Psychoneuroendocrine stress responses and mood as related to the menstrual cycle

Psychoneuroendocrine stress responses were studied in normally ovulating women in the follicular, ovulatory, and luteal phases of two consecutive menstrual cycles. Psychologic stress was induced by having the subjects perform a battery of cognitive tasks under time pressure. Blood samples were drawn after each session for radioimmunoassay of 17 beta-estradiol, progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, prolactin, cortisol, and androstenedione. Urine samples were obtained for estimation of adrenaline, noradrenaline, and cortisol. The results showed that psychoneuroendocrine stress responses as estimated by urinary excretion of adrenaline and noradrenaline varied significantly across the menstrual cycle, the highest values being obtained in the luteal phase. Self-reported mood and somatic symptoms showed distinct phase-related changes, with more negative mood states predominating in the luteal and menstrual phases and increased positive mood states in the follicular and ovulatory phases.     

Psychoendocrine response to sexual arousal in human males

The hypothesis is tested that luteinizing hormone (LH) and follicle stimulating hormone (FSH( may be released from the anterior pituitary in response to a psychological state of sexual arousal. LH levels in 10 male volunteers were found to be higher after viewing a sexually arousing film than after a control film. The magnitude of LH response was found to be positively correlated with the subjective evaluation of sexual arousal. FSH levels tended in the same direction bu the predominant and unexpected finding for this hormone was that levels were consistently lower during the first session, when anxiety was high, and higher during the second session, when anxiety was less, whether control or stimulus film had been shown. This study is analogous to those demonstrating the responsiveness of other anterior pituitary hormones to specific psychological states.     

Cystic ovaries in women affected with hereditary angioedema.

Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic-pituitary) abnormality, including high plasma beta-endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (HANE) during attacks as well as during symptom-free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HANE who were not on oral contraceptives. We have found PCO in 5/13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.     

Breast cyst fluid concentrations of beta-endorphin, steroids and gonadotrophins in premenopausal women with gross cystic disease

Breast cyst fluid (BCF) and plasma levels of beta-endorphin (beta-EP), oestradiol (E2), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), prolactin (PRL) and cortisol were assayed radiochemically in a group of 10 premenopausal women aged 45-50 years suffering from gross cystic breast disease. The concentration of beta-EP (fmol/ml) in BCF (17.6 +/- 4.6 S.E.) was over four times higher than that in plasma (4.2 +/- 0.5 S.E.). The level of E2 was 41 times higher (1738.2 +/- 350.5 S.E. pg/ml) and that of P was 47 times higher (65.47 +/- 8.25 S.E. ng/ml) in BCF than in plasma. The significantly increased values of beta-EP, E2 and P in BCF and the identification of beta-EP in the cyst-lining epithelium indicated that local synthesis occurs. Growth factor-like properties of beta-EP and E2 are responsible for the propagation of cystic changes. The autonomous formation and activity of beta-EP, E2 and P in cystic formations were not correlated with LH, FSH, TSH and cortisol levels, which were significantly higher in plasma than in BCF. The concentration of PRL in BCF was not significantly higher than that in plasma. Moreover, the plasma concentrations of testosterone, androstenedione, thyroxine, triiodothyronine, thyroxine-binding globulin and sex-hormone-binding globulin were within the normal ranges. In this study we demonstrated synergism between beta-EP and steroid hormones which encourages the development of gross cystic disease in premenopausal women.     

Emotional perception and neuroendocrine changes

The present study was designed to investigate the neuroendocrine modifications during affective states. In particular, we investigate if the pleasantness of the stimuli has a different effect on neuroendocrine responses. To address this issue, we compared the effects of pleasant, neutral, and unpleasant pictures on catecholamine, adrenocorticotrophic hormone (ACTH), cortisol, and prolactin plasma levels. Ten male participants were submitted to three experimental sessions, each on one of the three experimental days, a week apart in a counterbalanced order. Although in the subjective arousal rating, pleasant (erotic pictures) and unpleasant stimuli (pictures of mutilated bodies) receive the same high score, a different neuroendocrine pattern was obtained: unpleasant stimuli elicited a decrease in prolactin concentration and increases in noradrenaline, cortisol, and ACTH levels, whereas pleasant slide set viewing induced an increase in prolactin levels. The results suggest that the neuroendocrine system responds selectively to affective motivationally relevant pictures.     

A sex difference in features that elicit genital response

Previous research suggests that women's genital arousal is an automatic response to sexual stimuli, whereas men's genital arousal is dependent upon stimulus features specific to their sexual interests. In this study, we tested the hypothesis that a nonhuman sexual stimulus would elicit a genital response in women but not in men. Eighteen heterosexual women and 18 heterosexual men viewed seven sexual film stimuli, six human films and one nonhuman primate film, while measurements of genital and subjective sexual arousal were recorded. Women showed small increases in genital arousal to the nonhuman stimulus and large increases in genital arousal to both human male and female stimuli. Men did not show any genital arousal to the nonhuman stimulus and demonstrated a category-specific pattern of arousal to the human stimuli that corresponded to their stated sexual orientation. These results suggest that stimulus features necessary to evoke genital arousal are much less specific in women than in men.     

The relationship between pituitary-gonadal function and sexual behavior in healthy aging men

Few studies have assessed the role of pituitary and gonadal hormones on age-related changes in sexual behavior in healthy men. We conducted a retrospective and prospective evaluation of sexual function and behavior in 77 healthy married men aged 45 to 74 years. The subjects were studied in the sleep laboratory for four nights with the last night devoted to sequential blood sampling every 20 minutes. Significant age-related decreases in sexual desire, sexual arousal and activity, and increases in erectile problems were noted. Aging was negatively correlated with bioavailable testosterone (bT), was positively correlated with luteinizing hormone (LH), and was not related to total testosterone, estradiol, and prolactin. Bioavailable testosterone, and the ratio of bT over LH showed a close association with several sexual behavior dimensions while total testosterone, estradiol, and prolactin demonstrated few or no behavioral relationships. The age-related effect of bT was, however, a more important determinant of the reported behavioral differences than were the effect of bT independent of age. There was no evidence that changes in circulating hormones contribute to erectile disorders in healthy aging men.     

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.     

Changes in sexual behavior as a function of plasma sex steroid levels in post-menopausal women

Eight women who had been maintained on a combined estrogen-androgen drug since hysterectomy and bilateral oophorectomy 2 yr previously were investigated for changes in sexual behavior during the course of 1 treatment cycle. Following intramuscular injection of both sex steroids, plasma estradiol levels were within the normal range of young, cycling women but plasma testosterone exceeded the upper limit of normal female values. Sexual motivational behaviors (desire, fantasies and arousal) covaried with plasma steroid levels. Rates of coitus and orgasm, however, were unrelated to the changing levels of circulating hormones. A differential effect of the sex steroids on various aspects of sexual functioning was thus confirmed.     

Evaluation of neuroendocrine status in longevity

It is well known that physiological changes in the neuroendocrine system may be related to the process of aging. To assess neuroendocrine status in aging humans we studied a group of 155 women including 78 extremely old women (centenarians) aged 100-115 years, 21 early elderly women aged 64-67 years, 21 postmenopausal women aged 50-60 years and 35 younger women aged 20-50 years. Plasma NPY, leptin, glucose, insulin and lipid profiles were evaluated, and serum concentrations of pituitary, adrenal and thyroid hormones were measured. Our data revealed several differences in the neuroendocrine and metabolic status of centenarians, compared with other age groups, including the lowest serum concentrations of leptin, insulin and T3, and the highest values for prolactin. We failed to find any significant differences in TSH and cortisol levels. On the other hand, LH and FSH levels were comparable with those in the elderly and postmenopausal groups, but they were significantly higher than in younger subjects. GH concentrations in centenarians were lower than in younger women. NPY values were highest in the elderly group and lowest in young subjects. We conclude that the neuroendocrine status in centenarians is markedly different from that found in early elderly or young women.     

Evaluation of hypothalamic-pituitary-adrenal axis in amenorrhoeic women with insulin-dependent diabetes

Diabetes is associated with a higher incidence of secondary hypogonadotrophic amenorrhoea. In amenorrhoeic women with insulin-dependent diabetes a derangement in hypothalamic-pituitary-ovary axis has been proposed. No data exist on hypothalamic-pituitary-adrenal function in these women. Gonadotrophin releasing hormone (GnRH), corticotrophin releasing hormone (CRH), metoclopramide and thyroid releasing hormone (TRH) tests were performed in 15 diabetic women, eight amenorrhoeic (AD) and seven eumenorrhoeic (ED). Frequent blood samples were taken during 24 h to evaluate cortisol plasma concentrations. There were no differences between the groups in body mass index, duration of diabetes, insulin dose and metabolic control. The AD women had lower plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, oestradiol, androstenedione and 17-hydroxyprogesterone (17-OHP) than the ED women. The responses of pituitary gonadotrophins to GnRH, and of thyroid stimulating hormone (TSH) to TRH, were similar in both groups. The AD women had a lower prolactin response to TRH and metoclopramide, and lower ACTH and cortisol responses to CRH, than the ED women. Mean cortisol concentrations > 24 h were higher in the amenorrhoeic group. Significant differences in cortisol concentrations from 2400 to 1000 h were found between the two groups. Insulin-dependent diabetes may involve mild chronic hypercortisolism which may affect metabolic control. Stress-induced activation of the hypothalamic-pituitary-adrenal axis would increase hypothalamic secretion of CRH. This would lead directly and perhaps also indirectly by increasing dopaminergic tonus to inhibition of GnRH secretion and hence hypogonadotrophic amenorrhoea. Amenorrhoea associated with metabolically controlled insulin-dependent diabetes is a form of functional hypothalamic amenorrhoea that requires pharmacological and psychological management.     

Adrenal-medullary and adrenal-cortical responses to understimulation and overstimulation: comparison between type A and type B persons

Male and female university students, classified as Type A and Type B persons with the aid of a questionnaire measuring coronary-prone behavior, were studied while doing mental work under laboratory conditions, characterized by understimulation and overstimulation, and while unoccupied (baseline session). The urinary excretion of adrenaline, noradrenaline and cortisol, heart rate (in the understimulation and baseline conditions) and self-reports were used as indices of arousal. The overall picture showed that both experimental conditions increased arousal, the rise being particularly pronounced for cortisol excretion during understimulation and for adrenaline excretion during overstimulation. Comparison between groups showed that cortisol excretion was higher in Type A than in Type B persons of both sexes during understimulation. Adrenaline excretion was about the same in both sexes (Type A and Type B) during understimulation, but was higher in males than in females during overstimulation. There were no group differences in performance.     

The post-orgasmic prolactin increase following intercourse is greater than following masturbation and suggests greater satiety

Research indicates that prolactin increases following orgasm are involved in a feedback loop that serves to decrease arousal through inhibitory central dopaminergic and probably peripheral processes. The magnitude of post-orgasmic prolactin increase is thus a neurohormonal index of sexual satiety. Using data from three studies of men and women engaging in masturbation or penile-vaginal intercourse to orgasm in the laboratory, we report that for both sexes (adjusted for prolactin changes in a non-sexual control condition), the magnitude of prolactin increase following intercourse is 400% greater than that following masturbation. The results are interpreted as an indication of intercourse being more physiologically satisfying than masturbation, and discussed in light of prior research reporting greater physiological and psychological benefits associated with coitus than with any other sexual activities.     

Endocrine responses and examination anxiety

Endocrine and psychological function (measuring both affect and attitudes to study) were studied in 38 male medical students 4 weeks and 1-2 h before a major examination. Anxiety (or tension) and emotionality increased just before the examination, as did the 'denial' subscale of a 'coping' questionnaire. Serum cortisol and prolactin increased; serum testosterone and LH were unchanged. Both urinary noradrenaline and adrenaline were elevated. Increased cortisol correlated with increased prolactin across subjects; so, too, did levels of urinary noradrenaline and adrenaline, but the two sets of endocrine responses were not correlated with each other. Several of the trait scales predicted the endocrine response to the examination. The 'lie' scale of the Eysenck Personality Questionnaire correlated negatively with changes in both cortisol and prolactin, as did 'debilitating' anxiety, as defined by the Alpert-Haber scale. However, although there were no significant correlations between changes in hormone levels and those in any of the state scales, there was some relation between absolute hormone levels on the day of the examination. Measures of academic strategies or psychological responses to examinations do not predict the nature of the considerable hormonal response which occurs in this homogeneous set of high-achieving students.     

Elevated FSH concentrations in imminent ovarian failure are associated with higher FSH and LH pulse amplitude and response to GnRH

Imminent ovarian failure (IOF) in women is characterized by regular menstrual cycles and elevated early follicular phase FSH. This study explored underlying neuroendocrine causes of elevated FSH concentrations on day 3 of the menstrual cycle. The characteristics of episodic secretion of FSH and LH, the pituitary response to gonadotrophin-releasing hormone (GnRH), plasma oestradiol, and dimeric inhibin A and inhibin B on day 3 were compared in 13 women with elevated FSH concentrations (>10 IU/l) and 16 controls. FSH amplitudes were higher in the IOF group than in the controls (P < 0. 0001). The FSH pulse frequency did not differ between groups. The FSH response to GnRH was higher in the IOF patients than in the controls (P < 0.0001). Mean LH, LH amplitude and LH response to GnRH were higher in the IOF group, but LH pulse frequency did not differ between the groups. Concentrations of inhibin A and inhibin B were lower in the IOF group, while oestradiol showed no differences. We concluded that in women with IOF, the pituitary is more sensitive to GnRH. This leads to higher FSH and LH pulse amplitudes which underlie the elevated FSH concentrations in the early follicular phase.     

Differential effects of flurothyl- and electro-convulsive shock on sexual maturation and prolactin release in the rat

Summary The effects of single and repeated seizures on luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin secretion and on the onset of sexual maturation in rats are described. In addition, the influence of convulsions generated electrically (electroconvulsive shock, ECS) and chemically (using flurothyl) are compared. Repeated flurothyl convulsions and ECS (one daily convulsion from age 24 days) significantly delay vaginal opening in female rats. The incidence of first ovulation at maturation is reduced to 20% compared with 70–100% for untreated groups. Body and adrenal weights in immature rats are not modified by flurothyl convulsions. Repeated ECS does not influence adrenal weight although somatic growth is inhibited. In an effort to clarify the mechanism of action of convulsions on puberty onset, we examined acute changes in LH, FSH and prolactin secretion and the surge response of LH/FSH to gonadal steroid priming. A single flurothyl convulsion potently inhibits prolactin secretion. In contrast, an ECS acutely stimulates prolactin release in male and female rats. Convulsive seizures do not consistently alter tonic gonadotropin output. However, both flurothyl convulsions and ECS attenuate estradiol benzoate/progesterone-induced LH and FSH surges in ovariectomized rats though this is apparently not mediated by dopamine/prolactin since bromocriptine treatment delays sexual maturation without preventing ovulation at first estrus. Similarly, bromocriptine does not disrupt LH/FSH surges induced by gonadal steroid treatment. One component in the neural response to convulsions may be hypothalamic endogenous opiate peptides since the ability of naloxone to influence LH and prolactin secretion is potentiated by repeated ECS. On the other hand, dopamine is clearly implicated in the flurothyl-induced inhibition of prolactin secretion, since haloperidol reverses this effect.     

Uncovering category specificity of genital sexual arousal in women: The critical role of analytic technique

Based on analytic techniques that collapse data into a single average value, it has been reported that women lack category specificity and show genital sexual arousal to a large range of sexual stimuli including those that both match and do not match their self‐reported sexual interests. These findings may be a methodological artifact of the way in which data are analyzed. This study examined whether using an analytic technique that models data over time would yield different results. Across two studies, heterosexual (N = 19) and lesbian (N = 14) women viewed erotic films featuring heterosexual, lesbian, and gay male couples, respectively, as their physiological sexual arousal was assessed with vaginal photoplethysmography. Data analysis with traditional methods comparing average genital arousal between films failed to detect specificity of genital arousal for either group. When data were analyzed with smoothing regression splines and a within‐subjects approach, both heterosexual and lesbian women demonstrated different patterns of genital sexual arousal to the different types of erotic films, suggesting that sophisticated statistical techniques may be necessary to more fully understand women's genital sexual arousal response. Heterosexual women showed category‐specific genital sexual arousal. Lesbian women showed higher arousal to the heterosexual film than the other films. However, within subjects, lesbian women showed significantly different arousal responses suggesting that lesbian women's genital arousal discriminates between different categories of stimuli at the individual level. Implications for the future use of vaginal photoplethysmography as a diagnostic tool of sexual preferences in clinical and forensic settings are discussed.     

Plasma catecholamines and pituitary adrenal hormones related to mental task demand under quiet and noise conditions

Plasma levels of catecholamines and pituitary adrenal hormones were measured in 20 min samples from eight subjects, in one control session and two experimental sessions, while they performed a short-term memory task under quiet or noise conditions.

Performing the task led to significant increase in the plasma levels of cortisol, adrenaline and noradrenaline, whereas no variations in growth hormone and dopamine were observed. Similarly, significant changes occurred in urinary catecholamine excretion. A significant correlation was found between individual plasma cortisol increments and error-rates assessed from an accuracy of recall variable. For adrenaline and noradrenaline, an early response apparently linked with an anticipatory process preceded the task. Exposure to noise did slightly amplify cortisol response to the task, but during the first experimental session, with or without noise, the task elicited greater cortisol increases in all subjects than during the second session.

These results provide evidence for a relationship between sympathoadrenocortical activity and attentional demand, whereas cortisol increments seem to be more specifically related to better coping with the task. Frequent hormone level measurements during a prolonged mental task might clarify the complex relationship between time-related bodily hormonal changes, performance and subjective feelings.     

Factors affecting reproductive hormones in HIV-infected, substance-using middle-aged women

OBJECTIVE: To determine whether reproductive hormone levels are affected by human immunodeficiency virus (HIV) and drug use. DESIGN: HIV-infected and uninfected women (N=429), median age 45, were interviewed on menstrual frequency, demographic and psychosocial characteristics, and drug use behaviors. Serum was obtained on cycle days 1 to 5 in women reporting regular menses. Premenopausal-, early menopausal, and late menopausal transition and postmenopausal stages were assigned based on menstrual history. Serum was assayed for follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), prolactin, thyroid-stimulating hormone, and inhibin B. Body mass index, HIV serostatus, and CD4+ counts were measured. Factors associated with hormone concentrations were assessed using uni- and multivariable analyses. Hormone concentrations were compared within menstrual status categories using nonparametric comparisons of means. RESULTS: In this cross-sectional analysis, LH and FSH increased, and E2 and inhibin B were significantly lower in women of older age and more advanced menopausal status. Increased body mass index was strongly associated with decreased LH. Opiate use was significantly associated with lower inhibin B and E2 and increased prolactin. Poorer self-rated health was statistically significantly associated with lower LH and FSH, but increased education was associated with higher LH and FSH. Among HIV-seropositive women, opiate users had detectably lower FSH and LH than nonusers, and use of highly active antiretroviral therapy was significantly related to higher LH, FSH, and E2, whereas cocaine use was associated with lower E2. CONCLUSIONS: Age and menopausal status are strongly related to reproductive hormones. Body mass index and use of opiates, cocaine, and highly active antiretroviral therapy as well as educational attainment and perceived health can significantly modify reproductive hormones during the menopausal transition and need to be considered when interpreting hormone levels in middle-aged women.     

Interactions of oestrogens and hours of sleep on cortisol,FSH, LH,and prolactin in hypogonadal women

The effects of conjugated oestrogens 0.625 mg and placebo on adrenal and pituitary hormones were compared in 10 postmenopausal women during their sleep by means of a double blind prospective crossover study. On placebo, the women had nocturnal variations in LH, prolactin and cortisol concentrations. However, oestrogen administration selectively blunted LH and prolactin changes, but not the rise in cortisol.