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The follicular phase (or proliferative phase) is the phase of the estrous cycle, (or, in humans and great apes, the menstrual cycle) during which follicles in the ovary mature. It ends with ovulation. The main hormone controlling this stage is estradiol.^[1]

Contents 1 Hormonal events 1.1 Follicle-stimulating hormone 1.2 Luteinizing hormone 2 Follicular waves 3 References

Follicle-stimulating hormone (FSH) is secreted by the anterior pituitary gland. FSH secretion is highest and most important during the first week of the follicular stage of the menstrual cycle.^[2] The rise in FSH levels recruits five to seven tertiary-stage ovarian follicles (this stage follicle is also known as a Graffian follicle or antral follicle) for entry into the menstrual cycle. These follicles, that have been growing for the better part of a year in a process known as folliculogenesis, compete with each other for dominance. FSH is essential for follicle growth at this stage of the cycle.

FSH also induces estrogen secretion in these follicles by activating aromatase and p450 enzymes.^[2] Estrogens initiate the formation of a new layer of endometrium in the uterus, histologically identified as the proliferative endometrium. Estrogens also stimulate crypts in the cervix to produce fertile cervical mucus.^[3] This mucus reduces the acidity of the vagina, creating a more hospitable environment for sperm.^[4] It also has a characteristic texture that helps guide sperm through the cervix^[5] and to the fallopian tubes, where they wait for ovulation.^[6] This mucus may be recognized by women practicing fertility awareness.

FSH causes negative feedback on gonadotropin-releasing hormone (GnRH) secretion.

FSH also induces the proliferation of granulosa cells and the expression of luteinizing hormone (LH) receptors on these granulosa cells.^[2] Estrogen levels are highest right before the LH surge begins. The short-term drop in steroid hormones between the beginning of the LH surge and the event of ovulation may cause mid-cycle spotting or bleeding.^[7]

LH is secreted by the anterior pituitary gland and is required for growth of preovulatory follicles.^[2] LH also stimulates the growing follicles to secrete increasing amounts of estradiol, an estrogen that acts to inhibit pituitary secretion of FSH. With diminished FSH supply comes a slowing in growth that eventually leads to follicle death, known as atresia. The largest follicle, called the dominant follicle, secretes inhibin that serves as a finishing blow to less competent follicles by further suppressing FSH.

LH induces androgen synthesis by thecal cells, stimulates proliferation, differentiation, and secretion of follicular thecal cells and increases LH receptor expression on granulosa cells. The preovulatory LH surge starts the first meiotic division in oocytes and initiates luteinization of thecal and granulosa cells.^[2] Ovulation normally occurs between 12 and 36 hours after the beginning of the LH surge.

The time from recruitment of tertiary stage follicles to ovulation is normally about a week, comprising days 5-14 of an idealized 28-day menstrual cycle. However, it is common for the follicular phase to last much longer, as sometimes no dominant follicle is selected. In this case, normally more tertiary stage follicles are recruited and the process begins again. One study of women with regular menstrual cycles found that none of them ovulated after the first wave of follicle development: 68% of cycles showed ovulation after the second wave, while 32% of cycles showed ovulation after the third wave.^[8] Fertility awareness sources may refer to multiple waves of follicular development as a split peak because of the characteristic pattern of cervical mucus changes that is sometimes observed.^[9]