Methods and compositions for treating polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is characterized by elevated levels of androgens, cysts in the ovaries, and irregular periods. Women with PCOS present with additional symptoms, including hirsutism, alopecia, acne, infertility, weight gain, fatigue, depression and mood changes. The present disclosure provides new compounds, salts, compositions and uses thereof in the treatment of PCOS due to elevated adrenal androgens. Further, the present disclosure provides methods for treating PCOS due to elevated adrenal androgens.
1. A method of treating polycystic ovary syndrome with functional adrenal hyperandrogenism (PCOS-FAH) in a subject in need thereof, comprising administering a CRF 1 antagonist or pharmaceutically acceptable salt thereof;
wherein said CRF 1 antagonist is a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 are independently ethyl or n-propyl;
R 3 is hydrogen, F, Cl, Br, methyl, trifluoromethyl, or methoxy;
R 4 is hydrogen, Br, —NR a R b , methoxymethyl, n-butyl, acetamido, pyridin-4-yl,
morpholin-4-yl,
R a and R b are independently hydrogen, C 1 -C 3 alkyl, —CH 2 CH 2 NH 2 , —CH 2 CH 2 NHC(O)OC(CH 3 ) 3 , or —CH 2 CH 2 NHCH 2 CH 2 CH 3 .
2. The method of claim 1 , wherein the compound of Formula (I) is
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 5 mg to about 400 mg total daily dose to the subject.
4. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 300 mg total daily dose to the subject.
5. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 200 mg total daily dose to the subject.
6. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 150 mg total daily dose to the subject.
7. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 100 mg total daily dose to the subject.
8. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 75 mg total daily dose to the subject.
9. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 50 mg total daily dose to the subject.
10. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 25 mg total daily dose to the subject.
11. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is administered in a dose of about 10 mg total daily dose to the subject.
12. The method of claim 1 , wherein an adrenocorticotropic hormone (ACTH) level is reduced by at least 10% from baseline.
13. The method of claim 1 , wherein a dehydroepiandrosterone sulfate (DHEAS) level is reduced by at least 10% from baseline.
14. The method of claim 1 , wherein androstenedione (A4) level is reduced by at least 10% from baseline.
15. The method of claim 1 , wherein 1β-hydroxyandrostenedione (11OHA4) level is reduced by at least 10% from baseline.
16. The method of claim 1 , wherein 11β-hydroxytestosterone (11OHT) level is reduced by at least 10% from baseline.
17. The method of claim 14 , wherein said reduced A4 level from baseline is maintained for at least 24 hours.
18. The method of claim 2 , wherein the compound of Formula (I) is administered at a dose between about 1 mg/day and about 200 mg/day.
19. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is in the form of a pharmaceutical composition, wherein the pharmaceutical composition is in the form of microparticles.
20. The method of claim 1 , wherein the CRF 1 antagonist or pharmaceutically acceptable salt thereof is in the form of a pharmaceutical composition, wherein the pharmaceutical composition is in the form of a capsule or a tablet.
21. The method of claim 1 , wherein the subject is a pediatric patient or an adult patient.