Preclinical and clinical properties of trimegestone: a potent and selective progestin.
Trimegestone (TMG) is a novel, 19-norpregnane progestin with potent and selective properties. In preclinical studies, TMG has been shown to provide high endometrial selectivity. Further, TMG has high affinity and selectivity for the progesterone receptor and lacks the agonist effects of other steroid hormones. In clinical studies, TMG has been shown to have high endometrial safety and an improved bleeding profile along with improved tolerability compared with other progestins. In addition, TMG also does not impede the beneficial effects of estrogen, especially on bone, and does not compromise quality of life. The preclinical findings of lack of mineralocorticoid activity of TMG were supported in clinical findings, with neutral effect on body weight. Similarly, the smaller effect of TMG on the GABA-ergic (gamma-aminobutyric acid) system in preclinical studies is consistent with the improvement of central nervous system-related effects on depressed mood and sleep quality in clinical studies. Low-dose estradiol/TMG regimens provide rapid relief from menopausal symptoms, reducing the number and severity of hot flushes as effectively as 2 mg 17beta-estradiol/1 mg norethisterone acetate. Therefore, it may be concluded that TMG provides a clinically proven option in hormone therapy for both clinicians and patients.
Sitruk-Ware
Regine
R
Rockefeller University and Population Council, New York 10021, USA. rsitrukware@popcbr.rockefeller.edu
Bossemeyer
Ronald
R
Bouchard
Phillipe
P
D000339:Affect / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003863:Depression / Q000523:psychology; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D011372:Progestins / Q000494:pharmacology / Q000627:therapeutic use; D011397:Promegestone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011980:Receptors, Progesterone / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D014592:Uterine Hemorrhage / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011372:Progestins; D011980:Receptors, Progesterone; C050319:trimegestone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D011397:Promegestone