Edward L. Klaiber

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.

Interrelationships of cigarette smoking, testicular varicoceles, and seminal fluid indexes *

Data on cigarette smoking, testicular varicoceles, seminal fluid indexes, and oligospermia were examined in 160 young men without known disease and in 94 husbands in infertile couples. The combination of smoking and testicular varicoceles is strongly related to the incidence of oligospermia, defined as sperm count less than or equal to 20 X 10(6)/ml, in each sample. Smokers with testicular varicoceles, in each sample, had a disproportionately high incidence of oligospermia. In the combined sample of 254 men, the smokers with testicular varicoceles had an incidence of oligospermia approximately ten times greater than that in nonsmokers with testicular varicoceles and approximately five times greater than that in men who smoked but were without testicular varicoceles. This relationship of cigarette smoking and testicular varicoceles to oligospermia has not been previously reported. The pathophysiologic basis of the interaction between smoking and varicoceles was theorized to be due to an increased secretion of catecholamines from the adrenal medulla, induced by cigarette smoking. The elevated catecholamine concentrations in the renal vein would then reach the testes via retrograde flow down the internal spermatic vein in men with testicular varicoceles, resulting in seminiferous tubule damage.

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.

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.

Dynamics of estradiol and testosterone and seminal fluid indexes in smokers and nonsmokers

The serum levels of estradiol (E2) and testosterone (T), the metabolic clearance rates of estradiol (MCRE2) and testosterone (MCRT), and the production rates of estradiol and testosterone (PRE2) and (PRT) were examined in 22 male smokers and 21 male nonsmokers. Seminal fluid indexes (sperm count, % motility, grade of motility, and % of sperm with abnormal morphology) were also assessed. The mean E2 level and the mean PRE2 were significantly greater in smokers than in nonsmokers (P less than 0.001 and P less than 0.01, respectively); however, the means of MCRE2, MCRT, PRT, and T did not differ significantly in smokers compared to nonsmokers. No significant product-moment correlations were found between the various hormonal measures and the seminal fluid indexes in the overall sample. However, the smokers with sperm counts below the median sperm count of the sample had significantly higher mean levels of E2 and PRE2 than did the smokers with sperm counts above that median. Mechanisms that might mediate the greater PRE2 of smokers and a negative relationship between estradiol and sperm count are discussed.

Plasma immunoreactive estrogens and LH during the menstrual cycle

Abstract Plasma immunoreactive estrogens and LH were measured daily when feasible during three normal cycles and one clomiphene-induced ovulatory cycle. In all the subjects studied, an estrogen peak preceded the midcycle LH peak. The above finding suggests that estrogens may play an important role in a midcycle surge of LH.

EEG driving responses as a function of monoamine oxidase.

Abstract EEG driving responses to photic stimulation were significantly reduced in ten normal young males following administration of isocarboxazid (Marplan), a monoamine oxidase inhibitor. Prior to drug administration. EEG driving responses were positively related to plasma monoamine oxidase activity levels. These results are interpreted as reflecting the effect of central adrenergic processes upon EEG driving responses to photic stimulation.

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.