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In our role as the guardian of reproductive health, we are called upon to understand how various conditions affect the reproductive tract and reproductive functioning. Time-honored interactions for which we are responsible include the effect of infectious agents, cancers, and medical conditions such as diabetes. Obviously, mental health also affects reproductive function, but our orientation often causes us to minimize the attention we pay to the effect of this domain upon obstetrical and gynecological conditions. We typically know a great deal about antibiotics but not as much about antipsychotics. The lesser attention often paid to mental health strikes me as odd, especially when one considers that there is probably nothing more contagious than emotion. A review of psychiatry and reproductive function is beyond the present scope, so the aim of this feature is to update you on emerging concepts regarding the comprehensive effect of stress upon reproductive functioning.
What is stress? A commonly accepted definition is that it is the elicitation by thoughts, emotions, or behaviors of increased cortisol secretion and increased sympathetic tone.1 Manifestations of stress include arousal and heightened vigilance. If the stress cannot be relieved or avoided and persists, then a state of chronic stress may evolve. One experimental paradigm for this is called "inescapable shock," and in laboratory animals, it can lead to behavioral paralysis and cessation of attempts to escape. Parallels have been drawn between this experimental paradigm and the development of psychiatric states such as anxiety, depression, and post-traumatic stress disorder. Recent progress in the field of behavioral neuroendocrinology has revealed that chronic stress elicits more than just increased sympathetic activity and elevations in cortisol. The entire neuroendocrine axis undergoes homeostatic rearrangement. First, vegetative functions, including appetite, are suppressed. The TSH response to TRH is blunted and thyronine and thyroxine levels fall to prevent the body from metabolizing itself. Hypervigilance and behavioral hyperactivity or paralysis and chronic anxiety can develop. Not surprisingly, GnRH drive is disrupted to save energy and divert attention to the perceived crisis or threat.2
It is easier to define the biology of the stress response than it is to understand what is a stressor. While the stressed state has often been dismissed as medically irrelevant, reductionistic definitions of what should qualify as a stressor have further contributed to the tendency to ignore the events or states that elicit the stress response. Metabolic states like starvation are easy to appreciate as stressors. On the other hand, psychological stressors can be exceedingly difficult to envision as such, if only because they are highly idiosyncratic and a matter of perception of self and others. Here we think of states such as self-fulfilling negative prophesies, want- ing more than is achievable, undue ambition, being heartsick or homesick, fear, grief, sense of instability, unmet dependency needs, and drive for autonomy as potential stressors embedded within and activated by the psychosocial framework of one’s existence. In the psychological domain, attitudes and interpretations have emerged as culprits in the paradigm of stress-induced anovulation.3 When dealing with infections, we want to define both the causative agent and the permissive factors in the host, such as immunosuppression or menstrual phase. The same approach applies to psychological agents; the host response, that is, their perceptions, gates the degree of biological activation. Therefore, we will not be able to help interrupt chronic stress unless we understand the host’s perspective.
Still, you may ask, why care? If fertility is not being sought and exogenous hormones are provided, why should the physician get involved in metaphysics? The answers to this query are just beginning to emerge. For instance, recent evidence reveals that acute endocrine arousal in the form of elevated cortisol levels impairs certain types of memory.4 Chronic stress may seriously impair our ability to process important information and therefore may preclude comprehensive decision-making. Chronic stress is thought to predispose to depression and dementia by altering the host, perhaps in irreversible ways.5 Ovulation induction in women with stress-induced anovulation may predispose not only to preterm delivery and poor fetal growth,6 but also to postpartum depression and poor psychosocial development of the children.7 The other important clinical point is that the biological correlates of chronic stress, particularly ongoing metabolic alterations,8 prevent bone accretion,9 may accelerate atherogenesis, and can trigger psychological decompensation. Just adding back the missing sex steroids is missing the point. It is difficult for me to imagine how we will provide comprehensive reproductive health care unless we learn to recognize the multiple manifestations of stress and institute appropriate interventions, such as helping women develop healthy attitudes and coping strategies.
Not all women with amenorrhea have stress as the cause. And, not all women with stress have amenorrhea, particularly if they are menopausal. In the case of amenorrhea, however, one should be certain to have a diagnosis before embarking upon the treatment plan. In caring for menopausal women, thought should be given to arranging psychological assessment if there are disturbing psychosomatic symptoms that do not respond to appropriate hormonal management.
1. Chrousos GP, Gold PW. JAMA 1992;267:1244-1252.
2. Berga SL, et al. J Clin Endocrinol Metab 1989;68: 301-308.
3. Giles DE, Berga SL. Fertil Steril 1993;60:486-492.
4. Lupien SJ. J Clin Endocrinol Metab 1997;82: 2070-2075.
5. Stein-Behrens B, et al. J Neurotics 1994;14:5373-5380.
6. Van der Spy ZM, et al. Br Med J 1988;296:962-965.
7. Pike KM, Rodin J. J Abnorm Psychol 1991;100: 198-204.
8. Argente J, et al. J Clin Endocrinol Metab 997;82: 2085-2092.
9. Klibanski AN, et al. J Clin Endocrinol Metab 1994;80:898-904.