Effect of Zinc Supplementation on Physical and Psychological Symptoms, Biomarkers of Inflammation, Oxidative Stress, and Brain-Derived Neurotrophic Factor in Young Women with Premenstrual Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial.

Zinc is known to have multiple beneficial effects including anti-inflammatory and antioxidant and anti-depressant actions. Data on the effects of zinc supplementation on biomarkers of inflammation, oxidative stress, and antidepressant-like effect among young women with premenstrual syndrome (PMS) are scarce. This study was a randomized, double-blind, placebo-controlled trial. Sixty women (18-30 years) with premenstrual syndrome diagnosed according to 30-item questionnaire were randomly assigned to receive either 30-mg zinc gluconate (group 1; n = 30) and/or placebo (group 2; n = 30) for 12 weeks. Premenstrual syndrome symptoms, total antioxidant capacity, high sensitivity reactive protein, and brain-derived neurotrophic factor were measured at study baseline and after 12-week intervention. After 12 weeks of intervention, PMS physical symptoms (P = 0.03) and psychological symptoms (P = 0.006) significantly decreased in zinc group compared to placebo group. We observed a significant increase in brain-derived neurotrophic factor (P = 0.01) and total antioxidant capacity (P Ë‚ 0.001) after 12 weeks of intervention with zinc compared to placebo. We failed to find any significant effect of zinc supplementation on high sensitivity reactive protein. Overall, zinc supplementation for 12 weeks among women with premenstrual syndrome had beneficial effects on physical and psychological symptoms of premenstrual syndrome, total antioxidant capacity, and brain-derived neurotrophic factor.

Vitamin D Supplementation for Premenstrual Syndrome-Related inflammation and antioxidant markers in students with vitamin D deficient: a randomized clinical trial.

Premenstrual syndrome (PMS) is a common disorder in the reproductive age that negatively significant impacts on women's quality of life. This randomized clinical trial study was undertaken to investigate the effect of vitamin D supplementation on inflammatory and antioxidant markers in 44 vitamin D deficient (25(OH)D < 20 ng/mL) students with PMS. Participants received either 50,000 IU vitamin D3 or a placebo pearl fortnightly for 4 months. At the baseline and in the last 2 months of intervention, participants were asked to complete the PMS Daily Symptoms Rating form along with taking the pearls and their blood samples were collected to assess serum levels of 25(OH)D3, Interleukin10 and 12 (IL-10, IL-12) and total antioxidant capacity (TAC). In vitamin D group, serum levels of IL-10 and IL-12 significantly decreased while TAC significantly increased post-intervention. There were significant differences regarding serum IL-12 and TAC levels between the two groups. Mean score of the total PMS symptoms showed significant improvement in 25(OH)D. Vitamin D supplementation seems to be an effective strategy to improve inflammation and antioxidant markers in vitamin D deficient women with PMS. This clinical trial was registered at Iranian Registry of Clinical Trials on 20/06/2018 (IRCT20180525039822N1).

Menstrual disorders and premenstrual symptoms in adolescents: prevalence and relationship to serum calcium and vitamin D concentrations.

There have been several studies evaluating the association between vitamin and mineral status and menstrual disturbance. In the present study, we aimed to assess the relationship between the menstrual bleeding pattern and premenstrual syndrome (PMS) symptoms with serum 25-hydroxyvitamin D, and calcium levels in adolescent girls. A cross-sectional study was carried out in 897 high school girls from northeastern Iran. The prevalence of hypocalcaemia, normal serum calcium and hypercalcaemia was 27.1, 59.8 and 13.1%, respectively. The menstrual flow of participants differed significantly between the calcium status groups (p = .005). There was no significant association between the symptoms of PMS, as assessed by the questionnaire and serum vitamin D status, or serum calcium concentrations, apart from the irritability. There appears to be an association between serum calcium, menstrual blood loss and irritability in adolescent girls. Impact statement What is already known on this subject? Several studies have evaluated the association of vitamin and mineral status with menstrual disturbance, although these relationships are not consistent, specifically among calcium and vitamin D levels with a menstrual bleeding pattern. What do the results of this study add? In the present study, we investigated the correlation of menstrual bleeding patterns and PMS with calcium and vitamin D levels in a large population in adolescent girls. We found that the level of calcium was associated with the level of menstrual blood loss and irritability. However, no significant association was observed between the menstrual bleeding pattern or the PMS symptoms with a vitamin D status. What are the implications of these findings for future clinical practise/research? Further studies are required to assess the value of a calcium adequate intake or a calcium supplementation for the amelioration of PMS and a better understanding the role of calcium in PMS.

Vitamin D Supplementation for Premenstrual Syndrome-Related Mood Disorders in Adolescents with Severe Hypovitaminosis D.

STUDY OBJECTIVE: Premenstrual syndrome (PMS) might become severe enough to interfere with normal interpersonal relationships. This study was planned to assess whether administration of vitamin D (200,000 IU at first, followed by 25,000 IU every 2 weeks) for a 4-month period might lessen the appearance and the intensity of mood disorders associated with PMS in young girls with severe hypovitaminosis D. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: One hundred fifty-eight young girls (15-21 years old) with PMS-related severe symptoms of the emotional and cognitive domains and low serum 25-hydroxycholecalciferol (25-OH-D) levels (≤10 ng/mL) were randomly assigned to two treatment groups and treated for 4 months with vitamin D (group 1; n = 80) or placebo (group 2; n = 78). Clinical and hormonal effects were compared between the two groups. RESULTS: In patients from group 1, levels of vitamin D reached the normal range (35-60 ng/mL) after the first month and remained stable throughout the whole study. At the end of treatment, anxiety score decreased from 51 to 20 (P < .001 vs baseline); irritability score declined from 130 to 70 (P < .001 vs baseline). Crying easily and sadness decreased by a score of 41 and 51 to a score of 30 and 31, respectively (P < .001). For disturbed relationships, the score decreased from 150 to 70 (P < .001). Conversely, no appreciable changes were noted in symptom intensity from patients of group 2. The frequency of adverse events (nausea and constipation) was not different between participants of group 1 and group 2. CONCLUSION: On the basis of the present findings, vitamin D therapy can be proposed as a safe, effective, and convenient method for improving the quality of life in young women with severe hypovitaminosis D and concomitant mood disorders associated with PMS.

[Efficacy of acupuncture combined with auricular point sticking on the content of serum prostaglandin F2α, and plasma arginine vasopressin in patients with menstrual headache].

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with auricular point sticking for menstrual headache and to discuss its mechanism. METHODS: Eighty-five patients with menstrual headache were randomly divided into an observation group (43 cases) and a control group (42 cases). The observation group was treated with body acupuncture combined with auricular point sticking and the control group was treated with flunarizine hydrochloride capsules orally. The treatments of 3 menstrual cycles were required. The clinical efficacy was observed in the two groups. The content of serum prostaglandin F2α, (PGF2α) and plasma arginine vasopressin (AVP) in the menstrual periods of some patients randomly selected in the two groups was tested before and after treatment and was compared with that of 20 cases in a normal group. Results The total effective rate was 95.4% (41/43) in the observation group which was obviously superior to 81.0% (34/42) in the control group (P<0.01). Before treatment, the content of serum PGF2α and plasma AVP of patients in the two groups was higher than that in the normal group (all P<0.01). After treatment,the content of serum PGF2α and plasma AVP was lower than that before treatment in the two groups (P<0.01, P<0.05). The content of serum PGF2α in the observation group was decreased significantly compared with that in the control group (P<0.05) and returned to the level of the normal group. CONCLUSION: Body acupuncture combined with auricular point sticking achieves positive efficacy for menstrual headache and its mechanism could be related to regulating the abnormal levels of serum PGF2α and plasma AVP.

Effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women.

The objective of this study was to investigate the effect of aerobic exercise on premenstrual symptoms, haematological and hormonal parameters in young women. A total of 30 participants aged 16-20 years and complaining of premenstrual syndrome (PMS) were randomly assigned into two groups: a control group received vitamin B6 and Ca supplements once daily and a study group received the same medical treatment and participated in treadmill training three times per week for 3 months. A premenstrual syndrome questionnaire (MSQ), complete blood picture and hormone assays were performed for the assessment of all participants at the start and after the end of the treatment course. The study group showed a significant decrease in all post-treatment subscale symptoms, scores and total score. Haemoglobin, haematocrit, red cell count and platelet count were significantly increased, while mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and white blood cell count showed no significant differences. There was also a significant decrease in prolactin, oestradiol and progesterone levels. In conclusion, aerobic exercise increases haemoglobin, haematocrit, red cell count and platelet count, and decreases levels of prolactin, oestradiol and progesterone, resulting in improvement of fatigue, impaired concentration, confusion and most premenstrual symptoms.

The correlation between neurosteroids and neurotransmitters with liver yang rising and liver qi stagnation types of premenstrual syndrome.

BACKGROUND: To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS. METHODS: HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group). RESULTS: Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p < 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p < 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p < 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p < 0.05). CONCLUSION: The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.

Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a prospective cohort study.

BACKGROUND: Moderate to severe premenstrual syndrome (PMS) affects 8-20 percent of premenopausal women. Previous studies suggest that high dietary vitamin D intake may reduce risk. However, vitamin D status is influenced by both dietary vitamin D intake and sunlight exposure and the association of vitamin D status with PMS remains unclear. METHODS: We assessed the relation of plasma 25-hydroxyvitamin D (25OHD), total calcium and parathyroid hormone levels with risk of PMS and specific menstrual symptoms in a case-control study nested within the prospective Nurses' Health Study II. Cases were 401 women free from PMS at baseline who developed PMS during follow-up (1991-2005). Controls were women not experiencing PMS (1991-2005), matched 1:1 with cases on age and other factors. Timed luteal phase blood samples were collected between 1996 and 1999 from cases and controls. We used conditional logistic regression to model the relation of 25OHD levels with risk of PMS and individual menstrual symptoms. RESULTS: In analyses of all cases and controls, 25OHD levels were not associated with risk of PMS. However, results differed when the timing of blood collection vs. PMS diagnosis was considered. Among cases who had already been diagnosed with PMS at the time of blood collection (n = 279), 25OHD levels were positively associated with PMS, with each 10 nmol/L change in 25OHD associated with a 13% higher risk. Among cases who developed PMS after blood collection (n = 123), 25OHD levels were unrelated to risk of PMS overall, but inversely related to risk of specific menstrual symptoms. For example, each 10 nmol/L increase was associated with a significant 21% lower risk of breast tenderness (P = 0.02). Total calcium or parathyroid hormone levels were unrelated to PMS. CONCLUSIONS: 25OHD levels were not associated with overall risk of PMS. The positive association observed among women already experiencing PMS at the time of 25OHD measurement is likely due to confounding by indication related to use of dietary supplements to treat menstrual symptoms. Results from prospective analyses, which were less likely influenced by this bias, suggest that higher 25OHD levels may be inversely related to the development of specific menstrual symptoms.

[Analysis on content of serum monoamine neurotransmitters in macaques with anger-in-induced premenstrual syndrome and liver-qi depression syndrome].

OBJECTIVE: To observe the changes in content of monoamine neurotransmitters in the serum of rhesus macaques, and explore the role of serum monoamine neurotransmitters in premenstrual syndrome (PMS) and liver-qi depression induced by anger-in emotion. METHODS: Social level pressure was applied on 24 female macaques to induce the angry emotional reaction, and then nine of the low-status macaques with anger-in emotional reaction were screened out and were divided into anger-in emotion group, PMS and liver-qi depression group (model group) and Jingqianshu Granule group. Macaques in the last two groups were suffered extruding in a pack cage for inducing PMS liver-qi depression. After 5 d of extruding, experimental animals were evaluated according to the emotional evaluation scale, meanwhile, macaque serum of follicular phase and middle-late luteal phase was collected to analyze the content of serum norepinephrine, dopamine, and 5-hydroxytryptamine. RESULTS: Compared with the normal control group, the scores of depression of the model group and the anger-in emotion group evaluated with emotional evaluation scale were significantly increased (P<0.01, P<0.05); while the score of the model group was significantly higher than that of the anger-in emotion group (P<0.05), and it returned to normal after Jingqianshu Granule treatment. As compared to the normal control group, serum monoamine neurotransmitter levels of the model group and the anger-in emotion group were increased (P<0.05, P<0.01), and the serum monoamine neurotransmitter levels of the model group were significantly higher than those of the anger-in emotion group (P<0.05), while there was no significant difference when compared with the normal control group after the treatment. CONCLUSION: Anger-in emotion can induce liver-qi depression syndrome which is related to the changes in monoamine neurotransmitters.

[Study on preparation method of Yueanjian for treatmen of premenstrual syndrome].

OBJECTIVE: To establish the liver-depression and spleen-deficiency syndrome model in rats to screen the optimal extraction method of small compound Yueanjian on the basis of pharmacodynamic and chemical indicators. METHOD: The PMS liver-depression and spleen-deficiency syndrome model were established by the chronic restraint stress method and treatment with Yueanjian extracted by three methods: water-extraction, steam-distillation and alcohol-extraction. Behavioral performances and the contents of estradiol and progestin in serum were determined before and after the administration of the three extracts. The contents of salvianolic acid B in these three extracts were detected by HPLC. The optimal extraction method of Yueanjian was selected according to pharmacodynamic results. RESULT: The contents of estradiol and progestin in groups treated with steam distillations and alcoholic extraction were higher than the model group. In the open field test, the group treated with steam distillations showed much higher scores than the model group. HPLC showed that the content of salvianolic acid B extracted by steam-distillation was higher than the other two extracts. CONCLUSION: On the basis of pharmacodynamic and chemical results, the steam-distillation was proved to be best extraction method of Yueanjian.

[Correlation between neurotransmitters and neurosteroids and premenstrual syndrome patients of Gan-yang ascending syndrome and Gan-qi stagnation syndrome].

OBJECTIVE: To explore the pathogenesis of premenstrual syndrome (PMS), and the correlation between anger and depression and PMS of Gan-yang ascending syndrome (GYAS) and Gan-qi stagnation syndrome (GQSS) by detecting the neuro-reproductive hormones of PMS patients of GYAS and GOSS, thus providing theoretical reliance for diagnostic standards for clinical normative PMS. METHODS: Using techniques such as HPLC, HPLC-MC, ELISA, and radioimmunoassay (RIA), levels of serum sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin), plasma neurotransmitters (gamma-aminobutyric acid, beta-endorphin, glutamic acid, dopamine, 5-HT, adrenaline, and noradrenaline), neurosteroids (allopregnanolone, pregnenolone, and dehydroepiandrosterone) in the follicular phase and the luteal phase of PMS patients of GYAS (30 cases) and GQSS (30 cases) were detected, and compared with the healthy control group (30 cases). RESULTS: There was no statistical difference in either index of the follicular phase among the 3 groups. Compared with the healthy control group, the testosterone level in PMS patients of GYAS in the luteal phase showed increasing tendency (P > 0.05). The levels of dopamine and 5-HT of PMS patients of GYAS in the luteal phase were higher and the gamma-aminobutyric acid level was lower than those of the healthy control group (all P < 0.05). The levels of adrenaline and noradrenaline of PMS patients of GYAS and GQSS in the luteal phase were higher than those of the healthy control group (all P < 0.05). The levels of allopregnanolone and pregnenolone of PMS patients of GYAS and GQSS in the luteal phase were lower, and the dehydroepiandrosterone level was higher than those of the healthy control group (all P < 0.05). The ratios of dehydroepiandrosterone/allopregnanolone and dehydroepiandrosterone/pregnenolone of PMS patients of GYAS and GQSS in the luteal phase were higher than those of the healthy control group (P < 0.05). CONCLUSION: The decreased levels of pregnenolone and allopregnanolone, increased dehydroepiandrosterone levels, and increased ratios of dehydroepiandrosterone/allopregnanolone and dehydroepiandrosterone/pregnenolone might be one of biological factors for anger and depression in PMS patients of GYAS and GQSS.

Increased sensitivity to light-induced melatonin suppression in premenstrual dysphoric disorder.

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (-0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC subjects (p > .05).

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.

Dynamic changes in serum estradiol and progesterone levels in patients of premenstrual syndrome with adverse flow of liver-qi.

OBJECTIVE: To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome (PMS) and reveal partial microcosmic mechanisms of adverse flow of liver-qi. METHODS: Estradiol (E2) and progesterone (P) levels in serum were determined at different phases of menstrual cycle by radioimmunoassay. RESULTS: In the group of PMS with adverse flow of liver-qi, the secretive peak value of E2 and P at the follicular phase significantly decreased, and the secretive peak value at the luteal phase did not come into being. CONCLUSIONS: Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi. One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2 and P.

[Detection of monoamine transmitters in serum of macaque by high performance liquid chromatograghy with electrochemical detector].

OBJECTIVE: To develop an HPLC-ECD for the determination of monoamine transmitters in serum of macaque. METHOD: The analysis was carried out on a ZORBAX SB-C18 column (4.6 mm x 250 mm, 5 microm) eluted with a mobile phase of methanol-water (18:82) at a flow rate of 0.9 mL x min(-1). RESULT: The recoveries of NE, E, DA, 5-HT were 97.0%, 97.8%, 99.5%, 100.3%, RSD was 0.22%-0.93%, and the repeatability was good. CONCLUSION: The results prove that the method is simple, fast, accurate and can be used to determine simultaneously the concentration of monoamine transmitters in serum of macaque.

Calcium and vitamin D intake and risk of incident premenstrual syndrome.

BACKGROUND: Premenstrual syndrome (PMS) is one of the most common disorders of premenopausal women. Studies suggest that blood calcium and vitamin D levels are lower in women with PMS and that calcium supplementation may reduce symptom severity, but it is unknown whether these nutrients may prevent the initial development of PMS. METHODS: We conducted a case-control study nested within the prospective Nurses' Health Study II cohort. Participants were a subset of women aged 27 to 44 years and free from PMS at baseline in 1991, including 1057 women who developed PMS over 10 years of follow-up and 1968 women reporting no diagnosis of PMS and no or minimal menstrual symptoms. Intake of calcium and vitamin D was measured in 1991, 1995, and 1999 by a food frequency questionnaire. RESULTS: After adjustment for age, parity, smoking status, and other risk factors, women in the highest quintile of total vitamin D intake (median, 706 IU/d) had a relative risk of 0.59 (95% confidence interval, 0.40-0.86) compared with those in the lowest quintile (median, 112 IU/d) (P = .01 for trend). The intake of calcium from food sources was also inversely related to PMS; compared with women with a low intake (median, 529 mg/d), participants with the highest intake (median, 1283 mg/d) had a relative risk of 0.70 (95% confidence interval, 0.50-0.97) (P = .02 for trend). The intake of skim or low-fat milk was also associated with a lower risk (P<.001). CONCLUSIONS: A high intake of calcium and vitamin D may reduce the risk of PMS. Large-scale clinical trials addressing this issue are warranted. Given that calcium and vitamin D may also reduce the risk of osteoporosis and some cancers, clinicians may consider recommending these nutrients even for younger women.

Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects.

The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2,500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM; 19:00 to 21:00 h), or (3) dim (< 10 lux) red evening light (RED). In PMDD subjects, during the luteal phase compared to the follicular menstrual cycle phase, melatonin onset time was delayed, duration was compressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was decreased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the authors' previous observation that nocturnal melatonin concentrations are decreased in women with PMDD and suggest specific effects of light therapy on melatonin circadian rhythms that are associated with mood changes in patient versus control groups. The differential changes in onset and offset times during the menstrual cycle, and in response to AM and PM bright light compared with RED light, support a two-oscillator (complex) model of melatonin regulation in humans.

Thyroid axis function during the menstrual cycle in women with premenstrual syndrome.

Fifteen women with premenstrual syndrome (PMS) and 15 control women were tested twice for thyroid axis measures, once during the follicular and once during the luteal phase of the menstrual cycle. While PMS and control women did not differ in mean hormone values during either phase of the menstrual cycle, PMS women showed significantly greater variability in hormone measures including TSH, T3 uptake, T4, and FTI relative to controls. These findings are consistent with the conceptualization that, for a subset of women with PMS, thyroid axis abnormalities may contribute to their disorder. Additionally, when analyzed in the sample as a whole, the menstrual cycle exerted a significant effect on reverse T3 with greater levels observed in the luteal relative to the follicular phase of the cycle.

Neuroendocrine effects of light therapy in late luteal phase dysphoric disorder.

In 20 late luteal phase dysphoric disorder (LLPDD) and in 11 normal control (NC) subjects, circadian profiles of cortisol, prolactin, thyrotropin-stimulating hormone (TSH), and core body temperature were measured during midfollicular (MF) and late luteal (LL) menstrual cycle phases and after 1 week of light therapy either with (1) bright (tau 2500 lux) white morning (6:30 AM to 8:30 AM), (2) bright white evening (7 PM to 9 PM) or (3) dim (< 10 lux) red evening light, randomly administered in three separate luteal phases. In NC but not PMDD subjects, the cortisol peak significantly delayed in the LL compared with the MF phase. In PMDD, prolactin peak and amplitude were higher, prolactin acrophase earlier, and temperature amplitude higher during both the MF and LL phases. After light treatment, prolactin amplitude remained higher in LLPDD than in controls. In both groups, bright light shifted the cortisol acrophase, and AM light increased the prolactin nadir. Bright PM light increased the TSH nadir in LLPDD, but decreased it in controls. Thus, menstrual cycle phase, diagnosis, and light therapy may differentially affect neuroendocrine systems.