The development of oogonia in women starts as a fetus, with an absolute number of immature follicles. At birth, all of a woman's immature follicles lie dormant in her ovaries. At puberty, maturation of the sexual organs and development of secondary sexual characteristics occurs. Adrenarche (the growth of hair in the axillae and pubic area), thelarche (the growing of the long bones), and menarche (onset of menstrual bleeding) occur as part of this process. The average age of menarche is 13 years, although any age between 8 and 18 can be normal. It is associated with Body Mass Index (BMI) and nutritional status. Rising hormone levels lead to the maturation of several ovarian follicles per month, one of which is usually released. Menstruation is the cyclical loss of blood per vaginum, a result of endometrial shedding when implantation of an ovum fails to occur. Normal loss is approximately 25ml/day for 4-5 days. Menstruation occurs until menopause, unless interrupted by pregnancy. From birth, the number of follicles declines steadily, but from around the age of 37 levels decline much more rapidly. This is the basis of the so-called ‘ticking of the biological clock’.
The menstrual cycle describes the monthly physiological changes that prepare women for pregnancy and end in endometrial shedding and bleeding should this not occur. The average cycle lasts 28 days.
This article will cover:
- Hormonal control of the menstrual cycle
- Ovarian changes
- Endometrial changes.
Three sets of hormones control the menstrual cycle, known as the hypothalamic-pituitary-ovarian axis:
- Hypothalamic hormones: Gonadotrophin-Releasing Hormone (GnRH)
- Anterior pituitary hormones: Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
- Ovarian hormones: oestrogen and progesterone.
Changes in the secretion of these hormones throughout the cycle allow:
- Maturation and release of gametes from the ovary
- Development of a uterine environment able to support a pregnancy.
The ovarian changes are easiest to understand if divided into four stages:
- Follicular development
- Luteal phase
This is the phase leading up to ovulation; it typically comprises the first 14 days of a 28-day cycle, where day 1 is the first day of menstrual bleeding.
- In very early follicular development (recruitment), primordial ovarian follicles develop into antral follicles, capable of complete maturation. Each month, hundreds of primordial follicles grow, but most will undergo atresia.
- In early follicular development (selection), follicles undergo morphological changes under the influence of FSH. The granulosa cells proliferate and aromatase activity converts testosterone produced by theca cells into oestrogens. Oestrogen levels increase.
- In late follicular development, FSH secretion rapidly diminishes because of negative feedback on the hypothalamic-pituitary-ovarian axis by the rising oestrogen levels. By days 5-7, only one dominant follicle can continue to respond, the one with the largest number of granulosa cells (which contain FSH receptors). This is also known as the Graafian (dominant) follicle. FSH also stimulates the synthesis of LH receptors on granulosa cells, thereby initiating LH responsiveness. Continued levels of circulating oestrogen and another hormone, inhibin, suppress FSH secretion to prevent new follicular development.
- In the pre-ovulatory phase, LH is the chief hormone. Previous FSH stimulation of the dominant follicle primes it with LH receptors. An LH surge is triggered by rising levels of oestrogen in the dominant follicle. As a result of the surge, oestrogen levels decline and the granulosa cells switch to progesterone production. Nuclear maturation involves the chromosomes progressing through the remainder of the 1st meiotic division, and arresting in metaphase of the 2nd meiotic division.
- In ovulation, between days 13 and 15, the follicle ruptures with escape of the oocyte. Tubal and ovarian motility ensure that tubal fimbriae sweep over the ovarian surface to take in the freshly ovulated egg. With rupture of the follicle there may be pain - mittelschmerz - as the follicle fills with blood beforehand.
- In the luteal phase, progesterone is the main hormone. After ovulation, the follicle gives rise to a new structure, the corpus luteum, which synthesises progesterone and oestrogen. The corpus luteum has 2 functions: 1) provide hormonal stimulus for target organs, and 2) regulate the menstrual cycle. Progesterone depletes local oestrogen receptors, and acts synergistically with oestrogen to inhibit gonadotrophin secretion by negative feedback. Both hormones cause uterine endometrial proliferation in preparation for implantation. The corpus luteum declines rapidly 9-11 days post-ovulation if fertilisation does not occur. Progesterone secretion and inhibin levels fall so the endometrium is shed in menstruation. This allows increased GnRH and FSH secretion in preparation for the next cycle. If fertilisation does occur, the corpus luteum is maintained by the trophoblast, which secretes Chorionic Gonadotrophin hormone (hCG) – a hormone analogous to LH.
- Day 1 of menstruation signifies the start of a new menstrual cycle. A new wave of follicles is recruited, which will then progress towards maturation.
Endometrial changes can be divided into three phases:
- Proliferative phase
- Secretory phase
- Menstrual phase
In the proliferative phase, the uterine lining and uterine glands become thicker as epithelial and stromal cells undergo mitosis. The endometrial lining builds up to approximately 3.5-5.0mm in height. This phase is under oestrogen control. Oestrogen causes upregulation of oestrogen receptors (thus enhancing its own effect) and progesterone receptors, to prime the endometrium and enable it to respond to progesterone in the luteal phase.
In the secretory phase, after ovulation has occurred, the glands become convoluted and dilated with secretions. The spiral arteries that supply the glands become more prominent, and increasingly corkscrew in appearance. This phase is stimulated primarily by progesterone secreted by the corpus luteum.
In the menstrual phase, the endometrium sloughs and bleeding occurs as the hormonal support is lost: this is menstruation. Flow is limited by endometrial repair - resumption of oestrogen secretion by the new developing follicle induces healing and new tissue growth. The blood supply is maintained by the straight arteries of the basal layer.
Kumar P, Clark M. Kumar and Clark Clinical Medicine. 6th ed. Saunders Ltd.
McKay Hart D, Norman J. Gynaecology Illustrated. 5th ed. Churchill Livingstone.
Elder MG. Obstetrics and Gynaecology: Clinical and Basic Science Aspects. Imperial College Press.
Heffner LJ, Schust DJ. The Reproductive System at a Glance. 3rd ed. Wiley-Blackwell.