Hypothalamic amenorrhoea is the cessation of menstruation for six months or more, or for more than three menstrual cycles (when the cycle is longer than usual) in women who previously had regular periods. Common causes are anorexia, excessive exercise and stress. The hypothalamus stops producing GnRH, which leads to a reduction in the pulsatile release of FSH and LH by the pituitary, and ultimately to reduced levels of the ovarian hormones oestrogen and progesterone. Ovulation and menstruation stop, and infertility is the result. This condition is sometimes also called functional hypothalamic amenorrhea, and affects about 5 per cent of women in their reproductive years.
Hypothalamic amenorrhoea can have significant consequences. Low oestrogen is associated with osteoporosis when left untreated for long enough, and other symptoms of low oestrogen can become troublesome. Anorexia nervosa is a significant cause of morbidity, and mortality can be as high as 15 per cent. Women who over-exercise and have amenorrhoea often believe that their bone density is protected by the amount of exercise they do, but this is often not the case. The effects of over-exercising, eating disorders, poor eating habits and stress on the menstrual cycle have been discussed in detail in Chapter 10 ‘The usual suspects’. Hypothalamic amenorrhoea is the most serious gynaecological manifestation of these behaviours.
The most important causes of hypothalamic amenorrhoea are stress, poor dietary habits and excessive exercise. Some of the research into hypothalamic amenorrhoea has tried to identify whether there are different types of hypothalamic dysfunction represented by different patterns of LH pulsatile release. However, when hormone levels from women with hypothalamic amenorrhoea were examined, it was found that LH secretion patterns varied between women and within the same woman, indicating that most women with this condition do not have a static defect in GnRH secretion, but rather have changing patterns of GnRH secretion that vary over time irrespective of the actual cause of the hypothalamic amenorrhoea.
Recent investigations have shown that cortisol levels are higher in stressed women with hypothalamic amenorrhoea that in non-stressed women with the same condition. Stress has a number of diverse effects on the hypothalamic-pituitary-ovarian axis, as well as on the hypothalamic-pituitary-adrenal axis. These are discussed in ‘The usual suspects’. Researchers found that women with hypothalamic amenorrhoea had similar psychological profiles, including a tendency towards perfectionism and poor nutritional or lifestyle choices. Many were likely to attempt an unrealistic number of tasks in one day.
The endocrine system seems to function best when an individual adopts a lifestyle philosophy of moderation in all things. For women with stress-induced amenorrhoea, participation in psychotherapy sessions or cognitive behavioural therapy may be useful. Gentle exercise, yoga, meditation and relaxation techniques will need to be incorporated into the treatment regime for any satisfactory or long-lasting results. The association between inappropriate eating, stress and hypothalamic amenorrhoea suggests that dietary counselling may also be necessary.
Although only about 5 per cent of women develop functional amenorrhoea, between 25-60 per cent of this group stops menstruating because of exercise-induced amenorrhoea. Generally, these women participate in endurance sports such as distance running, but other activities where it is customary to closely monitor body weight, such as gymnastics, also contribute significantly to this group. The major concern regarding exercise-induced amenorrhoea is the reduction of bone density that can lead to serious consequences related to oestrogen deficiency. Exercise is discussed in more detail in ‘The usual suspects’. Suppression of hypothalamic pulsatile release of GnRH is the cause of the amenorrhoea. Initially, it was believed that an abnormal BMI was the primary trigger for the inadequate GnRH release, but it is now believed that when dietary energy intake does not meet energy expenditure, and causes a drop in metabolic rate, adaptive changes occur in reproductive function which lead to a decrease in pulsatile release of GnRH. It may also be that leptin has a role in this condition. Leptin is a hormone secreted by fat cells and optimum levels are required for the initiation and maintenance of menstrual cycle regularity. Hypothalamic amenorrhoea is more likely to occur when low leptin levels are associated with low kilojoule intake and a BMI below 20 than when BMI is low but kilojoule intake is adequate.
Poor eating habits
The effects of poor eating patterns on the menstrual cycle have already been discussed in ‘The usual suspects’. Hypothalamic amenorrhoea seems to occur when nutritional deficiencies cause low body weight and inadequate body fat, leading to low oestrogen levels and increased risk of osteoporosis. This picture is exacerbated when kilojoule intake does not meet energy expenditure requirements. It has become apparent that the type of kilojoules is an important consideration in the prevention of hypothalamic amenorrhoea. When dietary energy is derived from carbohydrate foods instead of from adequate fat or protein intake, amenorrhoea is more likely to occur. For example, restricted eating patterns in normal weight, non-athletic women, such as very low fat intake, high fibre intake and a kilojoule intake that did not meet the energy expenditure of daily aerobic activity, were shown to increase the risk of amenorrhoea. Targeting the cause of the low oestrogen, in this case the dietary problems, is a more appropriate way of dealing with this issue than using replacement hormones.
Leptin levels are also implicated. When nutrition restrictions are severe, leptin levels fall irrespective of the BMI, body fat ratio or body weight. Menstruation does not occur when leptin levels are low, perhaps because the hypothalamic response to this apparent state of starvation is to reduce ovulation and menstruation to preserve the health of the woman and prevent pregnancy which would entail some risk to both mother and unborn child.
While low levels of gonadotropins and oestrogen are suggestive, hypothalamic amenorrhoea is a diagnosis of exclusion. Hyperprolactinaemia, PCOS, hypothyroidism and hypothalamic amenorrhoea are all likely diagnoses when a woman develops secondary amenorrhoea. Pregnancy should also be eliminated as the cause of absent menstruation. Clinical evidence of androgen excess, such as hirsutism and acne, or amenorrhoea secondary to weight gain, point to a possible diagnosis of PCOS. Blood levels of prolactin and TSH are usually evaluated in conjunction with oestrogen, LH and FSH to rule out hyperprolactinaemia and hypothyroidism. Sometimes a progestogen challenge might be suggested to determine whether uterine function is normal, but this is only useful when oestrogen levels are adequate. When oestrogen is low a withdrawal bleed does not occur because the endometrial proliferation is absent. Premature ovarian failure, a less common cause of amenorrhoea, presents with elevated FSH and LH, but low levels of oestrogen.
Hypothalamic amenorrhoea should also be suspected in athletes or other women undertaking endurance sports, when abnormal eating patterns are revealed, or when a woman describes an episode of recent stress. Post-Pill amenorrhoea is a type of hypothalamic amenorrhoea, but is very rare. Sometimes hypothalamic amenorrhoea occurs for unknown reasons.
The medical approach
Women with hypothalamic amenorrhoea should be started on treatment as soon as possible. It is preferable that this involves some attention to the underlying cause/s not just replacement hormone therapy. Hormone replacement and oral contraceptives can be used to minimise the loss of bone density caused by a prolonged lack of oestrogen, until the causes are identified and appropriate treatment is used to rectify these. However, unless the causes for hormonal loss are addressed, oestrogen replacement has not been shown to be very effective.
The natural therapists’s approach
The treatment of hypothalamic amenorrhoea will need to be partially directed towards the cause, such as consuming more kilojoules in the form of protein and fats, exercising less or addressing the adverse effects of stress (see ‘The usual suspects’).
Other herbal treatment aims to reinstate normal hypothalamic-pituitary-ovarian feedback control with herbs such as Vitex agnus-castus and Paeonia-lactiflora. Pulsed treatment with steroidal saponin-containing herbs may also be useful. The method for prescribing these herbs is outlined in ‘Improving ovulation and fertility’ in the PCOS section.
Selections from the book: “ Women, hormones and the menstrual cycle. Herbal and medical solutions from adolescence to menopause”. Edited by Ruth Trickey, 2004.