Sarah L. Berga

Melatonin suppression in bipolar and unipolar mood disorders

Nocturnal melatonin suppression to 500 lux light was studied during an acute episode of illness in 8 patients with bipolar disorder, 7 patients with unipolar depression, and 15 age-, sex-, and season-matched normal controls. Unipolar patients did not differ from controls in melatonin suppression. In contrast to previous studies, controls showed greater melatonin suppression than bipolar patients. Baseline melatonin concentration, however, was significantly lower in the bipolar group compared to the unipolar and control groups.

Circadian Pattern of Plasma Melatonin Concentrations during Four Phases of the Human Menstrual Cycle

The role of melatonin in human reproductive physiology remains obscure. Previous investigations of the nocturnal melatonin secretory pattern during the human menstrual cycle have yielded conflicting results and have been limited by incomplete characterization of the pertinent features of the circadian pattern such as magnitude, duration, or circadian position of the nocturnal increase, by incomplete assessments of ovarian secretion and menstrual cycle phase, or by both. In the present study, the circadian melatonin profile was characterized by obtaining plasma samples at hourly intervals from 10.00 to 17.00 h and at half-hourly intervals from 17.00 to 10.00 h in 10 women during four prospectively estimated menstrual phases: early follicular, late follicular, midluteal, and late luteal. Menstrual phases and ovarian function were confirmed by obtaining daily serum samples for LH, FSH, estradiol, and progesterone during the entire menstrual cycle. Eight women had ovulatory cycles with luteal lengths of greater than 11 days and with determinations of the circadian melatonin pattern during each menstrual phase. Despite gonadal steroid excursions characteristic of ovulatory cycles, consistent variations in plasma melatonin patterns by menstrual phase were not found. Daytime levels were at or below 43 pmol/l in all women and all but 2 women displayed prominent nocturnal elevations. While changes in the circadian pattern of melatonin secretion immediately preceding the LH surge cannot be excluded, the lack of consistent variation by menstrual cycle phase and the absence of clear circadian variation found in 2 women suggests that the secretory profile of melatonin is unaltered by fluctuations in gonadal steroids and that melatonin secretion may not be necessary for menstrual cyclicity to occur.

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome * †

OBJECTIVE To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN Prospective controlled trial. PATIENTS, PARTICIPANTS Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.

Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty

Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9:00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropin-releasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations.

Light suppression of melatonin in unipolar depressed patients

The effects of nocturnal light (500 lux) exposure on plasma melatonin were studied in seven men suffering from unipolar depression and in seven healthy men. Both groups showed significant declines in plasma melatonin concentrations during 1 hours light exposure. Differential group declines were not detected.