectively. Administering docetaxel 1–6 days from the initiation of LHRH agonist for patients with MHSPC could be associated with improved clinical outcomes.

Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies.

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group.

Switching Patients With Prostate Cancer from GnRH Antagonist to Long-acting LHRH Agonist for Androgen Deprivation: Reducing Hospital Visits During the Coronavirus Pandemic.

To reduce the frequency of the need for hospital visits for patients with prostate cancer (PCa) taking androgen-deprivation therapy during the SARS-CoV-2 (COVID-19) pandemic, we switched them from gonadotropin-releasing hormone (GnRH) antagonist to a long-acting luteinizing hormone-releasing hormone (LH-RH) agonist. Here, we confirmed the efficacy and safety profile of this switching. We analyzed the medical records of 32 patients with PCa who received ADT and switched from GnRH antagonist to a long-acting LH-RH agonist during the COVID-19 pandemic, evaluating hematological and serological variables, including serum testosterone and prostate-specific antigen. Before and after the switching from GnRH antagonist to LH-RH agonist, the median serum testosterone levels were 0.22 and 0.18 ng/ml, respectively, and the median serum prostate-specific antigen levels were 0.18 and 0.11 ng/ml, respectively. No changes in the rates of flare-ups of conditions or adverse events were observed. Switching from GnRH antagonist to a long-acting LH-RH agonist appears to be a reasonable option that does not diminish efficacy or exacerbate adverse events.

Stimulation of a non-functioning pituitary macroadenoma after administration of goserelin acetate for locally advanced prostate cancer causing a sustained elevation in PSA and testosterone

Long-acting luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin, have been used for locally advanced and metastatic prostate cancer for many years and are the main forms of androgen deprivation therapy (ADT). Acting on pituitary LHRH receptors, they initially stimulate a transient rise in serum follicle stimulating hormone (FSH) and LH. Long-term administration of an LHRH analogue will eventually lead to down regulation of LHRH receptors, thus suppressing FSH and LH secretion. This in turn suppresses testosterone production hence achieving and maintaining androgen deprivation. This case highlights the potential anomaly of a sustained elevated serum testosterone in the context of newly diagnosed locally advanced prostate cancer with a co-existing pituitary macroadenoma after administration of LHRH analogues. Alternative methods of androgen deprivation must be considered in such patients.

Stimulation of a non-functioning pituitary macroadenoma after administration of goserelin acetate for locally advanced prostate cancer causing a sustained elevation in PSA and testosterone

Long-acting luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin, have been used for locally advanced and metastatic prostate cancer for many years and are the main forms of androgen deprivation therapy (ADT). Acting on pituitary LHRH receptors, they initially stimulate a transient rise in serum follicle-stimulating hormone (FSH) and LH. Long-term administration of an LHRH analogue will eventually lead to down regulation of LHRH receptors, thus suppressing FSH and LH secretion. This in turn suppresses testosterone production hence achieving and maintaining androgen deprivation. This case highlights the potential anomaly of a sustained elevated serum testosterone in the context of newly diagnosed locally advanced prostate cancer with a co-existing pituitary macroadenoma after administration of LHRH analogues. Alternative methods of androgen deprivation must be considered in such patients.

Metabolic stability of long-acting luteinizing hormone-releasing hormone antagonists

Long-acting luteinizing hormone-releasing hormone (LHRH) antagonists designed to be protease resistant consisted of a series of novel decapeptides structurally similar to LHRH. The aim of this study was to evaluate the in vitro metabolic stability of the LHRH decapeptides using pancreatin and homogenates models and identify the metabolites in rat liver homogenate for the purpose of illustrating the metabolic features of the decapeptides. The major metabolites in rat liver homogenate were identified by LC-ESI-MS(n). The half-lives of the 11 LHRH decapeptides were from 44 to 330 min in the pancreatin model. The half-lives of the five decapeptides in rat liver, kidney and lung homogenates were between 8 and 462 min. The most stable decapeptides were the LY616 and LY608 peptides with half-lives of 36 min in liver homogenate. Two major cleavage sites were found by analysing the metabolites of the LY618 peptide in rat liver homogenate, between the Pal(3)-Ser(4) and the Leu(7)-Ilys(8) peptide bonds. The major metabolites were produced via cleavages of peptide bonds at these sites, and further metabolic reactions such as hydroxylation, oxidative dechlorination, alcohol dehydration and isopropyl dealkylation were also observed.

Hypothalamic hamartoma in children

The paper presents the data of examination and treatment of children with pubertas precox (PP) resulting from hypothalamic hamartoma, a rare malformation of the brain. It analyzes the results of 27 cases that is one of the largest series of cases in the world literature. Of the greatest interest are the clinical and anatomic comparisons presented by the authors, which make it possible to define the involvement of different hypothalamic structures in the development of specific endocrine disorders. When located parahy-pothalamically, hamartomas (a peduncular type) are characterized by the symptoms of PP; when located intrahypothalamically (a sessile type), in addition to PP, there are convulsive typical symptoms (compulsive laughter attacks). At the suprahypothalamtc site, there are commonly diencephalic disorders (obesity, diabetes insipidus). The paper provides the results of surgical and hormonal treatment (the use of long-acting luteinizing hormone-releasing hormone analogues), evidence for the high efficiency of medical treatment and the low efficiency attended by a high risk of complications, surgical treatment.

Serum testosterone-based luteinizing hormone-releasing hormone agonist redosing schedule for chronic androgen ablation: a phase I assessment

Objectives. To assess the potential for using the serum testosterone level as the guide for redosing depot luteinizing hormone-releasing hormone (LHRH) agonist and to characterize the duration of castrate level testosterone after the last 22.5-mg leuprolide injection repeatedly administered for the control of prostate cancer. Methods. Informed consent was obtained from 32 men with prostate cancer (Stage T3N± M± or greater) treated with 3-month (22.5-mg) leuprolide acetate injection. Serum testosterone and prostate-specific antigen levels were obtained every 28 days beginning on the 90th day after the last 22.5-mg leuprolide injection. The duration of action was the calculated interval, in months, between the last injection and the first noncastrate serum testosterone (greater than 0.2 ng/mL) value. Results. The median duration of castrate level testosterone was 6.0 months (SE ± 0.15; upper and lower quartile 5.3 and 7.0, respectively). Prostate cancer biochemical (prostate-specific antigen) activity at enrollment and when the castrate testosterone threshold of 0.2 ng/mL was exceeded remained stable, with no significant change observed during this interval ( P = 0.52). A significant association was observed between an increasing duration of castration after LHRH agonist injection and advancing patient age ( P = 0.03) and increasing duration of hormonal therapy ( P = 0.05). Conclusions. These results suggest that using the serum testosterone level to guide in redosing of long-acting LHRH agonist may provide a novel, effective, and economical method to administer hormonal ablative therapy in patients with prostate cancer. These observations have important implications for product dosing and the design and interpretation of neoadjuvant and intermittent androgen ablative trials.

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone‐releasing hormone agonist treatments

In order to evaluate the effects of two long-acting luteinizing hormone-releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 +/- 0.9 years, bone age (BA) was 10.2 +/- 1.1 years and height was 131.9 +/- 5.0 cm. Patients in group B started therapy when CA was 7.6 +/- 0.5 years, BA 9.8 +/- 1.0 years and height 133.2 +/- 7.6 cm. The diagnosis of untreated patients (group C) was made when CA was 7.2 +/- 0.9 years, BA 9.6 +/- 2.2 years and height 130.2 +/- 8.6 cm. Both luteinizing hormone-releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 +/- 5.7 cm) was significantly higher than that of group A (153.2 +/- 5.0 cm: p < 0.05) and group C (149.6 +/- 6.3; p < 0.01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 +/- 5.7 cm) and target height (157.6 +/- 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 +/- 5.3 and 156.4 +/- 1.3 cm, respectively), but only in group C the difference was statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Pituitary-Testicular Axis Suppressionin Uteroand during the Early Neonatal Period with a Long-Acting Luteinizing Hormone-Releasing Hormone Analog on Genital Development, Somatic Growth, and Bone Density in Male Cynomolgus Monkeys in the First 6 Months of Life

The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary-testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P less than 0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH approximately A group were significantly lower than those of the placebo group throughout the first 6 months of life (P less than 0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development.

A Dose Finding Study of a Super Long-Acting Luteinizing Hormone-Releasing Hormone Analog (Leuprolide Acetate Depot, TAP-144-SR) in the Treatment of Central Precocious Puberty.

The effect of leuprolide acetate (D-Leu6-[des-Gly10-NH2]-LH-RH ethylamide acetate) for depot suspension (TAP-144-SR), a synthetic analog of luteinizing hormone-releasing hormone, was examined in three doses in 36 patients (34 girls, 2 boys) with central precocious puberty. TAP-144-SR was injected subcutaneously every four weeks for twelve weeks, and clinical symptoms and plasma and urinary levels of various hormones were followed every four weeks. Eleven girls given 10 micrograms/kg showed a significant decrease in peak plasma LH and FSH responses to LH-RH test, but basal plasma LH and FSH did not change significantly. In 13 patients (11 girls and 2 boys) given 30 micrograms/kg and 12 girls given 90 micrograms/kg, both basal and peak LH and FSH were significantly suppressed. Urinary excretion of LH decreased significantly in all groups except in the 10 micrograms/kg group. Urinary excretion of FSH did not change significantly in the 10 and 30 micrograms/kg groups, but it decreased significantly in the 90 micrograms/kg group. In girls, plasma and urinary estradiol also fell greatly, but the difference was insignificant except in the 90 micrograms/kg group. Regression of sexual characteristics was observed in almost half of the patients at the 12th week of the treatment. Side effects were minimal. A dose of more than 30 micrograms/kg of TAP-144-SR is effective in suppressing gonadotropins and causing improvement of clinical symptoms, and appears to be useful in treating children with central precocious puberty.

Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis

Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.

Differential Effects of an Luteinizing-Hormone-Releasing Hormone (LHRH) Antagonist Analogue on Lordosis Behavior Induced by LHRH and the LHRH Fragment Ac-LHRH&lt;sup&gt;5–1&lt;/sup&gt;&amp;#8304;

Both the luteinizing-hormone-releasing hormone (LHRH) decapeptide and an LHRH fragment consisting of the last 6 amino acids of the decapeptide, Ac-LHRH, have been shown to enhance lordosis behavior in ovariectomized, estradiol-benzoate treated female rats. Although the behavioral efficacy of the 2 peptides is similar, several lines of research suggest that the fragment and the decapeptide may act via different mechanisms. The present study attempted to differentiate the behavioral action of the 2 peptides by administering a long-acting LHRH antagonist analogue prior to infusion of either Ac-LHRH or LHRH. Without antagonist administration, the decapeptide and the fragment were equally effective in elevating lordotic posturing 90 min after bilateral infusion through cannulae positioned in the ventromedial nucleus of the hypothalamus (VMH). Infusion of a potent LHRH antagonist analogue [Ac-dehydro, Pro, pCl, D-Phe, DTrp]-LHRH, into the VMH significantly reduced the lordosis-to-mount ratio in animals subsequently treated with the LHRH decapeptide, but had no significant effect on lordotic behavior when the animals were subsequently infused with the Ac-LHRH fragment. The results indicate that LHRH enhancement of mating behavior is a receptor-mediated event and suggest that the Ac-LHRH fragment enhances lordotic behavior via a mechanism that is distinct from that of the LHRH decapeptide.

Delayed occurrence of an LH surge after HCG administration during ovarian stimulation with gonadotrophins: effect of LHRH treatment

Previous studies have shown the appearance of a spontaneous luteinizing hormone (LH) surge after human chorionic gonadotrophin (HCG) administration in human menopausal gonadotrophin (HMG)/HCG-stimulated menstrual cycles. In this report we investigated the effect of leuprolide acetate, a long-acting luteinizing hormone releasing hormone (LHRH) agonist, on the occurrence of these post-HCG rises in serum LH. Two groups of patients were included. Group 1: 10 patients receiving HCG as a part of an HMG/HCG protocol for induction of follicular development in an IVF/GIFT program and Group II: 10 patients treated as Group I, but receiving the LHRH agonist leuprolide acetate to inhibit gonadotrophin secretion prior to and during ovarian stimulation. In Group I, none of the patients showed a surge prior to HCG administration. However, an LH surge following HCG treatment was apparent in four patients (40%). Pregnant patients (2/10) had low mean levels (less than or equal to 2.5 mIU/ml LH) in the follicular phase and showed no LH surge after HCG. In Group II, baseline levels of serum LH were reduced significantly (mean, 1.4 +/- 0.1 mIU/ml; P less than 0.001) compared to Group I. No patient showed an LH surge either before or after HCG administration and the occurrence of pregnancy was higher (6/9 transfers) than in Group I. In spite of the differences in pregnancy rates, the combined therapy versus HMG therapy showed no significant difference in number of oocytes collected or serum oestradiol levels. This suggests that high levels of serum LH, whether prior to or after HCG administration, may have a detrimental effect on the establishment of pregnancy despite adequate follicular growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Luteinizing hormone-releasing hormone (LHRH) agonists for treatment of advanced prostatic carcinoma

The identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.

Premenstrual Exacerbations in Hepatic Porphyria: Prevention by Intermittent Administration of an LH-RH Agonist in Combination With a Gestagen

<h3>To the Editor.—</h3> Premenstrual attacks of hepatic porphyrias, in some cases occurring with each menstrual cycle, are well-known.¹Anderson et al²in 1984 reported the potential benefit of use of a luteinizing hormone-releasing hormone (LH-RH) agonist in preventing premenstrual attacks. This result was confirmed by further case reports.^3-5In all cases, the long-acting LH-RH agonist was administered continuously for months either subcutaneously or by nasal spray. We report one patient with cyclic exacerbations of acute intermittent porphyria and another patient with premenstrual exacerbations of variegate porphyria. In both patients, gynecologic evaluation revealed no abnormalities that could cause menstrual disorders. The attacks of neurological symptoms were prevented by the intermittent nasal administration of the long-acting LH-RH agonist buserelin in combination with the gestagen medroxyprogesterone acetate. The agonistic LH-RH analogue buserelin was given to both patients daily, with two hubs (2 × 150 μg) intranasally in the evening from

Effects of cyproterone acetate and a long-acting LHRH analogue on serum lipoproteins in patients with carcinoma of the prostate.

Fasting serum lipoproteins were measured in 10 untreated patients with carcinoma of the prostate (Group I), 17 patients with non-malignant urological disorders (Group II), and 12 patients on cyproterone acetate (Group III) and 5 on a long-acting luteinizing hormone-releasing hormone (LHRH) analogue (Group IV) for at least 2 months for carcinoma of the prostate. Total high-density lipoprotein (HDL) cholesterol levels were significantly lower in patients in Group III than all the other groups. Very low-density lipoprotein (VLDL) triglyceride levels were significantly higher in patients in Group III than those in Groups II and IV. These results suggest a potentially adverse effect of cyproterone acetate, but not of the long-acting LHRH analogue, on serum lipids, which is likely to be of relevance only in younger patients.

Development of pituitary gonadotropic cells in the pig fetus and the effect of luteinizing hormone-releasing hormone administration.

Pituitary gonadotropic development in fetal pigs has been studied immunocytochemically. From 50 days postcoitum (p.c.) until 90 days p.c. the volume density of luteinizing hormone (LH) immunoreactive cells increased from 0.12% to 0.61% of the glandular mass of the anterior part of the pituitary gland. From 90 to 100 days p.c. a steep increase to 4.5% was found. A single injection of long-acting luteinizing hormone-releasing hormone (LHRH) to the fetus at 75 days p.c. inhibited this developmental pattern. Pulsatile administration of LHRH agonist to fetuses from 70 to 73 days p.c. had no significant effect on the volume density of LH immunoreactive cells, whereas pulsatile administration from 70 to 80 days p.c. and from 95 to 105 days p.c. inhibited the normal increase of this parameter. It is concluded that from 70 days p.c. onwards the development of fetal gonadotropic cells can be manipulated by exogenous LHRH.