Methods for treating postmenopausal women using ultra-low doses of estrogen

• US 6,692,763 B1
• Filed: 07/11/2000
• Issued: 02/17/2004
• Est. Priority Date: 11/19/1998
• Status: Expired due to Term

• Current Assignee: Bayer Healthcare Pharmaceuticals Incorporated (Bayer AG), Kaiser Foundation Health Plan Incorporated (Kaiser Permanente Inc.), Permanente Medical Group Incorporated (Kaiser Permanente Inc.), Regents of the University of California (University of California)
• Original Assignee: Berlex Laboratories Incorporated (Bayer AG), Kaiser Foundation Health Plan Incorporated (Kaiser Permanente Inc.), Permanente Medical Group Incorporated (Kaiser Permanente Inc.), Regents of the University of California (University of California)
• Inventors: Cummings, Steven R., Ellman, Herman, Ettinger, Bruce
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/554,789
• Time in Patent Office: 1,316 Days
• Field of Search: 424/443, 424/449, 424/464, 514/178
• US Class Current: 424/449
• CPC Class Codes: A61F 2013/00906 for transcutaneous or transdermal drugs application
• 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 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The present invention provides methods for treating physical conditions resulting from postmenopausel estrogen decline in a postmenopausel subject, and in particular methods for reducing the risk of osteoporotic bone fractures in a postmenopausal subject. The present invention also provides a kit for carrying out the methods of the present invention.

Claims

1. A method for treating a physical condition resulting from estrogen decline in a postmenopausal subject, said method comprising administering to said subject an amount of estrogen which is effective to produce a resulting serum level of said estrogen in said subject that is equivalent to a serum estadiol level not exceeding of between about 5 pg/ml and about 15 pg/ml, wherein:

the estrogen is administered orally, parenterally, or transdermally;

said physical condition is selected from the group consisting of osteoporosis, headaches, nausea, depression, hot flashes, decrease in bone mineral density, and increased risk or incidence of bone fracture; and

the resulting serum level of the estrogen is responsive to the administering of the estrogen.

2. The method of claim 1, wherein said physical condition is selected from the group consisting of postmenopausal estrogen decline, increased risk of osteoporotic bone fracture due to postmenopausal osteoporosis, and loss of bone mineral density.

3. The method of claim 1, wherein said amount of estrogen which is administered is effective to produce a serum level of said estrogen equivalent to a serum estradiol level in said subject of between about 5 pg/ml and about 10 pg/ml.

4. The method of claim 1, wherein said estrogen is estradiol.

5. The method of claim 4, comprising orally administering said amount of estrogen.

6. The method of claim 5, wherein said amount of estrogen administered is less than 0.5 mg/day.

7. The method of claim 5, wherein said amount of estrogen administered is between 0.1-0.25 mg/day.

8. The method of claim 4, comprising parenterally administering said amount of estrogen.

9. The method of claim 8, wherein said amount of estrogen administered is less than about 20 μ

g/day.

10. The method of claim 8, wherein said amount of estrogen administered is between 5-15 μ

g/day.

11. The method of claim 8, wherein said amount of estrogen administered is about 10 μ

g/day.

12. The method of claim 4, comprising transdermally administering said amount of estrogen.

13. The method of claim 12, wherein said amount of estrogen administered is not more than about 15 μ

g per day.

14. The method of claim 12, wherein said amount of estrogen administered is between about 5 μ

g and about 15 μ

g per day.

15. A kit for use by a consumer afflicted with or susceptible to physical conditions resulting from postmenopausal estrogen decline, said kit comprising:

a) a transdermal patch for transdermally administering an estrogen in an amount that is equivalent to less than about 15 μ

g of estradiol per day; and

b) instructions describing a method of using the transdermal patch to reduce the risk of osteoporotic bone fracture in said consumer.

16. A method for treating a physical condition resulting from estrogen decline in a postmenopausal subject, said method comprising administering transdermally an estrogen in an amount that is equivalent to less than about 20 μ

g of estradiol per day to said subject, in the substantial absence of exogenous progestin, wherein serum level of said estrogen in said subject is equivalent to a serum estradiol level of between about 5 pg/ml and about 15 pg/ml, and wherein said physical condition is selected from the group consisting of osteoporosis, headaches, nausea, depression, hot flashes, decrease in bone mineral density, and increased risk or incidence of bone fracture.

17. The method of claim 16, wherein said physical conditions are selected from the group of postmenopausal estrogen decline, increased risk of osteoporotic bone fracture due to postmenopausal osteoporosis, and loss of bone mineral density.

18. The method of claim 16, wherein said administration is prior to hysterectomy of said subject.

19. The method of claim 16, wherein said estrogen is estradiol.

20. The method of claim 19, further comprising the step of testing the serum estradiol level of the subject and determining that the serum estradiol level of the subject to be treated is normal for postmenopausal women in the same age group as the subject.

21. The method of claim 19, wherein said amount of estrogen administered is between about 5 μ

g and about 15 μ

g per day.

22. The method of claim 19, wherein said amount of estrogen administered is about 10 μ

g per day.

23. The method of claim 19, wherein said amount of estrogen administered is about 15 μ

g per day.