Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurochemical brain changes across the menstrual cycle in five women with premenstrual dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times of complete absence and height of PMDD symptoms, respectively). The point resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in the medial frontal gray matter and in the occipito-parietal white matter. The ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal cortex and the cingulate gyrus declined significantly from the follicular to the luteal phase in both groups of subjects. The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward higher levels in the PMDD patients in the luteal phase of the menstrual cycle. Differences between PMDD and control subjects were not statistically significant. Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may influence the neurochemistry of brain activity in premenopausal women.

Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in women with premenstrual syndrome.

OBJECTIVE: To determine whether women with premenstrual syndrome (PMS) have aberrations of the GH axis as has been demonstrated in individuals with depression. DESIGN: Prospective trial. SETTING: Department of Obstetrics and Gynecology, University of California, Los Angeles. PATIENT(S): After prospective screening, 32 healthy women with PMS and 32 asymptomatic controls completed the study. INTERVENTION(S): Subjects completed a daily PMS symptom diary and a Beck Depression Inventory. They underwent phlebotomy 5 days and 12 days after the LH midcycle surge, which was identified with the use of a urinary LH detection kit. MAIN OUTCOME MEASURE(S): Serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), E2, and progesterone. RESULT(S): Levels of IGF-1, IGFBP-3, E2, and progesterone did not differ between women with prospectively documented PMS and control subjects. CONCLUSION(S): Premenstrual syndrome and affective disorder share common symptoms and possibly a common cause. Biochemical markers such as alterations in the somatotropic system often are associated with major depression. Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities.

Progesterone metabolite allopregnanolone in women with premenstrual syndrome.

OBJECTIVE: To evaluate the anxiolytic 3alpha-5alpha-reduced progesterone metabolite allopregnanolone in the luteal phase of the menstrual cycle in women with premenstrual syndrome (PMS) and controls. METHODS: Thirty-five women with prospectively documented PMS and 36 controls were evaluated. Serum progesterone and allopregnanolone levels were measured on days 19 and 26 of the cycle as determined by urinary LH detection kits. Analysis of variance and Student t tests were used to analyze the data. RESULTS: Allopregnanolone levels were significantly lower on day 26 in the PMS group than in controls (3.6 +/- 0.8 versus 7.5 +/- 1.3 ng/mL; P < .04). Significant differences in the ratio of the metabolite to progesterone also were noted, with a smaller ratio in the PMS subjects (0.9 +/- 0.3 versus 3.2 +/- 1.3 ng/mL; P < .05). There were no significant differences between the PMS and control groups with respect to serum progesterone levels. CONCLUSION: Subjects with PMS manifested lower levels of the anxiolytic metabolite allopregnanolone in the luteal phase when compared with controls. Diminished concentrations of allopregnanolone in women with PMS may lead to an inability to enhance gamma aminobutyric acid-mediated inhibition during states of altered central nervous system excitability, such as ovulation or physiologic or psychological stress. The lowered metabolite levels could contribute to the genesis of various mood symptoms of the disorder, such as anxiety, tension, and depression.

Cognitive functioning in premenstrual syndrome.

OBJECTIVE: To evaluate cognitive functioning in women with premenstrual syndrome (PMS) and controls during the follicular and luteal phases of the menstrual cycle. METHODS: Thirty women with PMS and 31 controls were selected on the basis of psychiatric interview and prospective daily diary recordings. Subjects were tested on two occasions, follicular (days 8-10) and luteal (days 24-26), using complex tasks consisting of measures validated previously for the assessment of "executive" frontal-lobe functions. Tests were counterbalanced for order across subjects. RESULTS: The Beck Depression Inventory scores were significantly different between the groups and across time (P < .001). Women with PMS had a mean luteal phase Beck score of 13.3 consistent with mild-to-moderate premenstrual depression. There were no statistically significant score differences in tests for attention, memory, cognitive flexibility, and overall mental agility. The evaluation of our preliminary data with 30 PMS subjects and 31 controls indicated a very small effect size (.02). To detect an effect size this small (if in fact one exists) with a power of .8 would require a sample of more than 1000 subjects per group. CONCLUSION: Our sample of women with PMS failed to demonstrate objective evidence of diminished cognitive performance, despite subjective feelings of inadequacy.

Decreased central opioid activity in premenstrual syndrome: luteinizing hormone response to naloxone.

OBJECTIVE: To evaluate central opioid activity in women with prospectively documented premenstrual syndrome (PMS) and control women in the mid- and late luteal phases of the menstrual cycle. METHODS: Blood was collected every 15 minutes 1 hour before (0800) and 2 hours after treatment (0900-1100). The treatment was administered in a randomized fashion and consisted of naloxone 1 or 4 mg or placebo, and blood was assayed for luteinizing hormone (LH). Baseline estradiol, progesterone, and prolactin were measured at 0800 and 0900 hours. RESULTS: There was a significant increase in LH area under the curve and mean LH in response to naloxone in the midluteal phase in the control (P < .001). The PMS subjects did not display a significant increase in LH concentration in response to naloxone in the midluteal phase. There were no significant LH responses to naloxone in either group in the late luteal phase. There were no significant differences in estradiol, progesterone, or prolactin concentrations or estrogen to progesterone ratios between groups. CONCLUSION: Control women have an enhanced central opioid tone during the midluteal phase that diminishes and becomes minimal in the late luteal phase of the menstrual cycle. In contrast, women with PMS have a loss of central opioid tone during the midluteal phase as indicated by the loss of LH response to naloxone. This attenuated central opioid tone in women with PMS as compared with asymptomatic control women may play a role in the pathophysiology of PMS.

Menstrual patterns in women with congenital heart disease.

To examine the extent to which congenital heart disease (CHD) influences ovarian function, 98 women (mean age 32.7 years) were asked to complete a mailed questionnaire regarding their menstrual patterns. Patients were divided into acyanotic (60%) and cyanotic (38.8%) groups. Cycle lengths, duration of menstrual cycle, regularity of menses, amount of flow, and breakthrough bleeding were compared in these two groups and against age-matched controls. The mean age of menarche for the sample (13.4 years) was significantly different (p < 0.004) when compared to their controls (12.5 years). With the exception of breakthrough bleeding, statistical differences were not found between the study population and the controls. When the menstrual histories of cyanotic women were compared with those of acyanotic women, differences were found for all categories of menstrual patterns with the exception of the amount of menstrual flow. Menstrual patterns of cyanotic women compared to controls were found to be significantly different for all categories with the exception of amount of flow. In general, women with CHD have menstrual patterns similar to those in the general population.

Menstrual cycle and social behavior in vervet monkeys.

We assessed the relationship between social behavior and the menstrual cycle in 11 adult female vervet monkeys (Cercopithecus aethiops sabaeus) living in an established, stable social group. The findings indicated that fluctuations in ovarian steroids are accompanied by behavioral changes in vervet monkeys. A significant increase in aggressive action, avoidance of social overtures, and retreats from threat occurred during the late luteal phase. However, the social environment can greatly affect behavior independent of the phase of the menstrual cycle. The 10 nondominant (or subordinate) individuals not only exhibited behavioral changes across their own menstrual cycles, but also were responsive to the dominant female's cycle. During the dominant female's late luteal phase, subordinate females significantly increased aggression and decreased social activity. Some of behavioral patterns in female vervet monkeys are therefore relatively independent of direct hormonal modulation and support the contention of the dominant female as the driving force for behavioral changes related to aggression and social interaction. The differential effect of hormones and social status and other environmental factors on behavior has not been critically evaluated in human studies of the premenstrual syndrome. The present study suggests that it is important to assess which behavioral patterns in women are hormonally mediated and which are dependent on the environment.

Gastroenterologic causes of chronic pelvic pain.

A large proportion of women with chronic pelvic pain can be found to have gastrointestinal disorders, either pathologic or functional. The location of referred pain from the gastrointestinal tract overlaps that of the reproductive organs. An awareness of the differential diagnosis, a knowledge of the common presentations of gastrointestinal disorders, a thorough history that includes an appropriate discussion of gastrointestinal symptoms, and a relevant examination will ensure that gastrointestinal diagnoses are not overlooked.

Tryptophan and neutral amino acids in premenstrual syndrome.

An abnormality of the serotonin system may play a role in the genesis of the symptoms of premenstrual syndrome, especially those related to mood and appetite. Whole blood and platelet uptake of serotonin are decreased during the luteal phase in women with premenstrual syndrome. The ratio of L-tryptophan (the amino acid precursor of serotonin) to the sum of the other neutral amino acids that compete for the same protein carrier cerebral uptake mechanism has been suggested to reflect central L-tryptophan levels and resultant serotonin levels in the brain. We evaluated the ratio of plasma L-tryptophan to the sum of five competing neutral amino acids in women with premenstrual syndrome and in controls. There were no significant differences between groups or across time, suggesting that it is unlikely that the aberrations of the serotonergic system in women with premenstrual syndrome are due to saturation of the tryptophan-carrying protein.

Unwanted sexual experiences among middle and high school youth.

Of the 1197 middle and high schoo students who participated anonymously in a health survey, 15% reported they had had a past unwanted sexual experience. Females were more likely than males and older students more likely than younger students to have had such experiences, which were categorized into six types: force/rape, child abuse, influence of drugs/alcohol, partner pressure, regret, and peer pressure. Male students tended to report peer pressure and regret more often than females, who tended to report forced situations and child abuse. The genders were similar, however, regarding partner pressure and the influence of drugs and alcohol. Students who reported having had an unwanted sexual experience were more likely to report current risk taking behaviors, school problems, and health problems that those who had not had such experiences. Students who had been physically forced were less likely to be currently sexually active and scored lower on a measure of current substance use than those who were not forced.

Differences in knowledge of and risk factors for AIDS between Hispanic and non-Hispanic women attending an urban family planning clinic.

Risk factors for AIDS, contraceptive use, seroprevalence of HIV, and level of knowledge before and after an AIDS education session were assessed for 657 clients attending a family planning clinic in Los Angeles, USA. History of a partner who was bisexual, an intravenous drug user, or a blood transfusion recipient were the most common risk factors. Spanish speakers reported fewer traditional risk factors than English speakers. They were also less likely to report a history of drug or alcohol use or sexually transmitted diseases, and to have had fewer sexual partners. Less than one-third of the women identified as being at risk of exposure were using condoms. None of 351 consecutive patients tested for HIV antibodies was positive. English speakers scored higher on both pre- and post-tests of knowledge about AIDS. Cultural factors may lower the personal risk of HIV exposure for Spanish-speaking women, but lack of knowledge about AIDS and partner behavior may increase risk.

History of physical and sexual abuse in women with chronic pelvic pain.

The history of physical and sexual abuse in childhood and adulthood was assessed in 31 women with chronic pelvic pain, 142 women with chronic pain in other locations, and 32 controls. Thirty-nine percent of patients with chronic pelvic pain had been physically abused in childhood. This percentage was significantly greater than that observed in other chronic-pain patients (18.4%) or controls (9.4%), though the prevalence of childhood sexual abuse did not differ among the groups (19.4, 16.3, and 12.5%, respectively). Abuse in adulthood was less common and was not significantly more likely to have occurred in patients with chronic pelvic pain than in other chronic-pain patients or controls. These data suggest that pelvic pain is unlikely to be specifically and psychodynamically related to sexual abuse but that the pernicious nature of abuse, whether physical or sexual, may promote the chronicity of painful conditions.

Mood and cognitive style in premenstrual syndrome.

Women with premenstrual syndrome (PMS) report symptoms that resemble those of affective disorder. In depression, there is an alteration in cognitive processing and performance such that dysphoric material is retrieved more readily and the ability to concentrate and sustain attention and motivation is impaired. To determine whether PMS leads to changes in information processing similar to those accompanying depression, ten subjects with PMS and nine controls were subjected to psychological testing, selective and incidental recall tests, and measures of cognitive performance during the follicular and luteal phases of the menstrual cycle. Women with PMS failed to show the characteristic cognitive changes that usually accompany depression. Despite substantial symptomatology, there were no significant differences in cognitive functioning between PMS subjects and controls.

Platelet monoamine oxidase B activity in women with premenstrual syndrome.

Several lines of evidence suggest a strong association between premenstrual syndrome and affective disorder. Similar psychological symptoms, behavioral manifestations, and biochemical etiologies have been reported. We attempted to evaluate the biologic interconnection between premenstrual syndrome and psychiatric disorder by investigating the platelet enzyme, monoamine oxidase B. The activity of this enzyme has been noted to be decreased in affective disorder, alcoholism, and psychiatric vulnerability. Platelet monoamine oxidase B activity, estradiol, and progesterone were assessed throughout one menstrual cycle in 13 women with premenstrual syndrome and 19 control subjects. No significant differences were noted between groups using these parameters. The study indicates that well-screened subjects with premenstrual syndrome are, as evidenced by the parameter of monoamine oxidase B, biochemically similar to normal control subjects.

Non-availability of the IUD and contraceptive choice.

The Copper 7 and Lippes Loop IUD are no longer distributed in the United States, and the cost of the Progestasert precludes usage in many family planning clinics. The impact of the loss of this widely used contraceptive method was assessed in a pilot study at the UCLA Family Planning Clinic. The clients who would have selected an IUD at the time of their clinic visit between March and December of 1986 instead chose oral contraceptive pills (55%) or barrier methods (45%) but their level of dissatisfaction with the methods they received was significantly greater than that of all other contraceptors, and this led to their subsequent selection of another method which, in the majority (66%), was of lower efficacy than the IUD. There were two unplanned conceptions amongst twenty women who would have chosen an IUD, both due to non-compliance with oral contraceptive pills; and at the time of survey in March 1987, no clients had opted for sterilization. Women who no longer have their choice of the IUD represent a high risk for contraceptive dissatisfaction and failure, but have not made precipitous decisions to undergo permanent sterilization.

PIP: The Copper 7 and Lippes Loop IUD are no longer distributed in the US, and the cost of the Progestasert precludes usage in many family planning clinics. The impact of the loss of this widely used contraceptive method was assessed in a pilot study at the UCLA Family Planning Clinic. The clients who would have selected an IUD at the time of their clinic visit between March and December of 1986 instead chose oral contraceptive pills (55%) or barrier methods (45%) but their level of dissatisfaction with the methods they received was significantly greater than that of all other contraceptors, and this led to their subsequent selection of another method which, in the majority (66%), was of lower efficacy than the IUD. There were 2 unplanned conceptions amongst 20 women who would have chosen an IUD, both due to non-compliance with oral contraceptive pills; and at the time of survey in March 1987, no clients had opted for sterilization. Women who no longer have their choice of the IUD represent a high risk for contraceptive dissatisfaction and failure, but have not made precipitous decisions to undergo permanent sterilization.

Whole-blood serotonin in premenstrual syndrome.

Whole-blood serotonin levels in 14 subjects with well documented premenstrual syndrome and 13 age-matched controls were compared. Serotonin levels of premenstrual syndrome subjects were significantly lower during the last ten days of the menstrual cycle. No significant differences were noted in levels of serum estradiol and progesterone. Decreased serotonin is known to be associated with depression in humans, and nonhuman primates have exhibited abnormal behavioral profiles when given serotonin antagonists. The present observation suggests that the physiologic basis of premenstrual syndrome involves an alteration in serotonin metabolism.