Related Experiment Videos
Comparison of various hormonal therapies for prostatic carcinoma
Abstract:
The goals of hormonal therapy for prostatic cancer are to decrease circulating plasma testosterone to castration levels; prevent a rise in or reduce circulating prolactin; and block residual androgen at the cell level. Orchiectomy is very effective but does not prevent residual adrenal androgens from being converted to dihydrotestosterone (DHT); also, it has no effect on plasma prolactin. Estrogen has no known effect on androgen-receptor concentration or DHT binding to receptor and raises plasma prolactin. It also has significant side effects. Megestrol acetate, the only antiandrogen currently available for use in the United States, has been shown to block androgen from all sources. It produces a transient reduction in plasma testosterone to levels somewhat higher than those in castrated men, and it has no effect on plasma prolactin. When used in a dose of 120 mg/day in combination with 0.5 to 1.5 mg of estradiol per day, it acts synergistically to suppress pituitary gonadotropins and maintain plasma testosterone at castration levels for periods of up to 1 year. Newer therapies being studied include flutamide, a nonsteroidal antiandrogen, and luteinizing hormone-releasing hormone (LHRH). Data on these agents are limited and comparisons with standard therapies are needed.
Insights
Hormonal therapy for prostate cancer aims to reduce testosterone and block androgens. Combining megestrol acetate with estradiol effectively suppresses testosterone to castration levels for up to one year.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Prostate cancer treatment often involves hormonal therapy to reduce androgen levels.
- Existing treatments like orchiectomy have limitations, such as not blocking adrenal androgens or affecting prolactin.
- Estrogen therapy can raise prolactin and has side effects, while megestrol acetate blocks androgens from all sources.
Purpose of the Study:
- To evaluate the efficacy of hormonal therapies in managing prostate cancer.
- To assess the role of megestrol acetate and estradiol in suppressing testosterone and blocking androgens.
- To compare current therapies with emerging treatments like flutamide and LHRH agonists.
Main Methods:
- Hormonal therapy goals include decreasing plasma testosterone to castration levels, managing prolactin, and blocking cellular androgen activity.
- Evaluation of orchiectomy, estrogen, and megestrol acetate for their effects on testosterone, prolactin, and androgen binding.
- Combination therapy of megestrol acetate (120 mg/day) with estradiol (0.5-1.5 mg/day) was studied for synergistic effects.
Main Results:
- Orchiectomy is effective but does not block adrenal androgens or affect prolactin.
- Estrogen raises prolactin and has side effects.
- Megestrol acetate, alone or with estradiol, suppresses pituitary gonadotropins, maintaining castration levels of testosterone for up to a year without affecting prolactin.
Conclusions:
- Combination therapy with megestrol acetate and estradiol offers a synergistic approach to maintain castration levels of testosterone.
- This combination effectively blocks androgens from all sources and suppresses pituitary gonadotropins.
- Further research and comparisons are needed for newer agents like flutamide and LHRH agonists.