Therapeutic applications of estrogenic carboxylic acids

Abstract

Provided are methods employing estrogenic compounds for: repressing weight gain or reducing weight in male patients; treating or preventing prostate cancer and peri- or post-menopausal symptoms; treating estrogen-responsive conditions that no longer respond to treatment with conventional steroidal estrogens; treating or preventing estrogen-responsive uterine cancer, breast cancer, and ovarian follicle atresia; inducing ovulation to increase fertility; oral contraception; treating or preventing diseases or conditions caused or prolonged by free radicals; treating or preventing cardiovascular disease, hyperlipidemia or hypercholesterolemia, and hyperglycemia; improving body fat distribution; and treating or preventing Alzheimer's disease, osteoporosis, and pattern baldness. Also provided are methods for treating or preventing prostatic diseases including benign prostate hyperplasia and other related conditions, androgen-responsive pathological conditions in males, and methods for male birth control and chemical castration, employing estrogenic carboxylic acids.

What is claimed is:  
     
         1 . A method for repressing weight gain or reducing weight in a male patient, comprising administering (+)-Z-bisdehydrodoisynolic acid in a dosage effective to repress weight gain or reduce weight to a male patient suffering from, or disposed to, weight gain.  
     
     
         2 . The method of  claim 1 , wherein said dosage is in the range of from about 0.1 μg/kg/day to about 100 mg/kg/day.  
     
     
         3 . A method for treating or preventing a disease, condition, or symptom selected from the group consisting of prostatic disease, peri- or post-menopausal symptoms, an estrogen-responsive condition that no longer responds to treatment with conventional steroidal estrogens, an estrogen-responsive uterine cancer, breast cancer, ovarian follicle atresia, a disease or condition caused or prolonged by free radicals, cardiovascular disease, hyperlipidemia, hypercholesterolemia, hyperglycemia, Alzheimer's disease and pattern baldness, comprising administering an estrogenic carboxylic acid in a dosage effective to treat or prevent said disease, symptom, or condition to a patient suffering from, or disposed to, said disease, symptom, or condition.  
     
     
         4 . The method of  claim 3 , wherein said estrogenic carboxylic acid is selected from the group consisting of a doisynolic acid, an allenolic acid, a phenylcyclohexenecarboxylic acid, a hydroxyphenylcyclohexenecarboxylic acid, a phenylcyclohexanecarboxylic acid, a hydroxyphenylcyclohexanecarboxylic acid, a hydroxytetrahydroanthracenecarboxylic acid, and a tetrahyroanthracenecarboxylic acid.  
     
     
         5 . The method of  claim 4 , wherein said estrogenic carboxylic acid is selected from the group consisting of (+)-doisynolic acid, (−)-Z-bisdehydro-doisynolic acid, (+)-Z-bisdehydrodoisynolic acid, (±)-Z-bisdehydrodoisynolic acid, (−)-allenolic acid, (+)-allenolic acid, 1-(p-hydroxyphenyl)-6-ethyl-5-methylcyclohexene-4-carboxylic acid, 1-(p-hydroxyphenyl)-2-ethyl-3-methylcyclohexene-4-carboxylic acid, 1-(p-hydroxyphenyl)-2-ethyl-3,5,5-trimethylcyclohexene-4-carboxylic acid, 4-(p-hydroxyphenyl)-2,2,6,6-tetramethylcyclohexanecarboxylic acid, 1-ethyl-6-hydroxy-2-methyl-1,2,3,4-tetrahydroanthracene-2-carboxylic acid, 1-phenyl-2-ethyl-3-methylcyclohexene-4-carboxylic acid, and 1-phenyl-5,6-dimethylcyclohexene-4-carboxylic acid, or a pharmaceutically acceptable salt, ester, or anhydride thereof.  
     
     
         6 . The method of  claim 5 , wherein said estrogenic carboxylic acid is selected from the group consisting of (−)-Z-bisdehydrodoisynolic acid, (+)-Z-bisdehydrodoisynolic acid, and (±)-Z-bisdehydrodoisynolic acid.  
     
     
         7 . The method of  claim 3 , wherein said dosage is in the range of from about 0.1 μg/kg/day to about 100 mg/kg/day.  
     
     
         8 . A method for treating or preventing osteoporosis comprising administering an estrogenic carboxylic acid selected from the group consisting of a doisynolic acid, a phenylcyclohexenecarboxylic acid, a hydroxyphenylcyclohexenecarboxylic acid, a phenylcyclohexanecarboxylic acid, a hydroxyphenylcyclohexanecarboxylic acid, a hydroxytetrahydroanthracenecarboxylic acid, and a tetrahydroanthracenecarboxylic acid in a dosage effective to treat or prevent osteoporosis to a male or female patient suffering from, or disposed to, osteoporosis.  
     
     
         9 . The method of  claim 8  wherein said estrogenic carboxylic acid is selected from the group consisting of (+)-doisynolic acid, (−)-Z-bisdehydro-doisynolic acid, (+)-Z-bisdehydrodoisynolic acid, (±)-Z-bisdehydrodoisynolic acid, 1-(p-hydroxyphenyl)-6-ethyl-5-methylcyclohexene-4-carboxylic acid, 1-(p-hydroxyphenyl)-2-ethyl-3-methylcyclohexene-4-carboxylic acid, 1-(p-hydroxyphenyl)-2-ethyl-3,5,5-trimethylcyclohexene-4-carboxylic acid, 4-(p-hydroxyphenyl)-2,2,6,6-tetramethylcyclohexanecarboxylic acid, 1-ethyl-6-hydroxy-2-methyl-1,2,3,4-tetrahydroanthracene-2-carboxylic acid, 1-phenyl-2-ethyl-3-methylcyclohexene-4-carboxylic acid, and 1-phenyl-5,6-dimethylcyclohexene-4-carboxylic acid, or a pharmaceutically acceptable salt, ester, or anhydride thereof.  
     
     
         10 . The method of  claim 9 , wherein said estrogenic carboxylic acid is selected from the group consisting of (−)-Z-bisdehydrodoisynolic acid, (+)-Z-bisdehydrodoisynolic acid, and (±)-Z-bisdehydrodoisynolic acid.  
     
     
         11 . The method of  claim 8 , wherein said dosage is in the range of from about 0.1 μg/kg/day to about 100 mg/kg/day.