Treatment of conditions relating to hormone deficiencies by administration of progestins

• US 7,427,609 B2
• Filed: 10/03/2003
• Issued: 09/23/2008
• Est. Priority Date: 05/16/2001
• Status: Expired due to Fees

• Current Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Barr Laboratories Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Leonard, Thomas W.
• Primary Examiner(s): Henley, III; Raymond J
• Application Number:
  US10/678,828
• Publication Number:
  US 20040072808A1
• Time in Patent Office: 1,817 Days
• Field of Search: None
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/566 having an oxo group in position 17, e.g. estrone
• CPC Class Codes: A61K 31/569 substituted in position 17 alpha, e.g. ethisterone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

The present invention includes methods for preventing endometrial hyperplasia associated with estrogen therapy through the administration of a progestin agent. The methods presented may include starting the administration of a progestin agent at a high dose, and then lowering the dose.

Claims

1. A method of treating vasomotor symptoms comprising:

administering continuously and uninterruptedly a dose of a therapeutic amount of an estrogenic compound to a subject;

administering continuously and uninterruptedly a dose of a therapeutic amount of a progestin agent to a subject for about 7 to about 120 days; and

administering continuously and uninterruptedly a second dose of a therapeutic amount of a progestin agent at a later time period to the subject for at least about two weeks, said second dose comprising a lower dosage of said therapeutic amount of a progestin agent than said first dose.

2. The method according to claim 1, wherein said progestin agent is selected from the group consisting of dl-norgestrel, norethindrone (norethisterone), norethindrone (norethisterone) acetate, ethynodiol diacetate, dydrogesterone, medroxyprogesterone acetate, norethynodrel, allylestrenol, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, desogestrel, levonorgestrel, hydroxyprogesterone caproate, 19-nortestosterone, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, trimegestone, gestodene, normegestrel acetate, progesterone, 5α

-pregnan-3β

, 20β

-diol sulfate, 5α

-pregnan-3β

-ol-20-one, 16,5α

-pregnen-3β

-ol-20-one and 4-pregnen-20β

-ol-3-one-20-sulfate.

3. The method according to claim 1, wherein said first dose comprises an equivalent of 0.5 to 40 mg of a progestin agent, based on equivalent oral doses to megestrol acetate.

4. The method according to claim 1, wherein said first dose comprises an equivalent of 2 to 20 mg of a progestin agent, based on equivalent oral doses to megestrol acetate.

5. The method according to claim 1, wherein said second dose comprises an equivalent of 0.025 to 10 mg of a progestin agent, based on equivalent oral doses to megestrol acetate.

6. The method according to claim 1, wherein said estrogenic compound is a conjugated estrogen.

7. The method according to claim 1, wherein said estrogenic compound is selected from the group consisting of estrone, 17α

-estradiol, 17β

-estradiol, equilin, 17α

-dihydroequilin, 17β

-dihydroequilin, equilenin, 17α

-dihydroequilen in, 17β

-dihydroequilenin, Δ

^8,9-dehydroestrone, 17α

Δ

^8,9-dehydroestradiol, 17β

Δ

^8,9-dehydroestradiol, 6-OH equilenin, 6-OH 17α

-dihydroequilenin, ethinyl estradiol, estradiol valerate, 6-OH 17β

-dihydroequilenin, and mixtures, conjugates and salts thereof.

8. The method according to claim 1, wherein said second dose of a progestin agent is administered after therapy of the vasomotor symptoms has been effectively established.

9. The method according to claim 1, wherein said second dose of a progestin agent is administered between 1 week and 12 weeks after the first dose of a progestin agent.

10. The method according to claim 1, wherein said second dose of a progestin agent is administered between 2 weeks and 8 weeks after the first dose of a progestin agent.

11. The method according claim 1, wherein said first dose is continuously and uninterruptedly administered to said subject for a predetermined period of time and then said second dose is continuously and uninterruptedly administered to said subject.

12. The method according to claim 1, comprising:

administering a third dose of a therapeutic amount of a progestin agent at a later time period to the subject than that of said second dose, said third dose comprising a lower dosage of said therapeutic amount of a progestin agent than said second dose.

13. The method according to claim 1, wherein said subject is human.

14. A method for treating vasomotor symptoms in a subject afflicted therewith, comprising administering a dose of a therapeutic amount of an estrogenic compound to a subject;

administering a progestin agent to said subject for at least two cycles of a cyclical dosing schedule, wherein the first cycle comprises a dosing period of at least one week, in which the progestin agent is administered daily, at a dose of an equivalent of 8 to 40 mg/day of oral megestrol acetate, followed by at least one second cycle comprising a dosing period of at least about two weeks in which a progestin agent is administered daily, at a dose of an equivalent of 4 to 20 mg/day of oral megestrol acetate.