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Hormonal Treatments for Women With Schizophrenia

  • Jayashri Kulkarni, PhD, MBBS, MPH
Jan 1, 2004
Volume: 
21
Issue: 
1
  • Schizophrenia, Geriatric Psychiatry, Schizophrenia Psychotic Features, Addiction, Alcohol Abuse

Emil Kraepelin proposed links between dementia praecox (schizophrenia) and hormones in 1892. Other early researchers, such as Hoskins, studied endocrine changes in people with schizophrenia at postmortem. The discovery of insulin further stimulated interest in the interaction between behavior and metabolism. Between 1940 and 1970, there was considerable interest in the psychoendocrinology of schizophrenia. Mason (1975) demonstrated the mimicking of psychotic symptoms by administering high doses of steroid hormones. Brambilla and Penati (1978) reviewed the evidence for malfunctioning of the adrenal, pituitary and thyroid glands and of the gonads in people with schizophrenia. Endocrinopathies were only rarely present, thus suggesting that endocrine abnormalities in these patients are not the cause of schizophrenia. As the role of neurotransmitters in the regulation of pituitary hormone release via hypothalamic hormones becomes clearer, neuroendocrine studies in people with schizophrenia aim to use the pituitary gland as the "window to the brain." This involves using probes to modify the secretion of anterior pituitary hormones to detect abnormalities in tubero-infundibular pituitary function reflecting similar abnormalities in the mesolimbic system. Lieberman and Koreen (1993) concluded in a large review that the hypothalamic-pituitary-thyroid axis, in general, has not been shown to manifest disturbances in schizophrenia. Nevertheless, studies of growth hormone have tended to show a response to a wide variety of pharmacological probes (e.g., apomorphine [Uprima], tryptophan, fenfluramine [Pondimin], baclofen [Liofen, Lioresal], clonidine [Catapres], methylphenidate [Ritalin] and bromocriptine [Parlodel]), suggestive of enhanced noradrenergic activity in patients with schizophrenia compared with controls. A clear omission from the neuroendocrine studies described to date is the study of hormonal profiles in women with schizophrenia. Researchers have often excluded women because of a putative inability to control the variable fluctuating monthly hormonal cycles. In considering the relationship between gonadotrophin and other gonadal steroids and mental state in patients with schizophrenia, there are very few studies examining the female patient. Riecher-Rossler and colleagues (1994) studied 32 acutely psychotic women and found a significant excess of admissions in the premenstrual and menstruation phases with an inverse relationship between serum estradiol and severity of psychotic symptoms.

Estrogen Protection

Pioneering researchers in the area of gender differences in the onset, treatment and outcome of schizophrenia have proposed that, in women, estrogen may confer protection against the early onset of severe schizophrenia (Lewine, 1988; Seeman and Lang, 1990). These researchers have suggested that women are vulnerable to relapses of schizophrenia, or their first episode of illness, in the perimenopausal period when estrogen production diminishes. As articulated by Hafner and colleagues (1998), the hypothesis also encompasses early estrogen effects on the developing brain such that a structural effect of estrogen acting during brain maturation causes the delay of first onset schizophrenia in females. From puberty, this putative structural effect is reinforced by a functional effect. Fading estrogen secretion around menopause causes women predisposed for schizophrenia (but who until then had been protected by estrogens) to fall ill with late-onset schizophrenia. Essentially, the estrogen protection hypothesis is based on three broad lines of work: epidemiological studies, biological or basic science studies in animal models, and clinical studies (Hafner et al., 1998).

Epidemiology

A gender difference in the age at first admission, with women being older than men, was noted by Kraepelin (1913-1915). The finding was largely ignored until the late 1980s when Angermeyer and Kuhn (1988) confirmed the age difference at first admission in 50 out of 53 international studies. It is now widely accepted that males presenting with their first episode of schizophrenia are usually between the ages of 16 and 19 years, while women are up to five to 10 years older at first presentation.

Animal Models

Behrens and colleagues (1992) showed that estrogen has a complex action on the dopamine system in animals, but were able to conclude from a series of studies that estrogen downregulates dopamine transmission. This finding has been replicated in animals (Clopton and Gordon, 1986; Ferretti et al., 1992; Perry et al., 1981). More recently, Fink and colleagues (1999, 1998) have shown that estrogen induces a significant increase in 5-HT2A receptors and the serotonin transporter (SERT) in regions of the rat forebrain that are concerned with mental state mood, cognition, memory, emotion and neuroendocrine control in humans. The precise mechanism of the estrogen serotonin interaction is not yet clear. The net effect of the action of estrogen on 5-HT2A receptors and SERT dopamine in general could be thought to mimic so-called atypical or newer antipsychotic medications. The significance of these findings for schizophrenia suggests that in fact the effect of estrogen in the brain on key neurotransmitter systems involved in the production of psychotic symptoms accounts for the estrogen protection hypothesis.

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References: 

References
1.

Alves SE, Weiland NG, Hayashi S, McEwen BS (1998), Immunocytochemical localization of nuclear estrogen receptors and progestin receptors within the rat dorsal raphe nucleus. J Compr Neurol 391(3):322-334.
2.

Angermeyer MC, Kuhn L (1988), Gender differences in age at onset of schizophrenia. An overview. Eur Arch Psychiatry Neurol Sci 237(6):351-364.
3.

Behrens S, Hafner H, DeVry J, Gattaz WF (1992), Estradiol attenuates dopamine-mediated behaviour in rats: implications for sex differences in schizophrenia. Pharmacopsychiatry 25(2):96.
4.

Berlin FS, Berger GK, Money J (1982), Periodic psychosis of puberty: a case report. Am J Psychiatry 139(1):119-120.
5.

Brambilla F, Penati G (1978), Perspectives in endocrine psychobiology. In: Perspectives in Endocrine Psychobiology. London: Wiley, pp309-422.
6.

Clopton J, Gordon JH (1986), In vivo effects of estrogen and 2-hydroxyestradiol on D-2 dopamine receptor agonist affinity states in rat striatum. J Neural Transm 66(1):13-20.
7.

Cone RI, Davis GA, Goy RW (1981), Effects of ovarian steroids on serotonin metabolism within grossly dissected and microdissected brain regions of the ovariectomized rat. Brain Res Bull 7(6):639-644.
8.

Dalton K (1980), Depression after Childbirth: How to Recognize and Treat Postnatal Illness. New York: Oxford University Press.
9.

Dennerstein L, Judd F, Davies B (1983), Psychosis and the menstrual cycle. Med J Aust 1(11):524-526.
10.

Endo M, Daiguji M, Asano Y et al. (1978), Periodic psychoses recurring in association with menstrual cycle. J Clin Psychiatry 39(5):456-461.
11.

Felthous AR, Robinson DB, Conroy RW (1980), Prevention of recurrent menstrual psychosis by an oral contraceptive. Am J Psychiatry 137(2):245-246.
12.

Ferretti C, Blengio M, Vigna I et al. (1992), Effects of estradiol on the ontogenesis of striatial dopamine D1 and D2 receptor sites in male and female rats. Brain Res 571(2):212-217.
13.

Fink G, Sumner BEH, McQueen JK et al. (1998), Sex steroid control of mood, mental state and memory. Clin Exp Pharmacol Physiol 25(10):764-775.
14.

Fink G, Sumner B, Rosie R et al. (1999), Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behav Brain Res 105(1):53-68.
15.

Hackmann E, Wirz-Justice A, Lichsteiner M (1973), The uptake of dopamine and serotonin in rat brain during progesterone decline. Psychopharmacologia 32(2):183-191.
16.

Hafner H, Maurer K, Loffler W et al. (1998), The ABC Schizophrenia Study: a preliminary overview of the results. Soc Psychiatry Psychiatr Epidemiol 33(8):380-386.
17.

Kraepelin E (1913-1915), Psychiatrie, liu lehrbuch fur studiereude und arzte. [Psychiatrie: Ein Lehrbuch fr Studierende und Žrzte.] Leipzig, Germany: JA Barth.
18.

Kulkarni J, de Castella A, Smith D et al. (1996), A clinical trial of the effects of estrogen in acutely psychotic women. Schizophr Res 20(3):247-252.
19.

Kulkarni J, Riedel A, de Castella A et al. (2001), Estrogen--a potential treatment for schizophrenia. Schizophr Res 48(1):137-144.
20.

Kulkarni J, McBain N, de Castella A et al. (2003), Presentation at Monash University Brain and Behaviour Institute Launch. Melbourne, Australia; Sept.
21.

Lewine RRJ (1988), Gender and schizophrenia.In: Handbook of Schizophrenia, vol. 3, Tsuang MT, Simpson JC, eds. New York: Elsevier, pp379-397.
22.

Lieberman JA, Koreen AR (1993), Neurochemistry and neuroendocrinology of schizophrenia: a selective review. Schizophr Bull 19(2):371-429.
23.

Mason JW (1975), Emotion as reflected in patterns of endocrine investigation. In: Emotions, Their Parameters and Measurement, Levi L, von Euler US, eds. New York: Raven Press, pp143-181.
24.

McEwen BS, Biegon A, Rainbow TC et al. (1981), The interaction of estrogens with intracellular receptors and with putative neurotransmitter receptors: implications for the mechanisms of activation of regulation of sexual behaviour and ovulation. In: Steroid Hormone Regulation of the Brain, Fuxe K, Gustafsson JA, Wetterberg L, eds. New York: Pergamon Press, pp15-29.
25.

Meyer PM, Powell LH, Wilson RS et al. (2003), A population-based longitudinal study of cognitive functioning in the menopausal transition. Neurology 61(6):801-806.
26.

Perry KO, Diamond BI, Fields JZ, Gordon JH (1981), Hypophysectomy induced hypersensitivity to dopamine: antagonism by estrogen. Brain Res 226(1-2):211-219.
27.

Riecher-Rossler A, Hafner H, Maurer K et al. (1992), Schizophrenic symptomatology varies with serum estradiol levels during menstrual cycle. Schizophr Res 6(2):114-115.
28.

Riecher-Rossler A, Hafner H, Stumbaum M et al. (1994), Can estradiol modulate schizophrenic symptomatology? Schizophr Bull 20(1):203-243.
29.

Seeman MV (1983), Interaction of sex, age, and neuroleptic dose. Compr Psychiatry 24(2):125-128.
30.

Seeman MV, Lang M (1990), The role of estrogens in schizophrenia gender differences. Schizophr Bull 16(2):185-194.
31.

Solthau A, Taylor R (1982), Depression after childbirth. Br Med J 284(6320):980-981.
32.

Wassertheil-Smoller S, Hendrix SL, Limacher M et al. (2003), Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 289(20):2673-2684 [see comment].

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