Abstract
BACKGROUND: Follicle Stimulating Hormone (FSH) is central to follicular growth during the menstrual cycle. It is secreted in multiple isoforms that differ in glycosylation, bioactivity, and half-life. Acidic isoforms dominate early in the follicular phase, while less acidic forms rise closer to ovulation caused by increasing oestradiol. Though well studied in vitro, the distinct physiological roles of these isoforms in vivo are not fully understood. METHODS: We conducted a narrative review of published literature focusing on FSH isoforms composition, glycosylation patterns, and their functional roles during the human menstrual cycle, with emphasis on isoform-specific actions in follicular development. MAIN FINDINGS: It is proposed that acidic FSH isoforms primarily support early follicular grow by stimulating inhibin-B production, which enhance androgen synthesis in synergy with LH. These androgens, in turn, increase FSH receptor expression in granulosa cells, promoting follicle sensitivity. In the later follicular phase, less acidic isoforms support final follicular maturation by upregulating aromatase and LH receptor expression in granulosa cells, facilitating the shift from androgen to oestrogen production. CONCLUSION: The sequential dominance of FSH isoforms appears to guide distinct stages of follicular development. Understanding this temporal regulation may lead to improvements in ovarian stimulation strategies and enhance outcomes in assisted reproduction.