Hypothalamic‐pituitary‐gonadal axis in major depressive disorders

Capio S:t Görans sjukhus, Tukholma, Stockholm, Sweden
Acta Psychiatrica Scandinavica (Impact Factor: 5.61). 09/1988; 78(2):138-46. DOI: 10.1111/j.1600-0447.1988.tb06313.x
Source: PubMed


The baseline LH, FSH and testosterone levels and the LH and FSH response to TRH-LHRH administration (delta LH, delta FSH) were investigated in 28 patients meeting the RDC criteria for an acute major depressive disorder, and in 20 healthy persons. Twenty-two patients were also reinvestigated in a state of complete or partial clinical remission. Cross-sectional and longitudinal comparisons were made between the groups divided according to sex and menopausal status. After mathematical correction for age differences, the depressed males with an abnormal DST response showed significantly (P less than 0.03) higher delta FSH in the acute state compared to the controls. No relation could be established between the HPG axis hormone levels and the nocturnal serum melatonin levels or the PRL or TSH response to TRH-LHRH administration. In the longitudinal part of the study, the depressed males with an abnormal DST response showed decreased (P less than 0.03) testosterone levels and increased delta FSH (n.s.) in the acute state compared to remission, in contrast to the males with a normal DST. The present results do not support a hypothesis regarding a stimulus-induced down-regulation of the pituitary LHRH receptors in our patients. The possible mechanisms by which HPA axis activation (as revealed by an abnormal DST response) could influence the HPG axis in depressed patients remain to be elucidated.

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    • "Whereas the average blood levels of reproductive hormones are found mostly normal in women with depression (O'Toole and Rubin, 1995; Unden et al., 1988; Winokur et al., 1982; Young et al., 2000a,b), little is known about their diurnal rhythms. Recently, the authors have demonstrated that the normally cycling women who are living their usual lives have obvious diurnal estradiol rhythms (Bao et al., 2003). "
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    ABSTRACT: To investigate whether depression is accompanied by changes in diurnal rhythms of free estradiol and cortisol in different phases of the menstrual cycle, we measured these two hormone levels in saliva samples collected every 2 h for 24 h from 15 healthy normally cycling women and 12 age-matched normally cycling women suffering from major depression taking antidepressants. The assessments were repeated four times over one menstrual cycle: during menstruation and in the late follicular/peri-ovulating, early to mid-luteal and late luteal phases, respectively. Quantification with a nonlinear periodic regression model revealed distinct diurnal rhythms in free estradiol and free cortisol in all subjects. For the diurnal cortisol rhythm, significant differences were found in the peak-width and ultradian amplitude among different menstrual phases, both in controls and depressed patients, while no significant differences were found between the two groups. The diurnal estradiol rhythm, on the other hand, was quite consistent among different menstrual phases within both groups, while the depressed patients had overall larger amplitudes than controls, which is negatively correlated with disease duration. Significant positive correlations between the two hormone rhythms were found for 24-h mean level (mesor), peak, and trough in late luteal phase, and for ultradian harmonics in early to mid-luteal phase in controls, but only for ultradian harmonics in late follicular/peri-ovulating phase and for acrophase in the menstruation phase in depressed patients. A sub-analysis was also performed in patients who received Fluoxetine (n = 7). The findings implicate a close correlation between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis, both of which may be involved in depression.
    Full-text · Article · Mar 2004 · Hormones and Behavior
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    • "Men with depression have decreased testosterone levels (Unden et al., 1988; Schweiger et al., 1999). Testosterone levels as well as the number of CAG repeats within the AR gene were signi®cantly associated with depression (Seidman et al., 2001a). "
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    ABSTRACT: Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial in some elderly males with low-normal testosterone levels. However, at this point in time, widespread use of testosterone in an elderly male population outside controlled clinical trials seems inappropriate.
    Preview · Article · Jan 2004 · Human Reproduction Update
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    • "Among elderly men, lower testosterone levels were associated with depressive symptoms (Beck Depression Inventory scores, Barrett-Connor et al., 1999) or dysthymic disorder (Seidman et al., 2002). Moreover, lower testosterone levels were reported in men with depression independently of age (Vogel et al., 1978; Yesavage et al., 1985; Rupprecht et al., 1988; Unden et al., 1988; Steiger et al., 1991; Davies et al., 1992; Schweiger et al., 1999). In contrast, some studies did not observe any significant difference in testosterone levels between depressed men and controls (Sachar et al., 1973; Amsterdam et al., 1981; Levitt and Joffe, 1988; Mason et al., 1988; Rubin et al., 1989; Davies et al., 1992). "
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    ABSTRACT: This study examined the psychological symptomatology of men diagnosed with andropause and the association between calculated free testosterone (T) and depressed mood, anxiety and quality of life. Subjects were 153 men, aged 50-70 years, who participated in a screening of andropause. Total testosterone, FSH, LH and SHBG levels were measured. Depressed mood was assessed with the Carroll Rating Scale, anxiety with the "anxiety-insomnia" dimension of the General Health Questionnaire, and quality of life with the World Health Organisation Quality of Life questionnaire. The results showed that levels of free T decreased with age, whereas FSH and LH increased. Carroll Rating Scale scores were higher among hypogonadal subjects, but the mean score was low and not pathological. A negative correlation was observed between severity of depression as assessed by the Carroll Rating Scale and free T levels. However, subjects with a significant score on this scale did not exhibit different free T levels compared to subjects with a non-significant depressive score. Anxiety and quality of life did not differ between hypogonadal and eugonadal subjects. The present study therefore suggests that andropause is not characterised by specific psychological symptoms, but may be associated with "depressive symptoms" that are not considered as pathological.
    Full-text · Article · Nov 2003 · Psychoneuroendocrinology
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