Methods for treating FSH related conditions with GnRH antagonists

Abstract

Methods for treating FSH related conditions, such as prostatic intraepithelial neoplasia, pedophilia, infertility, or vaginal bleeding, with GnRH antagonists are disclosed. The methods of the invention generally feature administering to a subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a subject, in an amount or in a formulation effective to reduce plasma FSH levels in the subject to a symptom alleviating level. In vitro fertilization and male contraceptive methods are also provided.

Description

RELATED APPLICATIONS [0001] This application is a Continuation of U.S. patent application Ser. No. 09 / 793,669 filed on Feb. 28, 2001 which, in turn, claims priority to U.S. Provisional Application No. 60 / 185,573, filed on Feb. 28, 2000; U.S. Provisional Application No. 60 / 185,574, filed on Feb. 28, 2000; U.S. Provisional Application No. 60 / 238,337, filed on Oct. 5, 2000; and U.S. Provisional Application No. 60 / 238,338, filed on Oct. 5, 2000. The entire contents of each of the foregoing applications are incorporated herein by this reference.BACKGROUND OF THE INVENTION [0002] Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are hormones released by the pituitary gland. These hormones regulate the functioning of the gonads and the production and maturation of gametes. LH and FSH are generally released by the pituitary gland upon prior release of a triggering hormone from the hypothalamus. Luteinizing hormone-releasing hormone (LHRH; also known as gonadotropin-releasing h...

AI Technical Summary

Benefits of technology

[0015] In another aspect, the invention features a method for treating prostatic intraepithelial neoplasia in a male subject, preferably a human male. The method includes administering to the subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a male subject, in an amount or in a formulation effective to reduce plasma FSH levels in the male subject, e.g., to a symptom alleviating level, thereby treating prostatic intraepithelial neoplasia in the male subject.

[0017] In yet another aspect, the invention features a method for contraception in a male subject, preferably a human male. The method includes administering to the subject an GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a male subject, in an amount or in a formulation effective to reduce plasma FSH levels in the male subject, e.g., to a symptom alleviating level, and administering testosterone to the male subject in an amount or in a formulation effective to restore libido and potency in the male subject. In one embodiment, the testosterone is administered to the male subject after the GnRH antagonist is administered. In another embodiment, the testosterone is administered to the male subject before the GnRH antagonist is administered. In yet another embodiment, the testosterone is administered to the male subject simultaneously with the GnRH antagonist.

[0021] In another aspect, the invention features a method for reducing FSH levels in a subject. The method involves administering to the subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a subject, in an amount or in a formulation effective to reduce plasma FSH levels in the subject, thereby reducing FSH levels in the subject.

Problems solved by technology

However, such GnRH superagonists initially act to stimulate LH release (and, frequently, testosterone or estrogen production) and only after prolonged treatment act to desensitize GnRH-R such that LH is no longer produced.

Additionally, each successive administration of the superagonist can cause a small LH surge (known as the “acute-on chronic” phenomenon) that again can worsen the condition.

A typical problem, however, that is frequently encountered with GnRH antagonist peptides is the occurrence of histamine-releasing activity.

This histamine-releasing activity represents a serious obstacle to the clinical use of such antagonists because histamine release results in adverse side effects such as edema and itching.

Many GnRH antagonist peptides also suffer from poor water-solubility, which complicates formulation of the antagonist for administration in vivo.

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