"Contrary to what had previously been believed", she said, "we found that multiple small stressors that seemingly would have minimal impact on reproductive competence can play a major role in causing anovulation. Up till now it was thought that failure to ovulate was usually caused by the energy deficits induced by excessive exercise and/or undernutrition, but we asked why women undertake such behaviours. Often dieting and exercise are a way of coping with psychosocial stress, and our previous work had shown that such stress is often increased in women who do not ovulate."
Professor Berga and her team set out to study the causes of functional hypothalamic amenorrhea (FHA) in women of normal weight who had not had a menstrual period for more than six months. FHA is caused by a prolonged reduction in gonadotropin-releasing hormone (GnRH), which signals the release into the bloodstream of hormones that simulate ovulation.
Analysis of the cerebrospinal fluid in women with FHA, as opposed to women who were ovulating normally, showed increased levels of cortisol, a hormone related to stress. Chronic elevation of cortisol levels heightens the risk for other health burdens, such as depression or osteoporosis, but chronic cortisol increases can often be reversed with behavioural therapy
In a pilot study, Professor Berga's team randomised 16 women with FHA into two groups. One group received cognitive behaviour therapy (CBT) for 20 weeks; members of the other group were observed. "A staggering 80% of the women who received CBT started to ovulate again, as opposed to only 25% of those randomised to observation", said Professor Berga. "Neither group gained weight nor showed significant changes in their levels of leptin, a hormone involved in regulating body weight and metabolism. This study underlines the important contribution that lifestyle factors play in determining overall health and reproductive health in particular. To reverse stress-induced ovulation, it is not enough simply to address metabolic sources of stress."
Professor Berga told the conference that the recovery of the stress and ovarian axes appears to occur independently of major metabolic changes such as an increase in leptin or thyroxine (a hormone that affects how cells use energetic compounds). Since CBT caused a drop in cortisol and a rise in TSH, it may be that the hypothalamic-pituitary-thyroid axis, involved in the regulation of metabolism, recovers, but only later.
The current practice in the treatment of anovulatory women is to offer hormonal treatments such as oral contraceptives, if immediate fertility is not desired, or ovulation induction if it is. "Aside from cost, these approaches mask ongoing endocrine disturbance", said Professor Berga. "Since these disturbances pose a risk to overall health, it is important to use a therapy that restores the endocrine system, including the reproductive system. Cognitive behaviour therapy offers a holistic treatment that is safe, cost effective, and easy to implement."
The team now intends to analyse further data from the pilot and to follow with a multi-centre trial involving a large number of women. "If the larger scale study confirms our earlier results," said Professor Berga, "we will have very strong evidence for offering stress reduction as an effective therapy for a significant group of infertile women."