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Introduction to two new tests: AMH and FSH

31 januari 2020

The anti-Müller hormone (AMH) and follicle stimulating hormone (FSH) are two hormones that are closely involved in the growth and development of egg cells. The stock of eggs is stored in the ovary. They are safely packed in so-called follicles. A continuous number of follicles are stimulated to grow so that the egg cell can prepare itself for fertilization. Unhealthy diet and lifestyle can influence the development of these follicles and the degree of fertility. Measurement of AMH and FSH provides insight into the quantity and quality of the follicles.

Function in the body

The development of the gonads is the same during the first six weeks, so there is no external difference between a male and a female embryo. The internal and external genitals are still the same. In the lower abdomen are the precursor of the primordial gonads and two double-sided tubes, the Müller tube and the Wolff tube. The primeval gonads grow into testes or ovaries. The Müller tube only grows with the female embryo and the Wolff tube only with the male embryo. With male embyos very large amounts of Anti-Muller's Hormone (AMH) are produced in week 6 so that the Müller tube does not develop further. Even after birth the AMH concentration in serum in boys is still very high. 

AMH is produced in women of childbearing age by small growing egg vesicles (the follicles) in the ovary. In a certain growth stage of the follicle a small fluid-filled cavity (antrum) forms, we speak of antral follicles. If these follicles have a size of 2-7 mm then the number of granulosa cells in the follicles increases and they procud a lot of AMH. Of all present follicles with a size of 8-12 mm, one is chosen to grow into a large preovulatory follicle, the rest is broken down. This process of continued growth and selection of the dominant follicle is determined by the presence of sufficient FSH, a hormone produced in the pituitary gland. But at the same time, the antral follicles also produce estradiol, which inhibits FSH release in the pituitary gland. The follicle that has absorbed the most FSH in a short period of time and has grown the fastest has won. The oocyte in this follicle matures further and is released when the follicle bursts open (ovulation or ovulation). The latter process of selection and maturation takes 14 days (first part of the menstrual cycle). The moment of ovulation is determined by a strong increase in other pituitary hormone, namely LH. 

A few resting (primordial) follicles are continuously stimulated to grow. If sufficient (or too much) AMH is present, this stimulus to growth is slowed down by AMH (negative feedback) and stimulated again when the AMH level drops. The more antral follicles present, the higher the AMH content. There is a very good correlation between the number of growing follicles in the ovaries and the AMH level in the blood. There should be a minimum number of growing follicles of about 15 for a good chance of pregnancy corresponding with an AMH value of at least 0.7 µg/l.  AMH is highest in young women between 13 and 30 years of age. With increasing age the AMH level gradually decreases to a post-menopausal value of zero.

It is clear that a good ovulation is highly dependent on the dynamics of estradiol, LH, FSH, and AMH. It appears that lifestyle and nutrition can contribute to an optimal ovulation cycle. 

Values in the blood

Prediction of (early) menopause

On average, a woman enters menopause at the age of 50, with a spread of 10 years. We speak of premature reproductive failure (POF) when menopause occurs before the age of 40. A very low AMH (< 0.07 µg/l) means that no or very little growing follicles are present and correspondingly with menopause. The menopause can be definitively diagnosed if there has not been another one for a year after the last menstruation; it can therefore only be diagnosed retrospectively. The AMH and FSH tests can give a clue in advance as to whether irregular or no cycle announces the beginning of menopause. The combination of decreased AMH and increased FSH is a fairly strong predictor. 

Up to the age of 30, AMH is the highest in blood. After that it gradually decreases, for most women about 0.15 µg/l per year to 45 years of age, and then decreases slightly less rapidly. Calculation models have been made with which we are able to estimate when menopause will occur. For women under 30 years of age and high/normal AMH values, this prediction is too inaccurate; the accuracy increases with increasing age and lower AMH values. For example, if a woman has an AMH value of 1.5 µg/l at the age of 25, it is not wise to wait another 10 years to become pregnant. There is a high chance that AMH will then fall below 0.7 µg/l, which is a limit value that significantly reduces the chance of spontaneous pregnancy. 

The combination of AMH and FSH are therefore very useful to get an indication of the follicle stock and to estimate when menopause may occur. Both tests are also useful when there is doubt about postponing a pregnancy in order to be ahead of premature ovary failure. It is important to realize that an optimal AMH value is a prerequisite, but does not guarantee pregnancy. Fertility depends on much more than just a good supply of growing follicles. AMH can therefore not be used as a measure of fertility and for a probability calculation of pregnancy. Women under treatment at a fertility clinic have an average AMH value comparable to that of fertile women of the same age. However, the average age is relatively high.

AMH and FSH in Polycystic Ovarian Syndrome (PCOS)

For AMH, the statement 'the more the better' certainly does not apply. There are situations in which there are many antral follicles, but the ripening of the egg and the growth of the follicles is not going well. The follicles do grow larger, but do not mature properly. Therefore, cystic follicles can develop. If the size and number of these follicles increase considerably and there are specific symptoms and syptoms, we speak of polycystic ovarian syndrome (PCOS). This is accompanied by increased AMH values, but less chance of pregnancy. The chance of PCOS increases when the AMH value is higher than the age limit. There are also studies that indicate that an AMH value above 5 ug/l already indicates an increased risk of PCOS (or in its early stages). AMH may not be used as a diagnostium for PCOS (the so-called 'Rotterdam' criteria have been drawn up for this purpose), but it does give a good indication.

FSH is strongly cycle dependent and can only be properly interpreted if blood sampling takes place on day 2-5 after the first day of menstruation (start of a new cycle), preferably on day 3. In women who have no or very irregular menstruation, simultaneous AMH and FSH determination is necessary for proper interpretation. On day 3 of the cycle the oestradiol level in the blood is stably low, leading to a basal FSH value between 3 and 10 U/l.

Functional hypothalamic amenorrhea

Another reason for menstruation failure longer than 6 months (amenorrhea) can be a negative energy balance, whether or not combined with active sports practice and/or acute psychological stress factor. In this case the hypothalamus is suppressed in such a way that GnRH excretion no longer takes place or is too weak. This is useful for the body to maintain energy for vital functions. Hence the term functional hypothalamus ammenoroe. Both FSH and LH release are lower than in women with normal cycles of similar age. However, the AMH values in serum are not lowered. They are normal and in some cases even increased. When AMH is increased in these women it is very similar to PCOS (but with a lower FSH value) and often with an increased number of follicles. There is a slightly higher risk that they will develop PCOS later on. When the stress triggers (negative energy balance, excessive exertion, psychological stress) are reduced, the menstrual cycle normalizes again.


The AMH content in serum/plasma has a fairly large intraindividual distribution, depending on the number of large end follicles (see above). The reference values are always reported by us depending on age and gender (this does not apply to all laboratories). For a 19 year old woman this is 0.8-8.0 µg/l and for a 40 year old woman it is 0.1 - 4.0 µg/l. For all ages we use an optimal AMH value of 0.7 - 5.0 µg/l. If AMH falls below 0.7 µg/l, fertility decreases and if AMH has fallen below 0.07 µg/l, we speak of biological menopause.

We speak of premature ovarian failure in menopause before the age of 40. This can already be predicted 10 years earlier by finding AMH levels that are too low for their age, taking into account an average decrease of 0.15 µg/l per year.

In women with oligo- or ammenorrhoea and AMH values higher than 5.0 µg/l (in young women higher than 8.0 µg/l) and the FSH low/normal (3 - 8 U/l) the chance of PCOS increases (especially if it also exceeds the age-dependent reference limit) and the chance of pregnancy decreases.

In women with ammenorrhoea and age normal AMH values, but with reduced FSH values (< 3 U/l) the chance of functional hypothalamic ammenorrhoea caused by a prolonged negative energy balance, whether or not combined with excessive exercise and/or psychological stress, is high.