Search

Objective To compare the effects of oral micronized E 2 with transdermal E 2 on endometrial receptivity in women undergoing oocyte donation. Design Prospective, randomized, crossover trial. Serum E 2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and β -3-integrin expression. Setting University-based donor oocyte program. Patients Twenty-seven patients presenting for donor oocytes. Main Outcome Measures Endometrial histology and β -3-integrin expression. Results The endometrial glandular histology in women given oral micronized E 2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E 2 . Seventy percent of women given oral E 2 displayed a lag ≥4 days whereas 29.6% given transdermal E 2 displayed a similar lag. Serum E 2 levels were 1,194±108.8pg/mL (mean±SEM; conversion factor to SI unit, 3.671) in women on oral micronized E 2 and 117.4±14.0pg/mL in those on transdermal E 2 . Conclusion The supraphysiologic serum E 2 levels associated with oral micronized E 2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.

Insulin resistance and dyslipidemia have been described in women with polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism and oligomenorrhea. Although oral contraceptives (OC) are often instituted to regulate menses and suppress HA in women with PCOS, their use has been postulated to cause a deterioration in insulin sensitivity and to adversely affect circulating lipids. To investigate these effects, 9 women with PCOS and 10 age- and weight-matched control women were studied before and during the third month of therapy with a low-dose norethindrone-containing triphasic combination OC using the hyperglycemic clamp technique. At baseline, the PCOS group had higher androgen, triglyceride, and glycosylated hemoglobin concentrations, with a greater insulin response to oral glucose and a lower insulin sensitivity index (ISI) than controls. During OC therapy, a reduction in ISI was observed in both groups, whereas an increase in triglycerides was observed only in controls, removing any observed difference between the two groups in ISI or lipids. In women with PCOS, an increase in insulin concentrations during hyperglycemia accounted for the decline in ISI (P = 0.026), whereas in control women the decrease in ISI was attributable to a decrease in glucose disposal (P = 0.004). In conclusion, PCOS is characterized by insulin resistance in the untreated state. Short-term therapy with a triphasic OC results in a further decline in ISI in women with PCOS, without inducing additional adverse effects on lipids. A more pronounced decline in ISI together with an elevation in triglyceride levels occurs in normal women with OCs. The mechanisms leading to this decrease in ISI are different for each group.

We evaluated if the effects of acute stress on immune parameters were apparent in only the women who showed concomitant and substantial sympathetic nervous system activation and after statistical adjustment for changes in plasma volume. Nineteen women in the follicular stage of their menstrual cycles were assessed for immunological responsiveness to a series of three 3-minute psychological tasks, which reliably elicit cardiovascular and neuroendocrine stress responses. Women were classified as high or low sympathetic reactors based on their cardiovascular and neuroendocrine responses to one of the three tasks, a public speaking task. The stress-induced decreases in CD4+ percentage and increases in natural killer cell number and cytolytic activity were only apparent among the high reactors. Further analysis adjusting for alterations in plasma volume changes showed that the increase in NK cell number remained. Stress-induced proliferative responses to pokeweed mitogen and phytohemagglutinin were not more apparent among high reactors. These results are consistent with the hypothesis that the sympathetic nervous system plays a direct role in modulating the short term response to stress of some indices of the immune system in women.

Glucose clamp techniques are established methods for assessment of insulin sensitivity and secretion. The minimal model technique (MMT) has been proposed as an alternative approach to the hyperinsulinemic-euglycemic clamp technique for determination of an insulin sensitivity index (ISI), but has not been directly compared with the hyperglycemic clamp for measurement of ISI or insulin secretion. To address this issue, the present study was undertaken to compare determinations of ISI and the acute insulin response to glucose (AIRg) obtained using the MMT with similar measures obtained from a hyperglycemic clamp. Measures for ISI and AIRg obtained from MMT analysis of a tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIGT) were compared with similar measures obtained from a 3-hour hyperglycemic clamp performed at a plasma glucose level of 10 mmol/L (180 mg/dL). Paired comparisons were performed in 14 women with normal glucose tolerance. Significant positive correlation coefficients were obtained for both ISI (r = .88, P < .001) and AIRg (r = .75, P < .005) between the MMT and clamp studies. We conclude that indices for ISI and AIRg obtained with the MMT are highly correlated with those obtained using the hyperglycemic clamp. The MMT is a valid alternative to the hyperglycemic clamp for assessing insulin sensitivity and AIRg.

Abstract The goal of the study was to compare cardiovascular heart disease risk factors in women with polycystic ovary syndrome (PCOS) and matched control subjects. Women with PCOS have risk factors, including anovulation, hyperandrogenism, and insulin resistance, that suggest a male coronary heart disease risk-factor profile. A total of 206 women with PCOS were recruited by using records from a large reproductive endocrinology practice. A clinical diagnosis of PCOS was made if there was a history of chronic anovulation in association with either clinical evidence of androgen excess (hirsutism) or if total testosterone level was >2 nm/L or the luteinizing hormone/follicle-stimulating hormone ratio was greater than 2. The overall response rate for cases was 76%. A control population was obtained by using a combination of area voters’ registration tapes and directories of households. A control subject was matched to each case subject by age±5 years, race, and neighborhood. The response rate for recruitment of the first or second eligible control subject was 83.6%. The average age at initial interview was 35.9±7.4 years for case and 37.2±7.8 years for control subjects. Women with PCOS had significantly increased cardiovascular disease risk factors compared with control women. These included increases in body mass index, insulin, and triglyceride levels ( P 2 levels ( P P 2 , LDL cholesterol, and triglycerides were still significant between case and control subjects. These risk factors were especially elevated in PCOS women in the early premenopausal years compared with control women, indicating that women with PCOS should be monitored for early detection and considered for appropriate clinical interventions.

Background Rupture of the fetal membranes is a common harbinger of imminent labor and delivery. Telomere shortening is a surrogate for oxidative stress (OS) and senescence. Fetal leukocyte and placental membrane DNA telomere lengths were evaluated to determine their association with preterm prelabor rupture of the membranes (pPROM) or spontaneous preterm births with intact membranes (PTB), compared to term birth. Methods Telomere lengths were quantified in cord blood leukocytes (n = 133) from three major groups: 1) pPROM (n = 28), 2) PTB (n = 69) and 3) uncomplicated full term births (controls, n = 35), using real-time quantitative PCR. Placental membrane specimens (n = 18) were used to correlate fetal leukocyte and placental telomere lengths. Telomere length differences among the groups were analyzed by ANOVA. Pearson correlation coefficients determined relationships between leukocyte and placental membrane telomere lengths. Results In pregnancies with intact membranes, fetal leukocyte telomere length was inversely proportional to gestational age. The mean telomere length decreased as gestation progressed, with the shortest at term. pPROM had telomere lengths (9962±3124 bp) that were significantly shorter than gestational age-matched PTB (11546±4348 bp, p = 0.04), but comparable to term births (9011±2497 bp, p = 0.31). Secondary analyses revealed no effects of race (African American vs. Caucasian) or intraamniotic infection on telomere length. A strong Pearson's correlation was noted between fetal leukocyte and placental membrane telomere lengths (ρ = 0.77; p

It is not understood why disturbed menstrual function occurs in as many as 50% of women with bulimia nervosa who are at normal weight. The authors measured luteinizing hormone (LH), estradiol, and progesterone in 13 women with bulimia nervosa who were at normal weight and six normal comparison subjects. They found that the women with bulimia nervosa were likely to have abnormal 24-hour luteinizing hormone (LH) secretion if their current weight was less than 85% of their past high weight.

Background Cardiovascular disease remains the primary cause of death worldwide. In the US, deaths due to cardiovascular disease for women exceed those of men. While cultural and psychosocial factors such as education, economic status, marital status and access to healthcare contribute to sex differences in adverse outcomes, physiological and molecular bases of differences between women and men that contribute to development of cardiovascular disease and response to therapy remain underexplored. Methods This article describes concepts, methods and procedures to assist in the design of animal and tissue/cell based studies of sex differences in cardiovascular structure, function and models of disease. Results To address knowledge gaps, study designs must incorporate appropriate experimental material including species/strain characteristics, sex and hormonal status. Determining whether a sex difference exists in a trait must take into account the reproductive status and history of the animal including those used for tissue (cell) harvest, such as the presence of gonadal steroids at the time of testing, during development or number of pregnancies. When selecting the type of experimental animal, additional consideration should be given to diet requirements (soy or plant based influencing consumption of phytoestrogen), lifespan, frequency of estrous cycle in females, and ability to investigate developmental or environmental components of disease modulation. Stress imposed by disruption of sleep/wake cycles, patterns of social interaction (or degree of social isolation), or handling may influence adrenal hormones that interact with pathways activated by the sex steroid hormones. Care must be given to selection of hormonal treatment and route of administration. Conclusions Accounting for sex in the design and interpretation of studies including pharmacological effects of drugs is essential to increase the foundation of basic knowledge upon which to build translational approaches to prevent, diagnose and treat cardiovascular diseases in humans.

Women with hyperandrogenic anovulation (HAA) have increased circulating levels of LH relative to those of FSH. The cause of this disturbance in gonadotropin secretion is uncertain. Previous investigations have sought to determine if increased GnRH drive is responsible for the excessive LH concentrations. Because previous results have conflicted, we addressed this question by comparing the 24-h secretory patterns of alpha-subunit and LH in women with HAA (n = 9) to those in eumenorrheic women in the midfollicular phase (n = 9). The mean (+/- SEM) pulse frequency was increased in women with HAA compared to that in eumenorrheic women of comparable age and percent ideal body weight for both LH (23.0 +/- 0.7 pulses/24 h vs. 3 17.1 +/- 1.7; P = 0.002) and alpha-subunit (23.0 +/- 0.8 vs. 19.1 +/- 1.2; P = 0.02). LH and alpha-subunit, but not FSH, responses to a submaximal dose of exogenous GnRH were increased in HAA, as were basal LH and alpha-subunit levels (P0.01). The present observations provide evidence for increased GnRH drive, including pulse frequency, in HAA. Although the results confirm the presence of a disturbance in gonadotropin secretion and suggest that its proximate cause may be of hypothalamic origin, they do not exclude the possibility that other factors, perhaps of ovarian origin, play a role in the establishment and/or maintenance of the altered gonadotropin secretory patterns and the chronic anovulation characteristic of HAA.

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.

Dewan asserted 20 years ago that a bedside light could shorten and regularize the menstrual cycle among women with long and irregular menstrual patterns. To replicate this, seven volunteers slept with a 100-watt bulb by the bedside from days 13-17 of their menstrual cycles, while nine controls similarly used a dim red placebo (photographic safe light). Indeed, the 100-watt bulbs shortened menstrual cycles from a mean of 45.7 days to 33.1 days and reduced variability, but the placebo had no effect. These results suggest that light may have promise for treatment of infertility, for contraception, and for other endocrine interventions.

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.

Nature Neuroscience 9, 1362–1363 (2006); Published online 1 October 2006; corrected after print 23 January 2007 In the version of this article originally published, E.L. Moses-Kolko and S.L. Berga were omitted from the author list. In addition, the affiliation for C.C. Meltzer was incomplete. The correct author list and affiliations, along with a revised author contribution statement, are given below.

(1998). Hypothalamic Pituitary Gonadal Axis: Stress-Induced Gonadal Compromise. Journal of Musculoskeletal Pain: Vol. 6, No. 3, pp. 61-62.

receptor bind-ing potential in specific brain regions of interest. However, wealert readers to our more recent publication (2), in which ouroriginal image data were analyzed voxel by voxel using statis-tical parametric mapping, a technique similar to that appliedby Dr. Kugaya et al. Consistent with the work of Dr. Kugaya etal., this approach showed that administration of estradiolalone increased 5-HT

• The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight ageand menstrual cycle phase—matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal, and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome.

Women with functional hypothalamic amenorrhea display multiple neuroendocrine aberrations suggestive of altered central neurotransmission. The role of antecedent stress as an explanation for both the neurochemical changes and the dysfunctional behavior of these women is examined by utilizing concepts provided by the animal model of inescapable shock and the human condition of post traumatic stress disorder.

✓ The proper treatment of multiple and incidental aneurysms remains controversial because the long-term result of different modes of management is unclear. This report evaluates the long-term outcome (follow-up period averaged 7.7 years) in 182 patients with multiple aneurysms who suffered a subarachnoid hemorrhage (SAH) to document the incidence of late bleeding. Of the 182 patients, 132 were treated by bed rest and 50 by surgery (craniotomy) directed at only the ruptured aneurysm. Seventy of the patients with bed rest were alive after 6 months. Twenty-one of these conservatively treated patients (30%) suffered a late hemorrhage, which is equal to the previously reported average yearly rebleed rate (3%) with a single aneurysm of the anterior circulation. There was no evidence that a previously intact aneurysm had ruptured in SAH patients treated with bed rest, indicating that late hemorrhage was due to rerupture from the original aneurysm. Patients who were hypertensive and who had a large aneurysm had an increased risk of late rehemorrhage. A linear discriminant analysis was developed to predict late rebleeding. The fate of intact aneurysms was evaluated by following patients with multiple aneurysms treated by craniotomy directed only at the ruptured aneurysm. Of the 50 craniotomy patients, 38 were alive after 6 months. In this group, the minimal risk of rupture of an intact aneurysm is approximately 1% per year. The presence of hypertension increased the risk of late hemorrhage. In conclusion, patients with multiple untreated aneurysms managed by bed rest have a late rehemorrhage rate equal to that observed in patients with a single cerebral aneurysm; the data indicate that rupture of intact aneurysms is not insignificant.

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 hour's light exposure. Differential group declines were not detected.

Hypercortisolism was found in patients with functional hypothalamic amenorrhea (HA) in preliminary short term studies conducted during the morning hours (0800-1100 h). This observation prompted us to characterize the circadian and pulsatile patterns of serum cortisol and LH levels at 15-min intervals for 24 h in 10 women with functional HA and in 7 normal women during the early follicular phase of their cycles. The mean integrated 24-h serum cortisol levels (area under the curve) were significantly (P less than 0.01) higher in the HA patients than in normal women. The mean cortisol levels in the HA patients were elevated (P less than 0.005) compared to those in the normal women during the daytime hours (0800-1600 h), but not during the evening (1600-2400 h) and sleeping hours (2400-0800 h). This selective hypercortisolism during the waking period of the day was almost entirely related to increased duration and amplitude of secretory episodes (peak area) rather than a change in pulse frequency. The serum cortisol increments in response to a noon meal that occurred in normal women were markedly impaired (P less than 0.01) in the HA patients. Compared with that in the normal women, mean LH pulse frequency was reduced by 30% in the HA patients. The 24-h mean LH levels and mean LH pulse amplitude were not significantly different from those in the normal women. However, among the HA patients there were marked individual differences in LH pulse frequency and amplitude, with prolonged interpulse quiescent periods, indicative of dysfunction of the hypothalamic GnRH pulse generator. We conclude that neuroendocrine activation of the ACTH-adrenal axis and inhibition of the GnRH pulse generator in women are associated with HA. Further, spontaneous resumption of normal cyclicity occurred in the majority (8 of 10) of the HA patients with no medical treatment, suggesting that this syndrome is a reversible hypothalamic disorder of a functional nature.

To further elucidate the neuroendocrine regulation of anterior pituitary function in women with functional hypothalamic amenorrhea (FHA), we measured serum LH, FSH, cortisol, GH, PRL, TSH concentrations simultaneously at frequent intervals for 24 h in 10 women with FHA and in 10 normal women in the early follicular phase (NC). Using the same data, we separately analyzed the cortisol-PRL responses to meals in these women. In addition, the pituitary responses to the simultaneous administration of GnRH, CRH, GHRH, and TRH were assessed in 6 FHA and 6 normal women. The 24-h secretory pattern of each hormone except TSH was altered in the women with FHA. Compared to normal women, the women with FHA had a 53% reduction in LH pulse frequency (P less than 0.0001) and an increase in the mean LH interpulse interval (P less than 0.01); LH pulse amplitude was similar. The 24-h integrated LH and FSH concentrations were reduced 30% (P = 0.01) and 19% (P less than 0.05), respectively. The mean cortisol pulse frequency, amplitude, interpulse interval, and duration were similar in the two groups, but integrated 24-h cortisol secretion was 17% higher in the women with FHA (P less than 0.05). This increase was greatest from 0800-1600 h, but also was present from 2400-0800 h. Cortisol levels were similar in the two groups from 1600-2400 h, resulting in an amplified circadian excursion. In contrast, the 24-h serum PRL levels were markedly lower at all times (P less than 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P less than 0.05), and serum GH levels were increased at night in the women with FHA (P less than 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P less than 0.05) and T4 (P less than 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P less than 0.01) and dinner (P less than 0.05) and those of serum PRL to lunch (P less than 0.05) and dinner (P = 0.08) were blunted in the women with FHA. Pituitary hormone increments in response to the simultaneous iv administration of GnRH, CRH, GHRH, and TRH were similar in the two groups, except for a blunted PRL response to TRH in the women with FHA (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Agonist analogs of GnRH were used to effect a "medical castration" in 14 patients with uterine fibroids, presenting with either an enlarged uterus, recurrent menometrorrhagia, and/or infertility. This study confirms prior reports of a reduction in uterine size and cessation of menometrorrhagia in patients with fibroids following treatment with GnRHa. Of interest, however, was the successful use of GnRHa as either the sole treatment for uterine fibroid-associated infertility, or as a preoperative adjunct in infertility patients scheduled for myomectomy. Three of the five infertility patients in this study achieved intrauterine pregnancies. Further study of the role of GnRHa treatment in infertility patients with uterine fibroids appears warranted.

Plasma melatonin levels were determined by a sensitive RIA at 30 min intervals for 24h in 7 women with functional hypothalamic amenorrhea (HA) and in 7 age and season matched normal cycling women in the early follicular phase (NC). While daytime melatonin concentrations were nondetectable in both groups, the integrated nocturnal levels were 3-fold greater in HA (244 +/- 58 (SE) vs 74 +/- 32 pmol-min/Lx10(3), p less than 0.005). This melatonin increase in HA was due to an elevated peak amplitude (p less than 0.01) and extended duration (p less than 0.05). The latter was mostly due to a significant delay in the offset time of the amplified nocturnal melatonin secretion.

Women with polycystic ovary syndrome (PCO) display disordered patterns of LH pulsatility and may have an impairment of opioidergic regulation of GnRH-LH. In order to ascertain if these patterns reflect an inherent hypothalamic abnormality or a functional state consequent to the acyclicity of sex steroids, LH pulsatility and gonadotrophin responses to naloxone were examined in six PCO women before and after treatment with incremental daily doses of a progestogen, medroxyprogesterone acetate (MPA), for 10 days to determine (i) if progestogen treatment would alter the LH pulse pattern to resemble that of the luteal phase; and (ii) if the conversion to a luteal phase LH pulse pattern by MPA would involve the induction of opioidergic regulation. LH pulsatility and FSH levels were determined by blood sampling at 10 min intervals for 8 h before and after MPA treatment during a saline infusion on the control day and during a naloxone infusion (1.6 mg/h) on the following day. Basal levels of oestradiol, oestrone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate were measured before and after MPA. All six PCO women responded to MPA administration with a significant reduction in LH pulse frequency (P less than 0.005), an increase in LH pulse amplitude (P less than 0.0025), and an increase in LH pulse duration (P less than 0.025), without changes in mean LH, mean FSH, androgen, or oestrogen levels. Thus, a luteal phase LH pulse pattern was induced by MPA. Naloxone reversed the MPA-induced changes in LH pulsatility, indicating that these responses involved the induction of central opioidergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)To determine whether the disordered patterns of luteinizing hormone (LH) pulsatility and impaired opioidergic regulation of gonadotropin- releasing hormone (GnRH)-LH observed in women with polycystic ovarian syndrome reflect an inherent hypothalamic abnormality or a functional state related to the acyclycity of sex steroids, medroxyprogesterone acetate was administered to 6 women with this syndrome. It was hypothesized that if the apparent lack in women with polycystic ovarian syndrome of opiodergic regulation of GnRH-LH release was in fact secondary to an inherent hypothalamic defect, then the administration of this progestogen would fail to produce opiodergic regulation of GnRH-LH. Medroxyprogesterone acetate was given orally to the 6 study subjects over a 10-day period in an incremental dosage to mimic the luteal phase. LH pulsatility and follicle-stimulating hormone (FSH) levels were measured at 10 minute intervals during the 8 hours before and after treatment and infusions of saline or naloxone were given. All 6 subjects showed significant changes in LH pulsatile activities after steroid administration, specifically a slowing of LH pulse frequency and an increase in pulse amplitude and duration. Naloxone infusion reversed these progestogen-associated changes. There were no changes in mean LH, mean FSH, androgen, or estrogen levels, however, suggesting that a luteal phase LH pulse pattern was produced. Since naloxone reversed the changes in LH pulsatility induced by medroxyprogesterone acetate, it can be concluded that these responses involved the induction of central opiodergic activity secondary to ovarian acyclycity and progesterone deficiency, not a primary hypothalamic defect.

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.

Six women with late luteal phase dysphoric disorder had a significant reduction in depression ratings after treatment with evening, but not morning, bright light. Bright light may offer an alternative to the pharmacologic treatment of premenstrual mood disorders.

Background The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography. Results 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low. Conclusions Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.