Contents
Introduction
The menstrual cycle is on average, 28 days long. It can be between 20-45 days. It varies from person to person, and month to month.
A few quick facts:
- Both oestrogen and progesterone are produced from cholesterol
- LH and FSH are known as the gonadotropins
- GnRH is released in a pulsatile fashion. These pulses last 5-25 minutes, and occur every 1-2 hours. They result in the pulsatile release of LH and FSH. When GnRH is produced continuously, its ability to cause the release of LH and FSH is lost. GnRH release is:
- Low in childhood, and activated during puberty
- Controlled by feedback loops of oestrogen (stimulated GnRH) and progesterone (inhibits GnRH)
- Suppressed in pregnancy by prolactin
- Disrupted in Polycystic ovary syndrome
- Affected by hypothalamic-pituitary disease – e.g. space occupying lesion, trauma.
Phases
The menstrual cycle can be divided into the follicular phase and the luteal phase, with both being 14 days long.
Follicular phase
During this phase, ovarian follicles are stimulated to grow, and one of the follicles will emerge as dominant, and eventually be released by the ovum. The point of release is the point at which the luteal phase begins.
- The normal ovary contains many primary follicles – these have the potential to become ovum under the correct stimulation. They contain a large, central oocyte, surrounded by several small follicular cells.
- During the follicular phase, under the stimulation of FSH, up to 20 primary follicles are stimulated to grow. They become secondary follicles. They are essentially in a race to become the next ovum. As they grow, the number of follicular cells increases rapidly, and the follicular cells differentiate to become Granulosa Cells.
- By day five of the cycle, one of the follicles emerges as the dominant follicle, aka the Graafian , or Tertiary follicle. During days 6-14 this follicle grows rapidly in response to FSH. During this time it will release Oestrogen, which will act as a positive feedback loop, by stimulating the production of more GnRH, as well as accounting for secondary sex characteristics, and having important effects on muscle and bone metabolism.
- Now stimulated by a rise in LH, this is stimulated to complete its suspended state of meiosis I, and in doing so the oocyte splits in two, releasing one large cell, and one small polar body. This continues meiosis as far as metaphase II, which is not completed until fertilisation.
- Then, the oocyte is released from the ovum, and into the fallopian tube. This is the start of the luteal phase
Luteal Phase
- The empty follicle remains in the ovary, as becomes the corpus luteum. Under stimulation of LH this will slowly secrete progesterone, in increasing amounts for 7 days, after which time is begins to degrade, and progesterone output falls.
- Progesterone is responsible for the build up and maintenance of the endometrium. In the absence of progesterone, the lining will die and slough off (menses).
- In the absence of fertilisation – The corpus luteum will produce progesterone and oestrogen for 14 days, as it slowly degrades.
- The corpus luteum never completely disappears. It remains in the ovary as the corupus albicans, which is essentially just a mass of fibrous scar tissue. In older women, the build up of these bodies can cause misshaped ovaries.
- In the presence of fertilisation – the implanted embryo will produce hCG (Human chorionic gonadotropin). This stimulates the corpus luteum to continue producing progesterone, to maintain the endometrium. At this stage, the corpus luteum is called the corpus luteum graviditatis
- Eventually, the placenta will take over the production of progesterone, once it becomes large enough.
- In menses- between 35-80ml of blood is lost
- It typically lasts 3-5 days
- The highest rate of fertility (the time when sex is most likely to result in pregnancy) is from 5 days before ovulation to 2 days after ovulation.
- In a normal 28 day cycle, with a 14 day luteal phase, this is roughly 5-12 days after the end of menses.
- Note the two peaks of Oestrogen:
- The first is the production of oestrogen by the tertiary follicle, and its main role is to prepare the endometrium for implantation
- The second is the production of oestrogen by the corpus luteum.
- Oestrogen inhibits the anterior pituitary release of FSH and LH – and this effect is exaggerated in the presence of progesterone (i.e. more exaggerated in the second half of the cycle).
- Inhibin also has a large inhibitory effect, particularly on FSH release.
- Endometrium – the growth of the endometrium and swelling of individuals cells occurs to provide enough nutrients to a developing fetus. In the cells there are high levels of lipids, proteins and glycogen as well as other nutrients that an embryo will need.
- After implantation, the decidua (the endometrial cells) will provide all nutrition for the first 16 days, and will continue to supply some nutrition until about the 16th week, when the placenta is developed enough to take on the role fully.
Explanation of the cycle
- After Ovulation – days 15-28 – the corpus luteum is secreting lots of progesterone, oestrogen and inhibin. This keeps levels of FSH and LH low. As corpus luteum output falls, FSH and LH levels rise, reducing inhibition of the anterior pituitary; leading to the start of the next cycle, and the activation of several primary follicles to begin development.
- Days 1-11 – FSH and LH production gradually fall, as they stimulate the follicles to produce oestrogen, which inhibits FSH and LH production.
- Days 12-14 – The excessively high level of oestrogen stimulate the production of very high levels of FSH and LH, as the negative feedback loops is reversed. This causes ovulation, and results in the creation of the corpus luteum.
- Sometimes, the LH surge is not great enough to cause ovulation – these cycles are known as ‘anovulatory’. These typically occur during puberty, as the reproductive system matures, and also occur just before the menopause. In these cases, no ovum is released, and although the cycle will continue, it is shortened, and there is no production of the corpus luteum, and no production of oestrogen and progesterone in the second phase of the cycle.
More about the hormones
FSH – follicle stimulating hormone
FSH is produced by the anterior pituitary gland. Its release is affected by GnRH pulses.
It has several effects in both males and females including development, growth and puberty. In men in is also related to the production of sperm, and in women, in combination with LH, it helps to regulate the menstrual cycle and cause ovulation. In particular it helps to select the most mature follicle to advance to ovulation.
In women, the level of FSH varies depending on the timing of the cycle. In men, FSH levels remain steady after puberty.
- Testing levels of FSH is occasionally used to diagnose menopause
- In most cases – menopause is a clinical diagnosis (i.e. diagnosed without the use of tests)
- However ins one cases – typically those where early menopause is suspected (e.g. less Thant he age of 40 with no periods for >1 year) then FSH levels may be tested
- FSH levels that are consistently raised can be used to confirm the diagnosis of early menopause. Typically this requires two tests that are 4-6 weeks apart
References
- Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
- Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
- Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy