Menstrual Cycle-related Changes Research Articles

Targeting temporomandibular disorder pain treatment to hormonal fluctuations: A randomized clinical trial

Mounting evidence supports the importance of hormonal fluctuations in temporomandibular disorder (TMD) pain among women. Stabilizing influential hormones or having a plan and skills for coping with hormonally related increases in TMD pain, therefore, may be beneficial for women with TMD pain. This randomized clinical trial evaluated the short- and long-term efficacy of 3 interventions for women with TMD pain: (1) dental hygienist-delivered pain self-management training (SMT; n = 59); (2) the same dental hygienist-delivered pain self-management training, but with a focus on menstrual cycle-related changes in pain and other symptoms (targeted SMT, or TSMT; n = 55); and (3) continuous oral contraceptive therapy (6-month trial) aimed at stabilizing hormones believed to be influential in TMD pain (COCT; n = 57). Study participants completed outcome (pain, activity interference, depression) and process (pain beliefs, catastrophizing, coping effectiveness) measures before randomization, and 6 and 12 months later. Intent-to-treat analyses supported the benefits of the SMT and TSMT interventions relative to COCT. Targeting the self-management treatment to menstrual cycle-related symptoms did not increase the treatment’s efficacy. The benefits of the self-management interventions relative to COCT for pain and activity interference were statistically significant at 12 months, but not at 6 months, whereas the benefits for the process measures generally were apparent at both time points. COCT was associated with multiple adverse events (none serious). The study provides further support for long-term benefits of a safe, low-intensity (2 in-person sessions and 6 brief telephone contacts), dental hygienist-delivered self-management treatment for TMD pain.

Effect of Menstrual Cycle Phase on Dopamine D2 Receptor Availability in Female Cynomolgus Monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.

Unusual manifestations of premenstrual syndrome

The authors have identified six unusual manifestations of premenstrual syndrome: (i) typical premenstrual dysphoric disorder symptoms during ovulation; (ii) upper airway infection in the premenstrual phase that remits after onset of menstruation; (iii) recurrent perimenstrual erythematous and edematous skin plaques; (iv) hypomanic or manic state 2-3 days before onset of menstruation; (v) auditory hallucinations and delusion of reference, present only premenstrually; and (vi) remitted bipolar disorder presenting with premenstrual psychotic features. Psychiatrists should be aware of menstrual cycle-related changes in mental illness, physical illness, or both in women of reproductive age, if cyclic trends are suspected.

Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women

Circulating levels of the neuro-hypophysial nonapeptide oxytocin increase during sexual arousal and orgasm in both men and women. A few studies have evaluated the effect of the menstrual cycle on plasma oxytocin in normally cycling, sexually active, healthy fertile women using or not using contraceptive pills. In 20 ovulating women and 10 women taking an oral contraceptive (group 1 and group 2, respectively), sexual function, hormonal profile, and plasma oxytocin (OT) were evaluated throughout the menstrual cycle. In group 1, plasma OT was significantly lower during the luteal phase in comparison with both the follicular and ovulatory phases. Plasma oxytocin was significantly correlated with the lubrication domain of the Female Sexual Function Index (FSFI) during the luteal phase and showed a trend towards statistical significance during the follicular phase. In group 2, plasma OT did not show any significant fluctuation throughout the menstrual cycle, even though a significant correlation was evident with both the arousal and the lubrication domain of the FSFI during the assumption of the contraceptive pill. These findings suggest that plasma OT fluctuates throughout the menstrual cycle in normally cycling healthy fertile women with adequate sexual activity but not taking any oral contraceptive pill. Moreover, plasma OT levels significantly relates to the genital lubrication in both women taking and not taking oral contraceptive pill apparently confirming its role in peripheral activation of sexual function.

Hormonal manipulation in women with chronic, cyclic irritable bladder symptoms and pelvic pain

Objective: Chronic, painful bladder symptoms are diagnostic and therapeutic challenges for urologists and gynecologists. The aims of this study were to evaluate women with menstrual cycle-related changes in their interstitial cystitis symptoms, to treat them with hormonal manipulation, and to follow them long term. Study Design: The cases of women who were referred to a tertiary care center with interstitial cystitis and menstrual cycle exacerbation of symptoms were evaluated in a retrospective study. Fifteen women had undergone laparoscopy that was followed immediately by cystoscopy and bladder hydrodistension. Patients were then treated with leuprolide acetate or oral contraceptive pills. Results: Patient age ranged from 23 to 48 years. The duration of symptoms ranged from 1 to 26 years. Ten patients (67%) had findings of both interstitial cystitis and peritoneal endometriosis. Five of 15 patients (33%) had interstitial cystitis, but no endometriosis was found. Symptoms improved for 8 of 9 women who were treated with leuprolide acetate and for 5 of 6 women who were treated with oral contraceptive pills. Patients were followed up for an average of 55 months. Conclusion: Diagnostic laparoscopy should be considered together with hydrodistension of the bladder for women with pelvic pain and irritative bladder symptoms that are exacerbated premenstrually. Endometriosis is often present in patients with these complex symptoms. This is the first report of hormonal treatment for chronic, cyclic irritative bladder symptoms; improvement appears to occur even when endometriosis is not identified by laparoscopy. (Am J Obstet Gynecol 2002;186:1268-73.)

Gender-based differences and menstrual cycle-related changes in specific diseases: implications for pharmacotherapy.

Pharmacists should be aware of gender-based differences and menstrual cycle-related changes in six diseases: asthma, arthritis, migraine, diabetes, depression, and epilepsy. In general, women report symptoms of physical illness at higher rates, visit physicians more frequently, and make greater use of other health care services than men. Whereas reasons for these gender differences are not fully clear, a combination of biologic, physiologic, social, behavioral, psychologic, and cultural factors most likely contributes. A significant percentage of women with asthma, arthritis, migraine, diabetes, depression, or epilepsy experience worsening of their disease premenstrually. The mechanism is unknown, but is speculated to be multifactorial because of many endogenous and exogenous modulators and mediators of each disease. As part of general therapy for cycle-related exacerbations of any one of these disorders, patients should be encouraged to use a menstrual calendar to track signs and symptoms for two to three cycles; if cyclic trends are identified, the women should anticipate exacerbations and avoid triggering factors. Cyclic modulation with pharmacotherapy may be attempted. If unsuccessful, a trial of medical ovulation suppression with a gonadotropin-releasing hormone (GnRH) analog may be warranted. If that is successful, continuous therapy with a GnRH analog and steroid add-back therapy or less expensive alternatives may be effective. If pharmacotherapy is impractical, hysterectomy and bilateral oophorectomy with estrogen replacement therapy is a last resort. Gender differences and menstrual cycle-related changes are important areas for clinical and mechanistic research.

Healthy women and patients with endometriosis show high concentrations of inhibin A, inhibin B, and activin A in peritoneal fluid throughout the menstrual cycle.

Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.

Effects of the menstrual cycle on medical disorders.

Exacerbation of certain medical conditions at specific phases of the menstrual cycle is a well-recognized phenomenon. We review the effects of the menstrual cycle on medical conditions, including menstrual migraine, epilepsy, asthma, rheumatoid arthritis, irritable bowel syndrome, and diabetes. We discuss the role of medical suppression of ovulation using gonadotropin-releasing hormone agonists in the evaluation and treatment of these disorders. Peer-reviewed publications from English-language literature were located via MEDLINE or from bibliographies of relevant articles. We reviewed all review articles, case reports and series, and therapeutic trials. Emphasis was placed on diagnosis and therapy of menstrual cycle-related exacerbations of disease processes. Abrupt changes in the concentrations of circulating ovarian steroids at ovulation and premenstrually may account for menstrual cycle-related changes in these chronic conditions. Accurate documentation of symptoms on a menstrual calendar allows identification of women with cyclic alterations in disease activity. Medical suppression of ovulation using gonadotropin-releasing hormone agonists can be useful for both diagnosis and treatment of any severe, recurrent menstrual cycle-related disease exacerbations.

Stability of serum interleukin-10 levels during the menstrual cycle.

Menstrual cycle-associated variability in the circulating levels of several cytokines can be a confounding factor in measurements of in vivo cytokine levels in clinical studies. Since pregnancy-associated increases in interleukin-10 (IL-10) levels are well documented, we have investigated the variability in serum levels of IL-10 in healthy women at different stages of the menstrual cycle to ascertain whether this is a problem in comparative studies of circulating IL-10 levels. We obtained fifty-four successive serum samples at points in the menstrual cycles of 12 healthy fertile women, precisely timed by measurement of the luteinizing hormone surge, and measured the interleukin-10 levels. Levels of IL-10 in successive serum samples from each woman taken on days LH - 7 (that is seven days prior to LH surge), LH - 4, LH + 1, LH + 7, and LH + 10 showed that IL-10 does not vary in a systematic way during the menstrual cycle. These results validate the sampling of women in studies of IL-10 levels in various clinical situations and establish that these levels are not dependent on menstrual cycle dates. They also suggest that menstrual cycle-related changes in IL-1 are not mediated by IL-10. The rise in progesterone in the luteal phase of the menstrual cycle is not mirrored by a rise in the circulating IL-10 level, which implies either that the pregnancy-associated rise is not related to progesterone or that it is only observed at the higher progesterone levels in pregnancy.

Premenarcheal expectations and postmenarcheal experiences of positive and negative menstrual related changes

Longitudinal examination of early adolescent girls' premenarcheal expectations and postmenarcheal experiences of positive and negative menstrual related changes. Ratings of 14 positive and negative changes were made by 80 girls on three occasions: (1) in grade 6 when girls were premenarcheal, (2) at the test occasion within six months after each girls' own menarche, and (3) in grade 9 when girls were postmenarcheal. Premenarcheal girls rated expectations of changes, and postmenarcheal girls rated experiences of changes, for both premenstrual and menstrual phases. Girls also rated preparation for, and emotional response to, menarche and mothers' helpfulness on the first two occasions. Ratings for positive and negative changes were at similar levels premenarcheally and decreased at menarche; once menstruation became established, ratings of negative changes increased while those of positive changes decreased. Ratings for negative changes were higher in the menstrual phase, while ratings for positive changes were higher in the premenstrual phase. Premenarcheal expectations of changes contributed to the prediction of menarcheal experiences of changes. Premenarcheal expectations and menarcheal experiences, along with anticipated emotional response to menarche, contributed to the prediction of longer-term experience of negative changes; menarcheal experiences, along with preparation for and emotional response to menarche, contributed to the prediction of longer-term experience of positive changes. Both expectations about, and initial experiences of, menstrual cycle-related changes were associated with longer-term menstrual experiences. The different outcomes for positive and negative changes have implications for menstrual socialization, and provide the basis for some optimism about facilitating a more complex and multidimensional understanding of menstruation.

Perimenstrual symptoms: time course of symptom intensity in relation to endocrinologically defined segments of the menstrual cycle.

This investigation assessed the syndromal nature of menstrual cycle changes in women who experience significant cyclicity of mood by exploring the time course of different symptoms in relation to endocrinologically defined segments of the menstrual cycle. Participants were accepted into the protocol on the basis of a prospectively documented history of perimenstrual mood change. The protocol included completion of the Daily Life Experiences Questionnaire and blood sampling during three menstrual cycles. The syndromal nature of menstrual cycle changes was explored by determining the types of symptoms which fluctuated in relation to five endocrinologically defined segments of the menstrual cycle, and the time course of the symptom changes. The results further document the temporal association between the luteal phase and the onset of perimenstrual symptoms and suggest that the syndromal nature of menstrual cycle-related changes may differ for women who experience different intensities of cyclical mood.

Oral glucose tolerance during the menstrual cycle in normal women and women with alleged premenstrual "hypoglycemic" attacks: effects of naloxone.

To resolve existing controversies about the impact of the menstrual cycle on oral glucose tolerance, we examined the glucose, insulin, and glucagon responses to an oral glucose challenge at different phases of the menstrual cycle in five normal women (NW) and six women with premenstrual syndrome and alleged premenstrual hypoglycemic attacks (PMHA). Responses to oral glucose did not differ significantly between follicular and luteal phase studies in either group, nor were significant differences found between the responses of NW and women reporting PMHA. In parallel studies, the possible glucoregulatory effects of endogenous opiates were assessed. Concomitant infusion of naloxone altered neither the basal concentrations of glucose, insulin, and glucagon nor the responses of these measures to the glucose challenge. We conclude that NW and women with premenstrual syndrome and alleged PMHA have no menstrual cycle-related changes in glucose, insulin, or glucagon responses to an oral glucose load. The fact that four of six PMHA subjects had symptoms typical of hypoglycemia at glucose nadirs above 50 mg/dl suggests that an explanation other than hypoglycemia must be sought for such symptomatic episodes. Endogenous opiate peptides appear to exert no glucoregulatory effects at naloxone-sensitive receptor sites.

Psychiatric progress: Mood and the menstrual cycle

A majority of women are aware of menstrual cycle-related changes in mood and behaviour. Psychiatric disorders may also be influenced by the menstrual cycle. A premenstrual tension syndrome has been described. Research into the prevalence, actiology and management of this condition has been hampered by additions and alterations to the original description and methodological difficulties involved in menstrual cycle research. Biological, psychological and socialogical theories have been proposed to explain menstrual cycle-related mood changes. Our own studies have found evidence of ovarian steroid disturbances, and impaired psychological functioning in women with the premenstrual syndrome. Therapeutic approaches must consider both aspects. Medication often makes the patient more accessible and receptive to regimens aimed at increasing coping skills. More vigorous research into this disorder is needed.