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

• US 20050250750A1
• Filed: 09/03/2003
• Published: 11/10/2005
• Est. Priority Date: 11/19/1998
• Status: Abandoned Application

• Current 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)
• 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
• Application Number:
  US10/655,481
• Publication Number:
  US 20050250750A1
• Time in Patent Office: Days
• US Class Current: 514/182
• 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 postmenopausal estrogen decline in a postmenopausal subject, and in particular methods for reducing the risk of osteoporotic bone fractures in a postmenopausal subject. The present invention also provides a kit useful for carrying out the methods of the present invention.

Claims

1. A pharmaceutical composition for treating physical conditions resulting from estrogen decline in a postmenopausal subject, the composition comprising estrogen in an amount effective to produce a serum level of the estrogen in the subject that is equivalent to a serum estradiol level of between 5 pg/ml and about 15 pg/ml.

2. The composition of claim 1, wherein the physical condition is selected from the group consisting of postmenopausal estrogen decline, osteoporosis, headaches, nausea, depression, hot flashes, increased risk or incidence of bone fracture due to postmenopausal osteoporosis, and loss of bone mineral density.

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

4. The composition of claim 1, wherein the estrogen is estradiol.

5. The composition of claim 1, wherein the estrogen is present in the substantial absence of exogenous progestin.

6. The composition of claim 1, the composition comprising the estrogen in an amount that provides for a dosage of between about 0.1 and about 0.25 mg of estrogen per day.

7. The composition of claim 1, the composition comprising the estrogen in an amount that provides for a dosage of less than about 5 μ

g of estrogen per day.

8. The composition of claim 1, the composition comprising the estrogen in an amount that provides for a dosage of less than about 20 μ

g of estrogen per day.

9. The composition of claim 1, the composition comprising the estrogen in an amount that provides for a dosage of between about 5 and about 15 μ

g of estrogen per day.

10. The composition of claim 1, the composition comprising the estrogen in an amount that provides for a dosage of about 10 μ

g of estrogen per day.

11. The composition of claim 1, wherein the composition is present in an oral formulation selected from the group consisting of one or more capsules, one or more cachets, one or more lozenges, one or more tablets, a powder, a granule, a solution, a dispersion, a suspension in an aqueous liquid, and a suspension in a non-aqueous liquid.

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

a) a transdermal patch for transdermally administering an estrogen in an amount that is equivalent to between about 0.1 and about 0.25 mg of estradiol per day; and

b) instructions describing a method of using the transdermal patch to treat or inhibit a physical condition resulting from estrogen decline in the consumer.

13. A kit for use by a consumer afflicted with or susceptible to a physical condition 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 20 μ

g of estradiol per day; and

b) instructions describing a method of using the transdermal patch to treat or inhibit a physical condition resulting from estrogen decline in the consumer.

14. The kit of claim 13, wherein the kit comprises a transdermal patch for transdermally administering an estrogen in an amount that is equivalent to less than about 5 μ

g of estradiol per day.

15. The kit of claim 13, wherein the kit comprises a transdermal patch for transdermally administering an estrogen in an amount that is equivalent to between about 5 and about 15 μ

g of estradiol per day.

16. The kit of claim 13, wherein the kit comprises 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.

17. The kit of claim 13, wherein the kit comprises a transdermal patch for transdermally administering an estrogen in an amount that is equivalent to about 10 μ

g of estradiol per day.

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

a) a transdermal patch for transdermally administering an estrogen, the transdermal patch comprising the estrogen in an amount effective to produce a serum level of the estrogen in the subject that is equivalent to a serum estradiol level of between 5 pg/ml and about 15 pg/ml; and

b) instructions describing a method of using the transdermal patch to treat or inhibit a physical condition resulting from estrogen decline in the consumer.

19. 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 estradiol level 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;

the resulting serum level of the estrogen is responsive to the administering of the estrogen; and

the administration of the estrogen does not substantially increase the risk of endometrial or breast cancer in the postmenopausal subject.

20. The method of claim 19, 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.

21. The method of claim 19, 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.