Possible Interaction: Metformin and Progesterone

“The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin.”

“The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.”

“It was revealed that metformin treatment enhanced progesterone production by human granulosa KGN cells and rat primary granulosa cells induced by forskolin and FSH, respectively.”

“In the ovary, metformin directly decreased estradiol and progesterone production by human granulosa cells, and inhibition of progesterone production by metformin in rat granulosa cells caused an increase in phosphorylated AMPK (pAMPK).”

“Treatment with metformin (10mM), an activator of AMPK, increased AMPK phosphorylation (P<0.05) and reduced progesterone secretion by 50% (P<0.05) in the basal state and in response to IGF-1 or FSH in goat granulosa cells.”

“Previous studies have shown that metformin inhibits the first steps of steroidogenesis (Star, HSD3B) dose dependently reducing granulosa cells progesterone output [3].”

“The … of progesterone receptor-positive mammary carcinomas in … who were treated with metformin , irrespective of whether it was combined with sulfonylurea preparations, was significantly higher than in the sulfonylurea only group (… = 0.043) and in the combined group of patients treated with either sulfonylurea or insulin (P = 0.041).”

“Our data suggest that metformin treatment attenuates progesterone secretion via AMPK-independent pathways in granulosa cells of prehierarchical and preovulatory follicles of broiler breeder hens.”

“The expression of genes related to steroidogenesis such as FSHR, STAR, CYP11A1, HSD3B, and progesterone secretion was significantly decreased in response to metformin treatment in a dose-dependent manner.”

“In vitro studies show that MET decreases gonadotropin-releasing hormone and gonadotropins release in rat neurons, and decreases progesterone and estradiol in rat granulosa cells and androstenedione synthesis in human theca cells.”

“In granulosa cells from small follicles, metformin (10 mM) reduced production of both progesterone and estradiol and decreased the abundance of HSD3B, CYP11A1, and STAR proteins in presence or absence of FSH (10−8 M) and IGF1 (10−8 M).”

“ Metformin (10 mM) treatment for 48 h reduced progesterone and estradiol (E2) production in both basal conditions and under FSH stimulation.”

“Our results therefore strongly suggest that metformin reduces progesterone production via a PRKAA-dependent mechanism, whereas PRKAA activation is not essential for the decrease in E2 production and cell growth induced by metformin in rat granulosa cells.”