Donald M. Broverman

Roles of the gonadal steroid hormones in psychiatric depression in men and women

Abstract 1. 1. Depressed men and women who fail to respond to conventional antidepressant treatment show significant alleviation of depressive symptoms when treated with high doses of gonadal steroids (conjugated oral estrogen in women; mesterolone in men). 2. 2. Depression in men is accompanied by a high production of estradiol; and depression in women is accompanied by higher production of testosterone. Whether these findings are related to the therapeutic effects of gonadal hormones upon depression are unknown.

Relationships of serum estradiol levels, menopausal duration, and mood during hormonal replacement therapy

A study was undertaken in 38 menopausal women on-cyclic HRT (estropipate) and estropipate + nor-ethindrone). Serum estradiol levels during treatment were related to mood changes and platelet MAO activity. The relationship between serum estradiol levels and mood changes was found to be a function of the duration of menopause. Women with a short duration of menopause (12.9 months +/- 6.1) were compared to women with a long duration of menopause (76.6 months +/- 52.3). Women with a short duration of menopause had significantly lower mean serum estradiol levels during HRT compared to women with a long duration of menopause (216.9 +/- 62.3 vs. 291.13 +/- 118.12, respectively, p < .02). It had previously been reported that estrogen treatment in menopausal women had a positive effect on mood, whereas the combination of estrogen plus a progestin had a negative effect on mood. We found that the women with a long duration of menopause and higher treatment serum estradiol levels had significantly more dysphoria when receiving a combination of estrogen plus progestin than did the women with a short duration of menopause and lower serum estradiol levels. However, both short and long duration menopausal groups showed improvement in mood when estrogen was administered alone. Platelet MAO levels, a marker of adrenergic and serotonergic function thought to relate to mood, were negatively correlated with serum estradiol levels during HRT. We suggest that these paradoxical findings may be secondary to a prolonged estrogen deficiency state in women with a long duration of menopause.

Serum estradiol levels in male cigarette smokers.

Serum estradiol levels were compared in smoking and nonsmoking men in two separate samples. Sample I consisted of 41 young adult male volunteers ranging in age from 18 to 24 years. Twenty-three men smoked an average of 24.5 +/- 6.9 cigarettes daily. The duration of smoking averaged 5.2 +/- 2.2 years. Sample II consisted of 35 husbands who had been evaluated for infertility; they ranged in age from 19 to 49 years. Eighteen men smoked an average of 21.6 +/- 7.9 cigarettes daily. The duration of smoking averaged 11.5 +/- 4.5 years. Age, height, and weight did not differ significantly between smokers and nonsmokers within either group. Serum estradiol levels were significantly elevated in smokers compared with nonsmokers in both groups (p less than 0.001 and p less than 0.0001 in Samples I and II, respectively). No significant correlations were found between serum estradiol levels and the number of cigarettes smoked daily, or with the duration of smoking in either sample. The differences in serum estradiol levels between smokers and nonsmokers could not be attributed to the differences in marijuana and alcohol use that existed between the smokers and nonsmokers in each sample. The recent reports of elevated serum estradiol levels as a possible risk factor in coronary heart disease are discussed in view of the known relationship of cigarette smoking to coronary heart disease.

Serum estrogen levels in men with acute myocardial infarction

Serum estradiol and serum estrone levels were assessed in 29 men in 14 men in whom myocardial infarction was ruled out; in 12 men without apparent coronary heart disease but hospitalized in an intensive care unit; and in 28 men who were not hospitalized and who acted as control subjects. (The 12 men who were hospitalized but who did not have coronary heart disease were included to control for physical and emotional stress of a severe medical illness.) Ages ranged from 21 to 56 years. Age, height, and weight did not differ significantly among groups. Blood samples were obtained in the patient groups on each of the first three days of hospitalization. The serum estrone level was significantly elevated in all four patient groups when compared with that in the control group. Estrone level, then, did not differentiate patients with and without coronary heart disease. Serum estradiol levels were significantly elevated in the groups with myocardial infarction, unstable angina, and in the group in whom myocardial infarction was ruled out. However, estradiol levels were not significantly elevated in the group in the intensive care unit without coronary heart disease when compared to the level in the normal control group. Serum estradiol levels, then, were elevated in men with confirmed or suspected coronary heart disease but were not elevated in men without coronary heart disease even under the stressful conditions found in an intensive care unit. Serum estradiol levels were significantly and positively correlated (p less than 0.03) with serum total creatine phosphokinase levels in the patients with myocardial infarction. The five patients with myocardial infarction who died within 10 days of admission had markedly elevated serum estradiol levels. The potential significance of these serum estradiol elevations is discussed in terms of estradiols ability to enhance adrenergic neural activity and the resultant increase in myocardial oxygen demand.

EEG Responses in Regularly Menstruating Women and in Amenorrheic Women Treated with Ovarian Hormones

Electroencephalographic driving reponses to photic stimulation vary with the menstrual cycle and with manipulations of ovarian hormones thought to control the menstrual cycle. Estrogens reduce driving responses to photic stimulation, and estrogen plus progesterone enhance these responses. The electroencephalographic changes may reflect the effects of gonadal steroid hormones upon central adrenergic processes.

The Automatization Cognitive Style, androgens, and monoamine oxidase

Automatized behaviors are those behaviors which have been so highly practiced tha t minimums of mental and physical effort are required for their efficient execution. Such behaviors include the bulk of everyday activities, e.g. , keeping ones balance, walking, talking, reading, maintaining perceptual constancies, writing, etc. Early investigators (BlcYAN and HAI~TER, 1899 ; BOOK, 1925) argued tha t the automatizat ion of simple habits is a pre-requisite for the acquisition of new, more complex abilities. For instance, the ability to automatical ly recognize phonemes, the basic sounds of speech, may be necessary before facility in speech itself can develop (HUMPHlCEr, 1951). Empirically, automatizat ion ability has been found to be positively related to occupational level, i. e., normal adult males with strongly automatized routine behaviors were found to have higher level occupations than individuals with weakly automatized behaviors but of similar age, education, and intelligence (BI~ovEI~IAN, 1964).

Individual differences in changes in mood and platelet monoamine oxidase (MAO) activity during hormonal replacement therapy in menopausal women

Estrogen replacement treatment in menopausal women has been reported to have a positive effect on mood states. However, the addition of a progestin partially negates this positive effect in some women. The opposite effects of estrogen and progestin on mood may relate to their opposite effects on adrenergic and serotonergic neural function. In a double-blind, placebo-controlled, crossover study, 38 nondepressed menopausal women were cyclically treated with estrogen and estrogen plus progestin, or with placebo, for five 28-day cycles. This paper identifies the pretreatment attributes of women who do and do not have negative mood responses to progestin, and examines the relationship of these adverse side-effects to platelet monoamine oxidase (MAO), a marker of adrenergic and serotonergic functioning. Adverse mood responses to progestin occur in women with a long duration of menopause, low pretreatment serum estradiol and testosterone levels, high pretreatment serum FSH levels, low pretreatment platelet MAO activity, and pretreatment mood abnormalities. We conclude that adverse mood response to the addition of a progestin occurs in menopausal women who have low pretreatment gonadal hormone levels secondary to a long duration of menopause. Impaired central nervous system adrenergic and serotonergic functioning also may be a factor predisposing to a negative mood response to progestin.

Family Size and Sex-Role Stereotypes

Social attitudes about sex roles have been implicated as important factors in population growth. Degree of incorporation of stereotypic sex roles into the self-concepts of mothers is found to be related to completed family size.

Negative relationships between abilities

Abilities are usually assumed to exist in a “positive manifold.” Experimental manipulations of physiological variables, however, suggest that negative relationships exist between certain of the neural processes contributing to simple perceptual-motor vs. perceptual-restructuring tasks. First-order correlative evidence of this phenomenon cannot be obtained because the between-individual differences in general ability level tend to exceed the behavioral effects of the intra-individual opposition between neural processes. Also, since statistical removal of the “g” variance induces bipolarity in the remaining variance, the second-order negative correlations are necessarily regarded as artifactual. A combined correlational-experimental approach is suggested to overcome this difficulty.

Testosterone Effects upon Photic Stimulation of the Electroencephalogram (EEG) and Mental Performance of Humans

The effects of long-term testosterone administration on 3 poorly androgenized male adolescents were studied. In all three Ss, repeated measures were taken on EEG resistance to photic stimulation. This measure has previously been shown to be associated with level of arousal of the adrenergic system. In addition, on two Ss, repeated measures of ability to perform a highly practiced simple repetitive task called an “automatized” task were taken. This measure has previously been demonstrated to be associated with anthropometric indices of androgenicity. The design involved weekly measures of the dependent variables over the following conditions: pre-treatment, treatment with depo-testosterone, a double-blind placebo treatment (for 2 Ss), and a second depo-testosterone treatment (for the same 2 Ss). This was done over 20 to 40 wk. Results showed that in all 3 Ss there was a relationship between the testosterone administration and the EEG measure; that is, the androgen injections facilitated EEG resistance to photic stimulation. In 2 Ss given repeated measures on the automatized task, it was found that testosterone administration was also positively correlated with the ability to perform this task. These results suggest that testosterone acts in a way similar to a mild adrenergic stimulant.