Methods for preventing and treating osteoporosis with low dose non-masculinizing androgenic compounds

• US 5,846,960 A
• Filed: 06/07/1995
• Issued: 12/08/1998
• Est. Priority Date: 06/28/1991
• Status: Expired due to Fees

• Current Assignee: Endorecherche
• Original Assignee: Endorecherche
• Inventors: Labrie, Fernand
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/477,172
• Time in Patent Office: 1,280 Days
• Field of Search: 514/169, 514/170, 514/177, 514/179
• US Class Current: 514/169
• 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 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

A method of treatment or prevention of breast and endometrial cancer, osteoporosis and endometriosis in susceptible warm-blooded animals comprising administering a low dose of a progestin or other steroid derivative having androgenic activity and low masculinizing activity. Pharmaceutical compositions useful for such treatment and pharmaceutical kits containing such compositions are disclosed. An in vitro assay permitting specific measurements of androgenic activity of potentially useful compounds is also disclosed.

Claims

1. A method for treating osteoporosis in a patient in need of such treatment, comprising administering to said patient at least one androgenic steroid having a Ki value for the androgen receptor of less than about 2×

10^-8 M and an androgen receptor-mediated inhibitory effect on the growth of human breast cancer ZR-75-1 cells which reaches half-maximal value at a concentration below 3.0 nanomoles per liter and no visible masculinizing activity wherein said androgenic steroid is administered at a dosage sufficiently low to maintain a cumulative androgenic steroid serum concentration between 1 and 50 nanomoles per liter for a period of at least 30 days.

2. The method of claim 1, wherein said cumulative serum concentration is maintained between about 1 and 25 nanomoles per liter.

3. The method of claim 1, wherein said cumulative serum concentration is maintained between 1 and about 15 nanomoles per liter.

4. The method of claim 1, wherein said cumulative serum concentration is maintained between 1 and 10 nanomoles per liter.

5. The method of claim 1, wherein said androgenic steroid(s) is(are) administered together with a pharmaceutically acceptable diluent or carrier in a dosage which delivers less than 25 milligrams of such androgenic steroid(s) per 50 kilograms of body weight per day.

6. The method of claim 5, wherein said androgenic steroid(s) is(are) administered in an amount between about 1 and about 10 milligrams of said androgenic steroid(s) per 50 kilograms of body weight per day.

7. The method of claim 5, wherein said androgenic steroid(s) is(are) administered in an amount between about 3 and about 7 milligrams of said androgenic steroid(s) per 50 kilograms of body weight per day.

8. The method of claim 1, wherein at least one androgenic steroid is a synthetic progestin.

9. The method of claim 1, wherein at least one androgenic steroid is an anabolic steroid.

10. The method of claim 1, wherein at least one androgenic steroid is medroxyprogesterone acetate (17α

-acetoxy6α

-methyl progesterone).

11. The method of claim 7, wherein at least one androgenic steroid is medroxyprogesterone acetate (17α

-acetoxy-6α

-methyl progesterone).

12. The method of claim 11 further comprising administering an effective amount of estrogen for prevention or reduction of menopausal symptoms selected from the group consisting of vasomotor symptoms, urogenital atrophy, bone loss, irritability, insomnia, anxiety and fatigue.

13. The method of claim 2 further comprising administering an effective amount of estrogen for prevention or reduction of menopausal symptoms selected from the group consisting of vasomotor symptoms, urogenital atrophy, bone loss, irritability, insomnia, anxiety and fatigue.

14. The method of claim 3 further comprising administering an effective amount of estrogen for prevention or reduction of menopausal symptoms selected from the group consisting of vasomotor symptoms, urogenital atrophy, bone loss, irritability, insomnia, anxiety and fatigue.

15. The method of claim 4 further comprising administering an effective amount of estrogen for prevention or reduction of menopausal symptoms selected from the group consisting of vasomotor symptoms, urogenital atrophy, bone loss, irritability, insomnia, anxiety and fatigue.

16. The method of claim 1 where osteoporosis is treated in a human patient.

17. The method of claim 16, wherein said cumulative serum concentration is maintained between about 1 and 25 nanomoles per liter.

18. The method of claim 16, wherein said cumulative serum concentration is maintained between 1 and about 15 nanomoles per liter.

19. The method of claim 16, wherein said cumulative serum concentration is maintained between 1 and 10 nanomoles per liter.

20. The method of claim 16 wherein said androgenic compound is medroxyprogesterone acetate.

21. The method of claim 16 wherein said androgenic compound is megestrol acetate.

22. The method of claim 16 wherein said androgenic compound is Gestodene.

23. A method for treating osteoporosis in a patient in need of such treatment comprising administering to said patient medroxyprogesterone acetate at a dosage sufficiently low to maintain serum concentration of said medroxyprogesterone acetate between 1 and 50 nanomoles per liter for at least 30 days.

24. The method of claim 23, wherein said dosage is between 1 and 10 milligrams per 50 kilograms of body weight per day.

25. A method for treating osteoporosis in a patient in need of such treatment comprising administering megestrol acetate to said patient at a dosage sufficiently low to maintain serum concentration of said megestrol acetate between 1 and 50 nanomoles per liter for at least 30 days.

26. The method of claim 25, wherein said dosage is between 1 and 10 milligrams per 50 kilograms of body weight per day.