LHRH agonists

W., and Hogan, M. P., Prolonged suppression of plasma LH levels in male rats after a single injection of an LHRH agonist in DL lactide/glycolide inicrocapsules, J. Androl., 6, 83, 1985. Tice, T. R., Meyers, W. E., Schalley, A. V., and Redding,... 

Hormonal therapies that have been studied in the treatment of primary or early breast cancer include antiestrogens, oophorectomy, ovarian irradiation, luteinizing hormone-releasing hormone (LHRH) agonists, and aromatase inhibitors. 

Outline the role of luteinizing hormone-releasing hormone (LHRH) agonists in the treatment of prostate cancer. 

Androgen ablation with a luteinizing hormone-releasing hormone (LHRH) agonist plus an antiandrogen should be used prior to radiation therapy for patients with locally advanced prostate cancer to improve outcomes over radiation therapy alone. 

Androgen ablation = serum testosterone levels less than 50 ng/mL. LHRH agonist (medical castrations or surgical are equivalent). 

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer.19 Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens.19 There are no direct comparative trials of the currently available LHRH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore, the choice between the two usually is made based on cost and patient and physician preference for a dosing schedule. 

The most common adverse effects reported with LHRH agonist therapy include a disease flare-up during the first week of therapy, hot flashes, erectile impotence, decreased libido, and injection-site reactions.19 The disease flare-up is thought to be caused by initial induction of LH and FSH by the LHRH agonist and manifests clinically as either increased bone pain or increased urinary symptoms.19 This flare reaction usually resolves after 2 weeks and has a similar onset and duration pattern for the depot LHRH products.33,34... 

Combining an LHRH agonist with flutamide demonstrated response rates greater than 90% in previously untreated patient, and the median survival was 61 months in the combination arm and 41 months in the leuprolide-alone arm in patients with minimal disease.38 However, in a comparison of goserelin with goserelin and flutamide conducted in 589 patients with 10 years of follow-up, combined androgen blockade (CAB) showed no benefit over goserelin alone.39... 

DES was once a mainstay of prostate cancer therapy. While very effective in androgen ablation, DES-treated patients experienced increased cardiovascular mortality.41 LHRH agonists, with equivalent efficacy and decreased cardiovascular toxicity, supplanted DES as a mainstay of therapy. 

Goserelin -LHRH agonist -endocrine effects -hot flashes -decreased libido -gynecomastia -impotence -nausea and vomiting (uncommon) -transient increase in bone pain... 

The major initial treatment modality for advanced prostate cancer is androgen ablation (e.g., orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonists with or without antiandrogens). After disease progression, secondary hormonal manipulations, cytotoxic chemotherapy, and supportive care are used. 

LHRH agonists provide response rates of approximately 80%, which is similar to that of orchiectomy, and have the advantage of being reversible. 

There are no comparative trials of LHRH agonists, so the choice is usually based on cost (Table 65-1) and on patient and physician preference. Leuprolide acetate is administered daily. Leuprolide depot and goserelin acetate implant can be administered monthly, or every 12 or 16 weeks. 

The most common adverse effects of LHRH agonists are disease flare-up during the first week of therapy (e.g., increased bone pain, urinary symptoms), hot flashes, erectile impotence, decreased libido, and injection-site reactions. 

Monotherapy with flutamide, bicalutamide, and nilutamide is no longer recommended due to decreased survival as compared with patients treated with LHRH agonist therapy or orchiectomy. Antiandrogens are indicated for advanced prostate cancer only when combined with an LHRH agonist (flutamide and bicalutamide]) or orchiectomy (nilutamide). In combination, antiandrogens can reduce the LHRH agonist-induced flare. 

Until definitive trials are published, it is appropriate to use either LHRH agonist monotherapy or combined androgen blockade as initial therapy for metastatic prostate cancer. 

If testosterone levels are not suppressed (i.e., greater than 20 ng/dL) after initial LHRH agonist therapy, an antiandrogen or orchiectomy may be indicated. If testosterone levels are suppressed, the disease is considered androgen independent and should be treated with palliative therapy. 

Koushik KN, Kompella UB (2004) Transport of deslorelin and LHRH agonist is vectorial and exhibits regional variation in excised bovine nasal tissue. J Pharm Pharmacol 56 861-868. 

The vaginal route is eonsidered to be suitable for the loeal applieation and absorption of therapeuties like estrogens for hormone replaeement therapy or contraception. Systemic absorption of peptide drugs sueh as LHRH agonists and ealcitonin can also be achieved [65]. 

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