Pharmaceutical compositions

Abstract

Novel methods for treating or reducing the likelihood of acquiring symptoms or diseases due to the menopause, in postmenopausal women, particularly osteoporosis, vaginal atrophy and dryness, hypogonadism, diminished libido, skin atrophy, connective tissue disease, urinary incontinence, breast, endometrial, ovarian and uterine cancers, hot flashes, loss of muscle mass, insulin resistance, fatigue, loss of energy, aging, physical symptoms of menopause, in susceptible warm-blooded animals including humans involving administration of a sex steroid precursor are disclosed. Said method comprising novel ways of administering and dosing dehydroepiandrosterone (DHEA) in order to take advantage of positive androgenic effects in the vaginal layers lamina propia and/or the layer muscularis, without undesirably causing systemic estrogenic effects in order to avoid the risk of breast and uterine cancer. Pharmaceutical compositions for delivery of active ingredient(s) useful to the invention are also disclosed.

1 . A method of treating and/or reducing the likelihood of acquiring symptoms or diseases due to the menopause, in postmenopausal women, said method comprising administering a sex steroid precursor selected from the group consisting of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androst-5-ene-3β,17β-diol, and 4-androsten-3,17-dione to a patient in need of said treatment wherein the said sex steroid precursor is administered at a therapeutic amount which increases the level of circulating androgen metabolites without increasing the circulating level of estradiol above the values found in normal postmenopausal women in order to avoid the risk of breast and uterine cancer. 
     
     
         2 . The method of  claim 1  wherein the sex steroid precursor is administered on the skin. 
     
     
         3 . The method of  claim 1  wherein the sex steroid precursor is administered intravaginally. 
     
     
         4 . The method of  claim 1  wherein the sex steroid precursor is administered orally. 
     
     
         5 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is 200 mg per day or less. 
     
     
         6 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is 100 mg per day or less. 
     
     
         7 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is 30 mg per day or less. 
     
     
         8 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is 15 mg per day or less. 
     
     
         9 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is 50 mg per day or less. 
     
     
         10 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is 25 mg per day or less. 
     
     
         11 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is 13 mg per day or less. 
     
     
         12 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is 6.5 mg per day or less. 
     
     
         13 . The method of  claim 4  wherein the therapeutic amount of sex steroid precursor is 200 mg per day or less. 
     
     
         14 . The method of  claim 4  wherein the therapeutic amount of sex steroid precursor is 100 mg per day or less. 
     
     
         15 . The method of  claim 4  wherein the therapeutic amount of sex steroid precursor is 50 mg per day or less. 
     
     
         16 . The method of  claim 1  wherein the average 24 h-level of circulating estradiol is below 10 μg/mL. 
     
     
         17 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is administered by means of a topical formulation selected from the group consisting of cream, lotion, gel, ointment, sustained release patch, and the like, and wherein said formulation contains 10% of sex steroid precursor or less. 
     
     
         18 . The method of  claim 2  wherein the therapeutic amount of sex steroid precursor is administered by means of a topical formulation selected from the group consisting of cream, lotion, gel, ointment, sustained release patch, and the like, and wherein said formulation contains 2.0% of sex steroid precursor or less. 
     
     
         19 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is administered by means of a intravaginal formulation selected from the group consisting of cream, lotion, gel, ointment, ovule, suppository, ring, and the like, and wherein said formulation contains 10% of sex steroid precursor or less. 
     
     
         20 . The method of  claim 3  wherein the therapeutic amount of sex steroid precursor is administered by means of a intravaginal formulation selected from the group consisting of cream, lotion, gel, ointment, ovule, suppository, ring, and the like, and wherein said formulation contains 2.0% of sex steroid precursor or less. 
     
     
         21 . The method of  claim 4  wherein the therapeutic amount of sex steroid precursor is administered by means of an oral formulation selected from the group consisting of capsules, plug capsules, pills, tablets, syrups. 
     
     
         22 . The method of  claim 1 , further comprising administering as part of a combination therapy, a therapeutically effective amount of a Selective Estrogen Receptor Modulator. 
     
     
         23 . A method of treating and/or reducing the likelihood of acquiring symptoms or diseases due to the menopause, in postmenopausal women, said method comprising administering a sex steroid precursor selected from the group consisting of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androst-5-ene-3β,17β-diol, and 4-androsten-3,17-dione to a patient in need of said treatment wherein the said sex steroid precursor is administered at a therapeutic amount which increases the level of circulating androgen metabolites and further comprising administering as part of a combination therapy, a therapeutically effective amount of a Selective Estrogen Receptor Modulator in order to decrease the risk of breast and uterine cancer normally present in postmenauposal women and to prevent bone loss, fat accumulation and diabetes type 2. 
     
     
         24 . The method of  claim 23  wherein the Selective Estrogen Receptor Modulator has the following chemical structure. 
       
         
           
           
               
               
           
         
       
     
     
         25 . The method of  claim 1  wherein the symptoms or diseases due to the menopause are selected from the group of diseases consisting of osteoporosis, vaginal atrophy, vulvo-vaginal dryness, hypogonadism, diminished libido, skin atrophy, connective tissue disease, urinary incontinence, loss of muscle mass, insulin resistance, fatigue, loss of energy, aging, and physical symptoms and signs of menopause. 
     
     
         26 - 38 . (canceled) 
     
     
         39 . The method of  claim 23  wherein the symptoms or diseases due to the menopause are selected from the group of diseases consisting of osteoporosis, vaginal atrophy, vulvo-vaginal dryness, hypogonadism, diminished libido, skin atrophy, connective tissue disease, urinary incontinence, loss of muscle mass, insulin resistance, fatigue, loss of energy, aging, and physical symptoms and signs of menopause.