Methods and formulations for use in treating oophorectomized women

• US 5,340,586 A
• Filed: 05/17/1993
• Issued: 08/23/1994
• Est. Priority Date: 04/12/1991
• Status: Expired due to Term

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Pike, Malcolm C., Spicer, Darcy V.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/062,886
• Time in Patent Office: 463 Days
• Field of Search: 424/422, 424/423, 424/424, 424/426, 424/430, 424/432, 424/433, 424/484, 424/485, 424/486, 424/487, 424/488, 424/489, 424/490, 424/496, 424/497, 424/DIG. 14, 514/2, 514/12, 514/21, 514/800, 514/841, 514/842, 514/843, 530/313, 530/850, 530/853, 128/830, 128/832, 128/833
• US Class Current: 424/426
• 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 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives

Abstract

Compositions and methods which are effective to prevent symptoms of loss of ovarian function (e.g., in oophorectomized women) over a period of time are described, consisting essentially of an effective amount of an estrogenic composition and an effective amount of an androgenic composition. The levels of estrogens and androgens employed are sufficient to reduce bone mineral density loss and minimize other side effects observed after oophorectomy, and at such low doses as to minimize any adverse impact on the patient'"'"'s long-term prognosis or (in the case of testosterone) result in additional side effects.

Claims

1. A composition for preventing symptoms and signs of loss of ovarian function in oophorectomized women over a period of time consisting essentially of:

a slow-release formulation of an estrogenic composition which maintains serum level of said estrogenic composition over said period of time at a level effective to prevent symptoms and signs of estrogen deficiency, wherein said serum level of said estrogenic composition is equivalent to serum estradiol levels in the range of about 15 to about 50 pg/ml; and

a slow-release formulation of an androgenic hormone which increases serum level of said androgenic hormone over said period of time to a level not exceeding a normal premenopausal level for a patient, wherein said serum level of said androgenic composition is equivalent to serum testosterone levels in the range of about 20 to about 80 ng/dl.

2. A composition according to claim 1, wherein said estrogenic composition is selected from the group consisting of estradiol, estradiol benzoate, estradiol cypionate, estradiol valerate, estrone, diethylstilbestrol, piperazine estrone sulfate, ethinyl estradiol, mestranol, polyestradiol phosphate, estriol, estriol hemisuccinate, quinestrol, estropipate, pinestrol, estrone potassium sulfate, equilelinin, equilelinin sulfate, estetrol and mixtures of two or more thereof.

3. A composition according to claim 1, wherein said androgenic hormone is selected from the group consisting of testosterone, androstenedione, dihydrotestosterone, testosterone propionate, testosterone enanthate, testosterone cypionate, methyltestosterone, danazol, dromostanolone propionate, ethylestrenol, methandriol, nandrolone decanoate, nandrolone phenpropionate, oxandrolone, oxymethalone, stanozolol and testolactone.

4. A composition according to claim 1, wherein said period of time is about 3 days to about five years.

5. A composition according to claim 4, wherein said period of time is about three months to about four months.

6. A composition according to claim 1, for administration by a subcutaneous, intramuscular, vaginal or transdermal route.

7. A composition according to claim 1, in the form of an implantable device.

8. A composition according to claim 1, wherein said serum level of said estrogenic composition is equivalent to serum estradiol levels in the range of about 20 to about 35 pg/ml.

9. A method for preventing symptoms and signs of loss of ovarian function in oophorectomized women over a period of time, comprising:

administering an estrogenic composition in an amount effective to maintain serum level of said estrogenic composition over said period of time at a level effective to prevent symptoms and signs of estrogen deficiency, said serum level of said estrogenic composition being equivalent to serum estradiol levels in the range of about 15 to about 50 pg/ml; and

simultaneously administering an androgenic composition over said period of time in an amount effective to increase effective androgen level to a level not exceeding a normal premenopausal level for a patient, wherein said serum level of said androgenic composition is equivalent to serum testosterone levels in the range of about 20 to about 80 ng/dl.

10. A method according to claim 9, wherein said period of time is about 3 days to about five years.

11. A method according to claim 10, wherein said period of time is about three months to about four months.

12. A method according to claim 9, wherein said estrogenic composition is selected from the group consisting of estradiol, estradiol benzoate, estradiol cypionate, estradiol valerate, estrone, diethylstilbestrol, piperazine estrone sulfate, ethinyl estradiol, mestranol, polyestradiol phosphate, estriol, estriol hemisuccinate, quinestrol, estropipate, pinestrol, estrone potassium sulfate, equilelinin, equilelinin sulfate, estetrol and mixtures of two or more thereof.

13. A method according to claim 9, wherein said androgenic hormone is selected from the group consisting of testosterone, androstenedione, dihydrotestosterone, testosterone propionate, testosterone enanthate, testosterone cypionate, methyltestosterone, danazol, dromostanolone propionate, ethylestrenol, methandriol, nandrolone decanoate, nandrolone phenpropionate, oxandrolone, oxymethalone, stanozolol and testolactone.

14. A method according to claim 9, wherein said serum level of said estrogenic composition is equivalent to serum estradiol levels in the range of about 20 to about 35 pg/ml.