Striatal dopamine D2-type receptor availability and peripheral 17ß-estradiol.

Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17ß-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17ß-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17ß-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness.

Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterations in women who use oral contraceptive pills (OCPs) compared to naturally-cycling women. The goal of this study, therefore, was to determine whether there is an effect of OCPs on MRI measures of prefrontal cortical brain structure that may influence regulation of mood. We performed a double-blind, placebo-controlled, randomized crossover study comparing effects of OCPs (0.15 mg levonorgestrel + 0.30 µg ethinyl estradiol) vs placebo (N = 26) on MRI measures of prefrontal cortical thickness and on mood, as indicated by self-report on the Daily Record of Severity of Problems, which also includes one item related to somatic symptoms. MRI measures that reflect cortical thickness were smaller bilaterally in the pars triangularis and in the pars opercularis and frontal pole of the right hemisphere during the OCP arm vs. placebo. Only the effect in the right pars triangularis survived multiple comparisons correction. Right pars triangularis MRI measures of cortical thickness were not related to mood symptoms, but negatively correlated across conditions with severity of somatic symptoms on the DSRP. The somatic symptoms and MRI measures may be independently related to the actions of steroid hormones in OCPs, with OCPs simultaneously inducing both more effects on MRI measures of cortical thickness and somatic symptoms.

Brain activation during emotion regulation in women with premenstrual dysphoric disorder.

BACKGROUND: Difficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD. METHODS: On the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle. RESULTS: Women with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants. CONCLUSIONS: During the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

Pain Catastrophizing Predicts Menstrual Pain Ratings in Adolescent Girls with Chronic Pain.

OBJECTIVES: The current study aimed to explore relationships among self-reported menstrual pain ratings, acute laboratory pain, pain catastrophizing, and anxiety sensitivity in a sample of girls without pain (No Pain group) and girls with a chronic pain condition (Chronic Pain group). SETTING: A laboratory at an off-campus Medical School office building. SUBJECTS: Eighty-four postmenarchal girls (43 No Pain, 41 Chronic Pain) ages 10-17 participated in the study. METHODS: All participants completed self-report questionnaires assessing menstrual pain, pain catastrophizing, and anxiety sensitivity and completed a cold pressor task. Pain intensity during the task was rated on a 0 (no pain) to 10 (worst pain possible) numeric rating scale. RESULTS: After controlling for age, average menstrual pain ratings (without medication) were significantly correlated with cold pressor pain intensity for the No Pain group only. In the Chronic Pain group, menstrual pain ratings were significantly correlated with pain catastrophizing and anxiety sensitivity. In a multiple linear regression analysis, after controlling for age, only pain catastrophizing emerged as a significant predictor of menstrual pain ratings in the Chronic Pain group. CONCLUSION: Results demonstrate differences in relationships among menstrual pain, acute laboratory pain, and psychological variables in girls with no pain compared with girls with chronic pain. In addition, pain catastrophizing may be a particularly salient factor associated with menstrual pain in girls with chronic pain that warrants further investigation.

Emotion regulation in women with premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

Symptom-associated alterations in functional connectivity in primary and secondary provoked vestibulodynia.

ABSTRACT: Primary provoked vestibulodynia (PVD) is marked by the onset of symptoms at first provoking vulvar contact, whereas secondary PVD refers to symptom onset after some period of painless vulvar contact. Different pathophysiological processes are believed to be involved in the development and maintenance of primary PVD and secondary PVD. The primary aim of this study was to test the hypotheses that the resting state functional connectivity of the brain and brain stem regions differs between these subtypes. Deep clinical phenotyping and resting state brain imaging were obtained in a large sample of a women with primary PVD (n = 46), those with secondary PVD (n = 68), and healthy control women (n = 94). The general linear model was used to test for differences in region-to-region resting state functional connectivity and psychosocial and symptom assessments. Direct statistical comparisons by onset type indicated that women with secondary PVD have increased dorsal attention-somatomotor network connectivity, whereas women with primary PVD predominantly show increased intrinsic resting state connectivity within the brain stem and the default mode network. Furthermore, compared with women with primary PVD, those with secondary PVD reported greater incidence of early life sexual abuse, greater pain catastrophizing, greater 24-hour symptom unpleasantness, and less sexual satisfaction. The findings suggest that women with secondary PVD show greater evidence for central amplification of sensory signals, whereas women with primary PVD have alterations in brain stem circuitry responsible for the processing and modulation of ascending and descending peripheral signals.

Multilevel local anesthetic nerve blockade for the treatment of generalized vulvodynia: a pilot study.

INTRODUCTION: Vulvodynia is a common pain disorder among women with a major impact on sexual functioning and quality of life. There are few published studies addressing the treatment of the pain of generalized vulvodynia or of generalized vulvodynia accompanying localized pain in the region of the vulvar vestibule. AIM: A prospective, noncontrolled pilot study was conducted to assess the efficacy of a novel treatment using caudal epidural, pudendal nerve block, and vulvar infiltration of local anesthetic agents. MAIN OUTCOME MEASURES: The main outcome measure was vulvar pain as assessed by the McGill Pain Questionnaire (MPQ). The secondary outcome measures were depressed mood evaluated with the Beck Depression Inventory (BDI) and sexual functioning assessed by the Female Sexual Functioning Inventory (FSFI). METHODS: Thirty-two women with vulvodynia met inclusion criteria and 26 women completed the study. The protocol included five treatment sessions with multilevel local anesthetic nerve blockade and a follow-up contact or visit 2-3 months later. RESULTS: There were significant improvements in vulvar pain as determined by both the sensory and affective components of the MPQ and in depression as assessed by the BDI. However, there were no changes in sexual functioning on the FSFI. CONCLUSION: Serial multilevel nerve block administered for the treatment of vulvodynia is a neurophysiologically based modality that may be effective and merits a placebo-controlled study.

Neuroactive steroids after estrogen exposure in depressed postmenopausal women treated with sertraline and asymptomatic postmenopausal women.

Neuroactive steroids (NAS) allopregnanolone (ALLO), Allotetrahydrodeoxycorticosterone (THDOC) and dehydroepiandrosterone (DHEA) are important in the regulation of mood and behavior. Knowledge about these steroids in postmenopausal depression and the effect of estrogen on NAS is lacking. We elected to determine if there were differences in NAS between postmenopausal depressed women and age matched controls. We also investigated the effect of estradiol on NAS in post menopausal depressed women receiving a selective serotonin reuptake inhibitor (SSRI), and in non-depressed postmenopausal controls. As part of a previously published double blind study on estrogen acceleration of antidepressant action, post menopausal women with major depression receiving sertraline and healthy non depressed controls were randomized to transdermal estrogen patch 0.1 mg or placebo. NAS were measured at baseline and after 10 weeks of treatment. Depressed subjects were treated with sertraline 50 mg/day to 100 mg/day for 9 weeks. At the baseline and after treatment ALLO and DHEA were significantly lower in depressed women compared to controls. Although all depressed subjects experienced a positive clinical response, estrogen administration was not associated with changes in NAS in either the depressed or the asymptomatic postmenopausal women. The lower ALLO and DHEA in postmenopausal depressed women suggests that symptoms of depression may be influenced by the synthesis or fluctuation of these NAS. Estradiol exposure did not alter ALLO, DHEA, or THDOC, implying these NAS are unlikely to play a role in any mood changes in post menopausal women given estrogen therapy.

Ecological Momentary Assessment of Non-Menstrual Pelvic Pain: Potential Pathways of Central Sensitization in Adolescents and Young Adults with and without Primary Dysmenorrhea.

PURPOSE: Primary dysmenorrhea (PD; menstrual pain without an identified organic cause) has been proposed as a possible risk factor for the development of chronic pelvic pain, but the mechanism through which this process occurs is unknown. One possible mechanism is central sensitization - alterations in the central nervous system that increase responsiveness to pain leading to hypersensitivity. Repeated episodes of pain, such as those experienced over time with PD, may alter how the brain processes pain. Ecological momentary assessment (EMA; collection of data in real time in participants' natural environments) is a novel data collection method that may help elucidate pain occurring during non-menstrual cycle phases. PATIENTS AND METHODS: The current observational study assessed the feasibility and acceptability of using EMA via text messages to collect pelvic pain data during menstrual and non-menstrual cycle phases in a community sample of adolescents and young adults (AYA) aged 16-24 years with and without PD and explored occurrence rates and intensity of non-menstrual pelvic pain (NMPP) in each of these groups. RESULTS: Thirty-nine AYA with PD and 53 healthy controls reported pelvic pain level via nightly text message. Global response rate was 98.5%, and all participants reported that the EMA protocol was acceptable. AYA with PD reported higher intensity (2.0 vs 1.6 on 0-10 numeric rating scale; p=0.003) and frequency (8.7% vs 3.1% of days; p=0.004) of NMPP compared to healthy controls. CONCLUSION: The EMA protocol was feasible and acceptable. Though both the intensity and frequency of NMPP were low and at levels that would not typically warrant clinical assessment or intervention, these repeated nociceptive events may represent a potential mechanism contributing to the transition from cyclical to chronic pelvic pain in some individuals.

Effectiveness of transdermal nicotine patch in premenopausal female smokers is moderated by within-subject severity of negative affect and physical symptoms.

RATIONALE: Nicotine patches may be less effective in female compared with male smokers. However, it is unknown if negative affect and physical symptoms influence transdermal nicotine patch-related effects on smoking behaviors. METHODS: Eighty-one acutely tobacco-abstinent premenopausal female smokers attended three counter-balanced experimental sessions across the menstrual cycle (early follicular, late follicular, and mid-luteal) and were randomized to patch condition (nicotine [21 mg] vs. placebo [0 mg] transdermal patch). Negative affect and physical symptoms were assessed prior to patch administration. The patch was removed 5 h post-administration, and participants completed a smoking reinstatement task. Multilevel linear models tested associations of patch condition, negative affect and physical symptoms, and their interaction on smoking behavior. RESULTS: There was a significant patch condition × Negative Affect and Pain symptoms interaction on the number of cigarettes smoked (p < 0.05). When Negative Affect and Pain were lower-than-usual, females administered a nicotine patch smoked significantly fewer cigarettes than females administered a placebo patch (p < .05), but there were no significant patch differences when Negative Affect and Pain were higher-than-usual. There was also a significant patch condition × Negative Affect interaction on time delay. The effects of patch condition on time delay to smoking were greater during sessions in which Negative Affect was higher-than-usual. CONCLUSIONS: Results suggest that among female smokers transdermal nicotine patch effectiveness may interact with negative affect and pain. Understanding and considering female-specific factors that may impact the efficacy of one of the most commonly used cessation medications is important for improving smoking cessation in female smokers.

Contraception counseling for women with premenstrual dysphoric disorder (PMDD): current perspectives.

Premenstrual Dysphoric Disorder (PMDD) is a severe form of premenstrual syndrome (PMS) affecting up to 7% of reproductive age women. Women with PMDD are of reproductive age; therefore, contraception and treatment of PMDD are important considerations. The disorder as described in the DSM-V is characterized by moderate to severe psychological, behavioral and physical symptoms beginning up to two weeks prior to menses, resolving soon after the onset of menstruation and significantly interfering with daily functioning. PMDD develops in predisposed individuals after they are exposed to progesterone at the time of ovulation. It has been hypothesized that PMDD is in part attributable to luteal phase abnormalities in serotonergic activity and to altered configuration of ℽ-aminobutyric acid subunit A (GABAA) receptors in the brain triggered by the exposure to the neuroactive steroid progesterone metabolite, allopregnanolone (Allo). A large body of evidence suggests that selective serotonin reuptake inhibitors (SSRIs) can be effective in the treatment of PMDD. Combined hormonal contraceptive (CHC) pills, specifically the 20 mcg ethinyl estradiol/3mg drospirenone in a 24/4 extended cycle regimen has been shown to significantly improve the emotional and physical symptoms of PMDD. Other combined monophasic, extended cycle hormonal contraceptive pills with less androgenic progestins may also be helpful, although not well studied. Copper intrauterine devices (IUDs) are recommended for those not seeking hormonal contraceptives. Progestin-only methods including the progestin-only pill (POP), levonorgestrel (LNG) IUD, etonorgestrel implant or depot medroxyprogesterone acetate (DMPA) have the potential to negatively affect mood symptoms for women with or without baseline mood disorders, including PMDD. Careful counseling and close follow-up is recommended for patients with PMDD seeking these contraceptive methods.

Resting-state functional connectivity in women with PMDD.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls. METHODS: Thirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated. RESULTS: Nonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Experimental evaluation of central pain processes in young women with primary dysmenorrhea.

Primary dysmenorrhea (PD; menstrual pain without an underlying medical condition) is associated with enhanced pain sensitivity and temporal summation (TS) in adult women, which may reflect the presence of central pain processes. Research in this area has been limited by focusing on only adult populations and incomplete assessments of central sensitization. The current study explored both excitatory and inhibitory measures of pain processing in girls and young adult women with and without PD. Thirty-two young women with PD and 34 healthy controls underwent laboratory pain testing during each of 3 menstrual cycle phases (menstrual, ovulatory, and midluteal), which included measures of pain tolerance and threshold, TS, and conditioned pain modulation. Results indicated enhanced pain sensitivity in young women with PD as measured by heat pain tolerance and Average Pain50 (P50), compared with healthy controls. These group differences were evident at all phases of the menstrual cycle. No group differences in cold pain tolerance, TS, or conditioned pain modulation were evident at any phase of the menstrual cycle. These data suggest some evidence of central sensitization in young women with PD, although no evidence of enhanced excitatory or deficient inhibitory mechanisms were observed. Future research should focus on identifying other potential phenotypes for PD to determine those at risk of developing other pain problems.

Multilevel local anesthetic nerve blockade for the treatment of vulvar vestibulitis syndrome.

OBJECTIVE: Vulvar vestibulitis syndrome is a major cause of dyspareunia. This pilot study was designed to evaluate a novel treatment approach. STUDY DESIGN: This is a prospective study of 27 women with vulvar vestibulitis. The protocol included 5 treatment sessions with caudal epidural, pudendal nerve block, and vestibular infiltration of local anesthetic agents. RESULTS: There were significant improvements in vestibular pain as determined by the vulvalgesiometer, McGill pain questionnaire, self-report, and the Female Sexual Functioning Inventory. CONCLUSION: Serial multilevel nerve blocks administered for the treatment of vulvar vestibulitis is a conceptually neurophysiologically based modality that may be effective and merits a placebo-controlled study.

Premenstrual syndrome and premenstrual dysphoric disorder in adolescents.

PURPOSE OF REVIEW: To review the current knowledge about the prevalence, diagnosis, and management of premenstrual syndromes in adolescents. RECENT FINDINGS: Large epidemiologic studies addressing adolescent premenstrual disorders, clinical presentation, and comorbidity with other disorders have yet to be performed. Randomized controlled treatment trials for teens with moderate-to-severe premenstrual syndrome or the more severe affective predominant, premenstrual dysphoric disorder still are sorely lacking. This review will present an updated review of the published studies with respect to premenstrual syndrome and premenstrual dysphoric disorder in adolescents in the context of the large body of literature regarding presentation, diagnosis, and treatment in adult women. SUMMARY: Premenstrual disorders likely start in the teen years. At least 20% of adolescents may experience moderate-to-severe premenstrual symptoms associated with functional impairment. Current treatment includes lifestyle recommendations and pharmacologic agents that suppress the rise and fall of ovarian steroids or augment serotonin.

YAZ in the treatment of premenstrual dysphoric disorder.

Premenstrual disorders negatively affect millions of U.S. women. The premenstrual disorder at the most severe end of the spectrum is premenstrual dysphoric disorder (PMDD). The specific diagnostic criteria developed for PMDD and the availability of validated symptom diaries have allowed a more organized study of severe premenstrual disorders. The U.S Food and Drug Administration has now approved 4 agents for the treatment of PMDD: 3 antidepressants (i.e., selective serotonin reuptake inhibitors) and 1 low-dose combination oral contraceptive (COC) that contains the progestin drospirenone and is administered using a regimen of 24 days of active pills in a 28-day cycle (drospirenone/20EE-24/4). Drospirenone is unique among progestins used in COCs in that it has both antimineralocorticoid and antiandrogenic activities. Two pivotal studies have shown drospirenone/20EE-24/4 to be effective in treating the mood, physical and behavioral symptoms of PMDD and symptoms specifically associated with food, water retention and negative interpersonal relationships.

Rates of Anovulation in Adolescents and Young Adults with Moderate to Severe Primary Dysmenorrhea and Those without Primary Dysmenorrhea.

STUDY OBJECTIVE: To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea. DESIGN: Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale. SETTING: A university-based clinical research laboratory. PARTICIPANTS: Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls. INTERVENTIONS AND MAIN OUTCOME MEASURES: Rates of presumptive anovulation. RESULTS: One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05). CONCLUSION: Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. PERSPECTIVE: Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system.

Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment.

OBJECTIVE: The decline in concentrations of gonadal hormones during menopause gives rise to a range of physiologic and psychologic changes that may impact a woman's health and quality of life significantly. Most notable among these are vasomotor symptoms (hot flashes and night sweats) and mood and sleep disturbances. STUDY DESIGN: This article reviews the physiologic condition underlying menopausal vasomotor symptoms and centrally active, nonhormonal therapies that have demonstrated efficacy for their treatment. RESULTS: Despite the emergence of a range of nonhormonal treatments for vasomotor symptoms, a need still exists for safe and effective therapeutic options that directly target the underlying thermoregulatory mechanisms for women who want treatment but prefer to avoid hormone therapy or for whom hormone therapy is contraindicated. CONCLUSION: The availability of centrally active therapies for menopausal vasomotor symptoms with risks and benefits clearly defined by results from well-designed clinical trials has the potential to allay safety concerns that are associated with the treatment of these common symptoms.

Neurophysiologic changes during estrogen augmentation in perimenopausal depression.

BACKGROUND: Estrogen augmentation of antidepressant medication has been an effective treatment in a subgroup of women experiencing affective symptoms during perimenopause. It has been suggested that estrogen facilitates serotonergic transmission in brain regions involved in mood disorders. We investigated differences in physiologic brain changes with estrogen augmentation in women with perimenopausal depression who reached remission compared to those who did not reach remission. We also assessed whether such changes were correlated with serum hormone levels. METHODS: Quantitative electroencephalography (QEEG) was used to examine neurophysiologic brain changes in remission and non-remission of depressive symptoms. Women with major depressive disorder (MDD) in partial remission who were taking antidepressant medication for a minimum of 8 weeks and were experiencing two or more perimenopausal symptoms (hot flashes, night sweats, irregular periods, memory impairment, vaginal dryness) were recruited from the community. Absolute power, relative power, and QEEG cordance, a measure that has moderately strong associations with cerebral perfusion, were obtained before and after 6 weeks of treatment with 0.625 mg of conjugated estrogen per day. RESULTS: Women who experienced remission of depressive symptoms (Ham-D< or =7) had a significant decrease in right frontal QEEG cordance (p=0.008, t((8))=-3.54) which was not present in non-remitters. No significant correlations were found between hormone levels and QEEG cordance. CONCLUSION: In women with perimenopausal depression, physiologic brain changes in the right frontal region during estrogen augmentation were associated with remission of depression.