Administration of non-oral androgenic steroids to women

• US 6,583,129 B1
• Filed: 06/09/2000
• Issued: 06/24/2003
• Est. Priority Date: 06/11/1999
• Status: Expired due to Term

• Current Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Original Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Mazer, Norman A., Rosario-Jansen, Theresa
• Primary Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US09/591,141
• Time in Patent Office: 1,110 Days
• Field of Search: 424/400, 514/167, 514/169, 514/170, 514/172, 514/177, 514/178, 514/182
• US Class Current: 514/167
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/5685 having an oxo group in position 17, e.g. androsterone
• 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: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/26 Androgens
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The present invention provides compositions, methods, and kits for improving health in a woman having elevated SHBG levels, or who is receiving oral estrogen supplementation, by non-orally administering an effective amount of an androgenic steroid. Further, the present invention provides compositions, methods, and kits for coadministering an effective amount of an orally administered estrogen and an effective amount of a non-orally administered androgenic steroid for women in need of estrogen supplementation.

Claims

1. A method of improving health in a woman having an elevated or substantially elevated level of sex hormone binding globulin (SHBG) comprising non-orally administering to said woman an androgenic steroid in an amount sufficient to provide a therapeutic effect in the presence of elevated or substantially elevated SHBG levels.

2. The method of claim 1, wherein the woman is receiving oral estrogen supplementation.

3. The method of claim 2, wherein the oral estrogen and the non-oral androgenic steroid are coadministered.

4. The method of claim 2, wherein said androgenic steroid is a member selected from the group consisting of:

testosterone, methyltestosterone, androstenedione, adrenosterone, dehydroepiandrosterone, oxymetholone, fluoxymesterone, methandrostenolone, testolactone, pregnenolone, 17α

-methylnortestosterone, norethandrolone, dihydrotestosterone, danazol, oxymetholone, androsterone, nandrolone, stanozolol, ethylestrenol, oxandrolone, bolasterone and mesterolone, testosterone propionate, testosterone cypionate, testosterone phenylacetate, testosterone enanthate, testosterone acetate, testosterone buciclate, testosterone heptanoate, testosterone decanoate, testosterone caprate, testosterone isocaprate, and isomers thereof, and a combination thereof.

5. The method of claim 2, wherein said androgenic steroid is a member selected from the group consisting of:

testosterone, dihydrotestosterone, methyltestosterone, and isomers thereof, and a combination thereof.

6. The method of claim 2, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a total testosterone serum level of from about 15 to about 1000 ng/dl.

7. The method of claim 6, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a total testosterone serum level of from about 85 to about 1000 ng/dl.

8. The method of claim 6, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a total testosterone serum level of from about 100 to about 1000 ng/dl.

9. The method of claim 2, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a free testosterone serum level of from about 0.5 to about 30 pg/ml.

10. The method of claim 9, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a free testosterone serum level of from about 1 to about 15 pg/mL.

11. The method of claim 9, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a free testosterone serum level of from about 3 to about 10 pg/ml.

12. The method of claim 9, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a free testosterone serum level of about 1 to about 7 pg/ml.

13. The method of claim 2, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a bioavailable testosterone serum level of from about 1 to about 70 ng/dl.

14. The method of claim 13, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a bioavailable testosterone serum level of from about 2 to about 35 ng/dl.

15. The method of claim 13, wherein said androgenic steroid dosage is sufficient to achieve a therapeutic effect equivalent to a bioavailable testosterone serum level of from about 2 to about 13 ng/dl.

16. The method of claim 2, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a testosterone dosage of at least about 50 mcg/day.

17. The method of claim 16, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a testosterone dosage of from about 75 to about 3000 mcg/day.

18. The method of claim 16, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a testosterone dosage of from about 500 to about 2500 mcg/day.

19. The method of claim 16, wherein said androgenic steroid is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a testosterone dosage of from about 550 to about 2000 mcg/day.

20. The method of claim 2, wherein said non-oral administration is topical administration, or parenteral administration, or a combination thereof.

21. The method of claim 20, wherein said parenteral administration is intramuscular injection, or subcutaneous implantation, or a combination thereof.

22. The method of claim 20, wherein said topical administration is transdermal, transmucosal, or sublingual, or a combination thereof.

23. The method of claim 2, wherein said improved health is manifest by restoration, enhancement, or improvement of a characteristic selected from the group consisting of:

sexual desire, stimulation to sexual organs, ability to achieve orgasm, pleasure in sexual activity, frequency of sexual activity, vital energy, sense of well-being, mood and sense of emotional well being, shyness, cognitive abilities, muscle mass and function, body composition, bone mineral density, skin and hair condition, pubic hair, urogenital atrophy, vaginal dryness, dry eyes, health in autoimmune conditions, vasomotor instability, breast tenderness, symptoms of premenstrual syndrome, and a combination thereof.

24. The method of claim 2, wherein said estrogen is administered in a dosage sufficient to achieve a therapeutic effect equivalent to a conjugated equine estrogen dosage of from about 0.2 to about 3.0 mg/day.

25. The method of claim 2, wherein said orally administered estrogen is a member selected from the group consisting of:

17β

-estradiol, 17α

-estradiol, conjugated equine estrogen, esterified estrogen, micronized estradiol, sodium estrogen sulfate, ethinyl estradiol, estrone, tibolone, selective estrogen receptor modulator (SERM), phytoestrogen, and isomers thereof, and a combination thereof.

26. The method of claim 2, wherein said orally administered estrogen is a conjugated equine estrogen.

27. The method of claim 2, wherein said orally administered estrogen is an esterified estrogen.

28. The method of claim 2, wherein said orally administered estrogen is micronized estradiol.

29. The method of claim 2, further comprising administering an effective amount of a progestin sufficient to provide endometrial safety.

30. The method of claim 2, further comprising administering an amount of progestin sufficient to provide effective contraception.