Issue: Reproductive hormones have profound behavioral effects. Actions of estrogen, progesterone, and testosterone may be useful adjuncts to psychotropic medication.
|The remarkable benefits
of estrogen replacement therapy in preventing
cardiovascular illness and osteoporosis in postmenopausal
women are well known. However, hormone replacement
therapy is not just for the women's health physician to
prescribe. Recent advances in neurobiology have
demonstrated that estrogen exerts dramatic effects on the
central nervous system (CNS).1,2 Psychiatrists
are beginning to exploit this fact to benefit women with
psychiatric disorders, especially depression.
By targeting key receptors in the CNS, reproductive hormones modulate diverse behaviors such as mood, cognition, and libido.2 Thus, sex hormones are neuromodulators. It is not surprising, therefore, that these behaviors can change as reproductive hormones change across the normal life cycle. Premenstrual irritability, postpartum "blues," and perimenopausal mood swings may all represent behavioral fluctuations linked to shifts in reproductive hormone levels.2
Additionally, shifts in reproductive hormones can herald the onset of psychiatric disorders.2 This shift is exemplified by the impressive link between episodes of affective disorder and the normal female life cycle.3 Women have about the same rate of new onset of major depressive disorder as men both before puberty and after menopause. The rate skyrockets, however, for women of childbearing potential, with slight decreases during pregnancy and peak increases postpartum and in the 5- to 7-year perimenopausal period prior to the complete cessation of menses.2,3
|Recalling that mental
illness may be damaging to your brain,4 a
major affective episode linked to any shift in
reproductive hormones greatly increases the risk of
recurrence during a subsequent shift in reproductive
hormones, a phenomenon known as kindling.5
Also, estrogen replacement therapy may significantly
reduce a postmenopausal woman's risk for developing
Alzheimer's disease.2,6 Thus, preventing
episodes of mental illness by anticipating them in high
risk periods of the life cycle is becoming a
The use of reproductive hormones to augment psychotropic drugs is in its infancy, with an embarrassing lack of controlled clinical trials. Until these are available, use of reproductive hormones as partners to antidepressants will proceed by art and anecdote perhaps more than by science. Although estrogen replacement therapy is not profoundly antidepressant, it convincingly diminishes mood fluctuations in perimenopause, especially when accompanied by vasomotor instability.2,6 Estrogen replacement therapy can, on occasion, successfully augment antidepressants in women who have treatment-resistant depression, but it is impossible to predict in which perimenopausal treatment-resistant women this treatment will work.6 Clinicians have the sense, however, that estrogen replacement therapy produces a quicker antidepressive response (i.e., days) than do antidepressants alone (i.e., weeks). Efficacious hormone therapy includes both estrogen-containing oral contraceptives for early perimenopausal women and estrogen replacement therapy for late perimenopausal women.2,6
|Progestins can be a
psychiatrist's enemy.2,6 Not only can they be
associated with menstrual magnification and profound mood
swings in women routinely taking progestins for
contraception or for hormone replacement therapy, they
can even precipitate a new affective episode in the
vulnerable. Thus, one psychiatric intervention is to
avoid or withdraw progestins is such patients when
possible. Another alternative is to give
estrogen/progestin combinations (either oral
contraceptives or hormone replacement therapy) without
interruption rather than use the traditional cyclical
regimen, where the serum hormone levels fluctuate.
Constant delivery of hormone replacement therapy may
smooth out behaviors and provide a stable platform onto
which to superimpose antidepressants.2,6
Finally, administration of testosterone to both men and
women can have striking behavioral effects, both desired
and undesired. Guidelines for psychiatric use of
androgens are sorely needed.
This is indeed an exciting era as psychiatry expands its frontiers into the use of reproductive hormones to prevent and treat mood disorders and even Alzheimer's disease. Sex hormones have become attractive partners for the modern psychiatrist.
Brainstorms aims to provide updates of novel concepts emerging from the neurosciences that have relevance to practitioners.
From the Clinical Neuroscience Research Center in San Diego and the Department of Psychiatry at the University of California San Diego.
|1. Stahl SM. Estrogen makes the brain a sex organ
[Brainstorms]. J Clin Psychiatry 1997;58:381-382
2. Jensvold MF, Halbreich U, Hamilton JA, eds. Psychopharmacology and Women: Sex, Gender and Hormones. Washington, DC: American Psychiatric Press; 1996
3. Weissman MM. Epidemiology of major depression in women. In: Syllabus & Proceedings Summary presented at the 1996 annual meeting of the American Psychiatric Association; May 4-9, 1996; New York, NY. No. 5C:285
|4. Stahl SM. Mental illness
may be damaging to your brain [Brainstorms]. J Clin
5. Parry B. Reproductive related depressions in women: phenomena of hormonal kindling? In: Hamilton JA, Harberger PN, eds. Postpartum Psychiatric Illness: A Picture Puzzle. Philadelphia, Pa: University of Pennsylvania Press; 1992:200-218
6. Stahl SM. Reproductive Hormones as Adjuncts to Psychotropic Medication: Directions in Psychiatry. New York, NY: Hatherleigh Press. In press