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Premenstrual Dysphoric Disorder: Contemporary Diagnosis and Management
Abstract
Most ovulatory women experience premenstrual symptoms (premenstrual syndrome, molimina) which indicate impending menstruation and are of little clinical relevance because they do not affect quality of life. A few women, however, experience significant physical and/or psychological symptoms before menstruation that, if left untreated, would result in deterioration in functioning and relationships. The precise etiology remains elusive, although new theories are gaining support in pre-clinical and early clinical trials. Refined diagnostic criteria allow better discrimination of this condition from other psychiatric diagnoses and the selection of symptom appropriate therapies that afford relief for most women. Pharmacotherapies (particularly selective serotonin reuptake inhibitors and SNRIs) represent the first-line treatment for premenstrual dysphoric disorder and severe, mood-related premenstrual syndrome. Continuous combined oral contraceptives have limited evidence for usefulness in premenstrual dysphoric disorder, whereas medical ovarian suppression is often recommended for patients who fail to respond or cannot tolerate first-line treatments (e.g., selective serotonin reuptake inhibitors). The use of cognitive behavioural therapies is promising, but it remains limited by sparse data and restricted access to trained professionals. A proper diagnosis (particularly the distinction from other underlying psychiatric conditions) is crucial for the implementation of effective therapy and alleviation of this impairing condition.
... 7,8 When these alternatives failed, pharmacological options, as hormone replacement therapy, oral contraceptive pills, estrogen and progesterone, and selective serotonin reuptake inhibitors, have been used to reduce PMS symptoms. 9 Some women with PMS also use complementary and alternative therapies to improve symptoms 10 such as herbal medicine, homeopathy and exercises, 9,11 physical therapy treatments as manipulative therapies, phototherapy, transcutaneous electrical stimulation, massage, 9,11,12 yoga, 13 reflexology 14 and acupuncture. 15,16 Auriculotherapy, which consists of a non-invasive acupuncture technique performed by stimuli at ear specific points (pinna), [17][18][19] is not mentioned in the treatment PMS consensus. ...
... 7,8 When these alternatives failed, pharmacological options, as hormone replacement therapy, oral contraceptive pills, estrogen and progesterone, and selective serotonin reuptake inhibitors, have been used to reduce PMS symptoms. 9 Some women with PMS also use complementary and alternative therapies to improve symptoms 10 such as herbal medicine, homeopathy and exercises, 9,11 physical therapy treatments as manipulative therapies, phototherapy, transcutaneous electrical stimulation, massage, 9,11,12 yoga, 13 reflexology 14 and acupuncture. 15,16 Auriculotherapy, which consists of a non-invasive acupuncture technique performed by stimuli at ear specific points (pinna), [17][18][19] is not mentioned in the treatment PMS consensus. ...
... 30 The PSST consists of 19 items subdivided into two domains. The first domain included: 1) psychological symptoms (questions 1-4), behavioral/social (questions 5-8) and physical symptoms (questions [9][10][11][12][13][14]. The second domain rates the functional impact of these symptoms on work efficiency or productivity, relationships with coworkers and family, social life activities, and home responsibilities. ...
Objective
This study aimed to investigate the effect of auriculotherapy on the intensity of physical and mood Premenstrual syndrome (PMS) symptoms.
Design
Single-blind randomized, placebo-controlled clinical trial.
Setting
Federal University of Parana, Curitiba, Brazil.
Intervention
Ninety-one women were randomly assigned to Auriculotherapy (AG), Placebo (PG), and Control (CG) groups. The intervention was 8 weeks long, done once per week. At each session in AG the microneedles were placed in seven points related to PMS symptoms (Anxiety; Endocrine; Muscle relaxation; Analgesia; Kidney; Shen Men; and Sympathetic). At PG the microneedles also were placed in seven points but unrelated to PMS symptoms (Tonsils; Vocal cords; Teeth; Eyes; Allergy; Mouth; and External nose).
Main outcome measures
Assessments of PMS symptoms (Premenstrual Syndrome Screening Tool), musculoskeletal pain (Nordic Musculoskeletal Questionnaire), anxiety (Beck Anxiety Inventory), and quality of life (WHOQOL-Bref) were done at baseline, before the 5th session, after program completion, and a month follow-up.
Results
The AG and PG showed significantly lower scores of PMS symptoms, musculoskeletal pain, and anxiety. On the quality of life and follow-up analysis, the significance was observed only in PG.
Conclusion
Auriculotherapy can be used as adjunctive therapy to reduce the physical and mood PMS symptoms.
... Women who undergo from severe PMS, pharmacological treatment is the recommended, predominantly Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), included paroxetine, fluoxetine, sertraline, venlafaxine, citalopram, escitalopram, and duloxetine [26]. In most cases, antidepressants were used continuously, nonetheless in some other studies antidepressants were provided intermittently (only during the luteal phase) or were even narrowed to or initiated by the onset of PMS symptoms [9]. ...
... Continuous consumption seems to be effective to alleviate depressed mood and somatic (e.g., pain) symptoms. Additional antidepressants, such as fluvoxamine and bupropion, have not formed positive results and should not be selected as a first-line treatments for PMS [26]. ...
... In 2006, this medication met FDA approval for the treatment of severe PMS in women desiring oral contraception (Rapkin et al., 2019). The effectiveness of this particular COCs for reducing premenstrual symptoms may be due to its administration in a 24/4 regimen which delivers more stable hormone levels or to the unique antimineralocorticoid and anti-androgenic properties of drospirenone [26]. ...
Premenstrual Syndrome (PMS), is a worldwide phrase present
in all cultures and has been the subject of consideration for many
biomedical researchers. A large number of reproductive age
women experience at least some form of menstrual symptoms. The
severity and chronic nature of PMS has led to the prevalence of
this disorder in women and interrupts their work, family relationships,
and daily activities. Furthermost menstruating women (80-95%)
experience physiological changes in the premenstrual period. Many
Pharmacological and non-pharmacological methods employed
to remedy PMS symptoms. Therefore, physicians should modify
therapy based on patient tolerance and response to each medication.
Regarding diet, although “PMS diets” have been recommended, few
of the recommendations were founded on scientific fact. There is
a link between premenopausal women following a Western diet
containing high fat and low fiber with vegetarians exposed that a
low-fat vegetarian diet decreased plasma oestrogen levels and the
duration of premenstrual symptoms. Therefore, changing dietary
guidelines towards consuming more complex carbohydrates and
vegetables, proteins, less simple carbohydrates, animal proteins
and saturated fatty acids and increasing fiber intake. Severe PMS
symptoms have a negative impact on female students’ academic
performance; consequently, mental health professionals have a
major role in defining factors that buffer severity of PMS among
females.
... Women who undergo from severe PMS, pharmacological treatment is the recommended, predominantly Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), included paroxetine, fluoxetine, sertraline, venlafaxine, citalopram, escitalopram, and duloxetine [26]. In most cases, antidepressants were used continuously, nonetheless in some other studies antidepressants were provided intermittently (only during the luteal phase) or were even narrowed to or initiated by the onset of PMS symptoms [9]. ...
... Continuous consumption seems to be effective to alleviate depressed mood and somatic (e.g., pain) symptoms. Additional antidepressants, such as fluvoxamine and bupropion, have not formed positive results and should not be selected as a first-line treatments for PMS [26]. ...
... In 2006, this medication met FDA approval for the treatment of severe PMS in women desiring oral contraception (Rapkin et al., 2019). The effectiveness of this particular COCs for reducing premenstrual symptoms may be due to its administration in a 24/4 regimen which delivers more stable hormone levels or to the unique antimineralocorticoid and anti-androgenic properties of drospirenone [26]. ...
Premenstrual Syndrome (PMS), is a worldwide phrase present
in all cultures and has been the subject of consideration for many
biomedical researchers. A large number of reproductive age
women experience at least some form of menstrual symptoms. The
severity and chronic nature of PMS has led to the prevalence of
this disorder in women and interrupts their work, family relationships,
and daily activities. Furthermost menstruating women (80-95%)
experience physiological changes in the premenstrual period. Many
Pharmacological and non-pharmacological methods employed
to remedy PMS symptoms. Therefore, physicians should modify
therapy based on patient tolerance and response to each medication.
Regarding diet, although “PMS diets” have been recommended, few
of the recommendations were founded on scientific fact. There is
a link between premenopausal women following a Western diet
containing high fat and low fiber with vegetarians exposed that a
low-fat vegetarian diet decreased plasma oestrogen levels and the
duration of premenstrual symptoms. Therefore, changing dietary
guidelines towards consuming more complex carbohydrates and
vegetables, proteins, less simple carbohydrates, animal proteins
and saturated fatty acids and increasing fiber intake. Severe PMS
symptoms have a negative impact on female students’ academic
performance; consequently, mental health professionals have a
major role in defining factors that buffer severity of PMS among
females.
... Tratamiento quirúrgico: cuando existe poca respuesta al tratamiento con antidepresivos o con medicamentos supresores de la función ovárica, se considera el tratamiento quirúrgico con histerectomía y ooferectomía bilateral como la última línea de tratamiento para síndrome disfórico premenstrual con síntomas severos (2,14). Los estudios que se han realizado en este campo son pequeños pero los datos sugieren una mejoría e604 significativa en pacientes que no tuvieron respuestas con otras terapias (8), cuando se debe aplicar la cirugía como tratamiento se tiene que considerar los deseos de embarazo y tener en cuenta que deberá tomar terapia de remplazo hormonal hasta la edad de menopausia natural (2). ...
... Tratamiento quirúrgico: cuando existe poca respuesta al tratamiento con antidepresivos o con medicamentos supresores de la función ovárica, se considera el tratamiento quirúrgico con histerectomía y ooferectomía bilateral como la última línea de tratamiento para síndrome disfórico premenstrual con síntomas severos (2,14). Los estudios que se han realizado en este campo son pequeños pero los datos sugieren una mejoría e604 significativa en pacientes que no tuvieron respuestas con otras terapias (8), cuando se debe aplicar la cirugía como tratamiento se tiene que considerar los deseos de embarazo y tener en cuenta que deberá tomar terapia de remplazo hormonal hasta la edad de menopausia natural (2). ...
El síndrome disfórico premenstrual es un trastorno que afecta diversas esferas de la vida, provocando un detrimento funcional. En su etiología se implica la desregulación de hormonas y neurotransmisores, para su diagnóstico se utiliza los criterios del Manual diagnóstico y estadístico de los trastornos mentales, el DSM-V. El tratamiento con antidepresivo se considera la primera línea de tratamiento; el uso de anovulatorios como los de anticonceptivos y agonistas de la hormona liberadora de gonadotropina, pueden ser considerados sobre todo en pacientes que requieran control de la fertilidad y manejo de los síntomas. La cirugía se considera la última línea de tratamiento para pacientes que presentan sintomatología grave y difícil de controlar. Existen otras terapias como la alloprenanolona, terapia cognitivo conductual dieta y ejercicio que requieren futuras investigaciones para determinar su beneficio en el manejo de este trastorno.
... Selective serotonin reuptake inhibitors (SSRIs) are very efficacious and the first line pharmacologic treatment options for PMS/PMDD. However, about 40% of PMDD women do not respond to SSRIs [20,21]. Yonkers [22] found that sertraline treatment of PMDD significantly improved anxiety and depression, indicating that PMDD should be treated according to the classification. ...
Background:
Premenstrual dysphoric disorder (PMDD) is a common mental health challenge among women of reproductive age. Allopregnanolone (3α, 5α-THP; ALLO) mediated functional alterations of GABAA receptors (GABAA-R) are involved in PMDD pathogenesis, however, the specific mechanism remains unknown. Therefore, we investigated the role of ALLO mediated GABAA-Rα4 in the pathophysiology of PMDD.
Purpose:
We determined whether the pathogenesis of PMDD is associated with ALLO mediated GABAA-Rα4 expression changes in different brain regions.
Methods:
Rat models of PMDD liver-qi invasion syndrome (PMDD-LIS) were established via the resident intruder paradigm. Behavioral changes of rats were assessed by aggressive behavior tests, EPM and OFT. The levels of progesterone and ALLO in serum as well as brain areas were determined by ELISA. Variations in GABAA-Rα4 levels in brain regions were assessed by immunofluorescence and RT-PCR. Medicated serum was used to interfere with rat hippocampal neurons, and changes in Cl- current were recorded through electrophysiology.
Results:
Premenstrual anxiety and irritability of PMDD-LIS patients can be simulated in PMDD-LIS rat models. Exogenous ALLO significantly improved the anxiety behaviors of PMDD-LIS rats. Changes in ALLO among different brain regions varied. GABAA-Rα4 expressions were low in the amygdala and abnormally high in the hippocampus, however, ALLO alleviated these deviations. Whole-cell patch clamp recording technique showed a weaker Cl- current intensity of PMDD-LIS rats, reduced neuroinhibitory functions and increased Cl- current intensity in the ALLO group drug serum intervention and enhanced emotional inhibition function.
Conclusion:
We established that ALLO regulation of the GABAA-Rα4 subunit in the amygdala and hippocampus is involved in PMDD-LIS pathogenesis.
... Furthermore, a core feature of PMDD is the periodically changing symptoms based on the menstrual cycle. Thus, ovarian suppression or ovariectomy was often effective for some patients with PMS [29][30][31]. This study performed a series of related trials involving ovariectomy and hormone priming to verify our models' reliability. ...
Background:
Premenstrual dysphoric disorder (PMDD) is high in women of childbearing age with obvious premenstrual irritability. However, reliable animal models are still lacking.
Materials and methods:
PMDD rat model of premenstrual irritability was induced by the resident-intruder paradigm (RIP). Behavioral characteristics were determined by the aggressive behavior test, elevated plus maze, open-field test, and breast width measurement. The estrous cycle in rats was artificially manipulated by bilateral ovariectomy and exogenous hormone injection to verify the model phenotype's dependence on the estrous cycle. Fluoxetine and Baixiangdan capsules were administered by gavage to determine the symptom improvement effect of PMDD irritability. Biomarkers in serum and brain were detected using ELISA, and GABRA4 was detected in the brain by RT-PCR and Western blot.
Results:
Rat models demonstrated similar clinical characteristics as PMDD, such as premenstrual irritability and anxiety, and the above symptoms were estrous cycle-dependent. In addition, the levels of progesterone (P) and ALLO hormones decreased in the serum, hippocampus, amygdala, and frontal lobe in the NR phase. The contents of 5-HT in the brain were significantly increased, while NE and GABA contents were considerably reduced. Moreover, mRNA and protein expression of GABRA4 levels in model rats' amygdala, hippocampus, and frontal lobe were significantly increased, while drug intervention downregulated its expression in these tissues.
Conclusion:
Premenstrual irritability rat model of PMDD demonstrates a behavioral phenotype consistent with the clinical symptoms of PMDD and micro index. The increased levels of 5-HT, NE, and expression of GABRA4, as well as the decrease of GABA, P, and ALLO levels, may be critical biomarkers of the abnormal changes that occur during the pathogenesis of PMDD.
... A PMS-re és a PMDD-re való genetikai hajlammal kapcsolatban régóta kutatások zajlanak [11]. Egyes tanulmányok az ösztrogénreceptor-alfa (ESR1)-génnel való lehetséges összefüggésre utalnak [12]. ...
Premenstrual syndrome (PMS) is one of the most common problems for women of reproductive age worldwide, along with painful menstruation and genital inflammation. The physical, mental and behavioural symptoms recur during the luteal phase of the cycle and cause a deterioration in the quality of life, affecting the patient's social, work and family relationships. Symptoms typically disappear spontaneously within a few days after the onset of menstruation. A severe form of PMS is premenstrual dysphoric disorder (PMDD), which requires psychiatric management. The onset and severity of PMS with multifactorial pathogenesis is triggered by psychoneuroendocrine mechanisms that are influenced by the cyclical functioning of the hypothalamic-pituitary-ovarian axis, altering the neurotransmitter or neuropathway functions of the brain, e.g., the serotoninergic system. The psychoneuroendocrine mechanisms contribute to the development of physical, psychological and behavioural symptoms, which are also influenced by the combined presence of other physiological (genetical background, metabolic and chronic inflammatory processes, chronobiological and circadian disorders) and psychological stressors and their interaction. Orv Hetil. 2022; 163(25): 984-989.
... A strukturált interjúk, kérdőívek és a betegek önértékelő skáláinak használata jól bevált, és többféle validált diagnosztikus technika elérhető. Számos eszköz áll rendelkezésre, például A menstruációs tünetek hatásának és súlyosságának prospektív nyilvántartása (Prospective record of the impact and severity of menstrual symptoms -PRISM) [12] vagy A problémák súlyosságának napi nyilvántartási skálája (Daily record of severity of problems -DRSP) [13]. Ez utóbbi 17 gyakori PMS-tünetet tartalmaz, köztük 11 tünetet a Mentális zavarok diagnosztikai és statisztikai kézikönyvének ötödik kiadásában (DSM-5) szereplő PMDD diagnosztikai kritériumaiból. ...
A premenstruális szindróma (PMS) a reproduktív életkorú nők egyik leggyakoribb problémája. A fizikai, mentális és magatartásbeli tünetek a ciklus lutealis fázisában jelentkeznek visszatérően, és életminőség-romlást okoznak a mindennapi életben, befolyásolva a páciens szociális, munkahelyi és családi kapcsolatait. A tünetekre jellemző, hogy pár nap alatt a menstruáció kezdete után spontán eltűnnek. A PMS és a premenstruációs dysphoriás zavar (PMDD) diagnózisa a következő kritériumok alapján állítható fel a Premenstruális Rendellenességek Nemzetközi Társaságának (International Society for Premenstrual Disorders – ISPMD) ajánlása szerint: a PMS esetében a nőnek 1–4 tünete van, amelyek lehetnek fizikai, viselkedési vagy affektív/pszichológiai jellegűek, vagy minimum 5 tünettel rendelkezik, melyek fizikai vagy viselkedési jellegűek. Ha viszont egy nőnek 5 vagy több tünete van, és ezek közül az egyik affektív tünet (például ingerlékenység, hangulatingadozás, düh) a fizikai vagy viselkedési tünetek mellett, akkor a pontosabb PMDD diagnózisa állítható fel. A diagnózisok megerősítéséhez az általános és a nőgyógyászati anamnézis mellett a páciens által naponta kitöltött prospektív skálák, például a menstruációs tünetek hatásának és súlyosságának prospektív nyilvántartása, továbbá a problémák súlyosságának napi nyilvántartási skálája jelent segítséget. A terápiás terv kialakításakor fontos figyelembe venni a tünetek súlyosságát, a nő fogamzási terveit vagy fogamzásgátlási igényeit, a társuló egyéb betegségeit és a korábbi kezelési módszerekre adott válaszát. A terápiás lehetőségek közé tartozik – a PMS és a PMDD súlyosságától függően – a rendszeres aerob testmozgás, a stresszoldás, a kognitív viselkedésterápia, a gyógyszeres kezelések (szelektív szerotoninvisszavétel-gátlók, kombinált oralis ösztrogén-progesztin fogamzásgátlók, GnRH-agonisták). Orv Hetil. 2022; 163(26): 1023–1031.
... A great deal of PMS is still unknown to us [10]. This condition is one of the most troublesome and common complaints of women at their visits to healthcare facilities for which there is no definitive cure [11]. Therefore, there is a need for effective and acceptable palliative methods with no or low side effects for women with this problem. ...
Background:
Premenstrual syndrome (PMS) is a common problem of women of reproductive age, affecting various aspects of their lives. However, limited studies have investigated the effect of internet-based cognitive-behavioral therapy (ICBT) on PMS. Therefore, we aimed to assess whether ICBT can reduce symptom severity of women with PMS and improve their quality of life during the perimenstrual and late follicular phases of menstrual cycle.
Methods:
The study included 92 university students aged 18-35 years who had moderate to severe PMS. The participants were allocated into two groups of 46 using block randomization. The intervention group underwent ICBT for two menstrual cycles, while the control group received no intervention. Before and after the intervention, all participants filled the Daily Record of Severity of Problems (DRSP) for two menstrual cycles and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) on days 1-2 and 11-13 of the menstrual cycle. Data were analyzed using univariate general linear models.
Results:
Four students in the intervention group were lost to follow-up. Following the intervention, the mean score of total PMS symptoms was significantly lower in the intervention group than in the control group (10.4 vs. 20.2, adjusted difference: - 9.9 [95% CI - 13.3 to - 6.6]), and the score of perimenstrual quality of life was significantly higher (64.2 vs. 50.3, 14.1 [8.5 to 19.8]). However, there was no significant intergroup difference in the late follicular quality of life (68.3 vs. 67.3, 1.9 [- 4.4 to 8.1]).
Conclusions:
The ICBT could reduce the symptom severity of women suffering from PMS while improving their perimenstrual quality of life. However, it had no significant effect on the late follicular quality of life. Therefore, this intervention can be used for women with PMS. Trial registration The Iranian Registry of Clinical Trials, Identifier: IRCT20100414003706N34, Registered prospectively on 19 June 2019, https://www.irct.ir/trial/38394 .
... Finally, the relationship of hormones and mood (or affect) may be more complex than can be fully explained by the presence/absence of exogenous hormones. For example, the prevailing understanding of the etiology of Premenstrual Dysphoric Disorder is that a subset of women may be particularly susceptible to affective dysregulation caused by changes in endogenous hormone levels rather than absolute levels (Reid & Soares, 2018). Differential sensitivity to hormone fluctuation has also been implicated in the pathophysiology of postpartum depression (Bloch et al., 2000). ...
Background
Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank.
Methods
The analysis included 232 993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD.
Results
GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10 ⁻¹⁵ ]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression ( rg = 0.231, s.e. = 0.055, p = 2.8 × 10 ⁻⁵ ). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications.
Conclusions
These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3 ) are effective treatments for hot flashes.
... Drospirenone is used as a progestogen-only birth control pill on its own, in combination with estrogen, ethinyl estradiol, or estetrol (E4), with or without supplemental folic acid (vitamin B9), and for use in menopausal hormone therapy. For the treatment of moderate acne, premenstrual syndrome (Dickerson et al., 2003), premenstrual dysphoric disorder (Pearlstein, 2016Reid and Soares, 2018), and dysmenorrheal (Gomathy et al., 2019), a birth control pill with low-dose ethinyl estradiol is also indicated (painful menstruation). Moderate to severe vasomotor symptoms (hot flashes) (Freedman, 2014), vaginal atrophy, and postmenopausal osteoporosis (Maclennan et al., 2004;Torgerson and Bell-Syer, 2001) are appropriate uses of this medication. ...
The UPLC technique we have developed is completely unique and reliable and can quantitatively measure drospirenone and estetrol (E4) simultaneously. The chromatographic column of Luna C18 (100 × 2.6 mm, 1.6 µ) and isocratic elution, with a buffer (0.1% formic acid) and acetonitrile (30:70 v/v), using a flow of 1 ml/minutes at room temperature was used. The process was monitored by ultraviolet detection at 262 nm. A total of 3 minutes was dedicated to using a 3-minute timer to separate drospirenone and E4. Within the concentration range from 3 to 45 µg/ml of drospirenone and 14.2–213 µg/ml of E4, the analysis was completed in less than 5 minutes. System suitability parameters were studied and the outcomes were within acceptable limits when they were injected with the standard six times. To confirm the safety of the formulated product, a market-bought solution was assayed and it was found to be within specification. With all conditions and the acceptable range allowed, degradation studies were carried out on drospirenone and E4, all of which came back with a purity threshold that was higher than the purity angle. This particular technique was found to be consistent with the guidelines set forth by the International Council on Harmonization. © 2021. Rafi Syed and Rambabu Kantipudi. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
... About 80-90% of women in reproductive age have somatic and cognitive-emotional symptoms (Reid and Soares 2018) in the luteal phase of the menstrual cycle. It is estimated that 20 to 25% of women have premenstrual syndrome (PMS) and 1.2 to 5% of women meet diagnostic criteria for premenstrual dysphoric disorder (PMDD) (Phillips 2019). ...
Premenstrual dysphoric disorder (PMDD) affects 1.2 to 5% of women of reproductive age. Besides significant suffering and social, occupational, and interpersonal impairment, it has been suggested that this syndrome is associated with other affective disorders, in different reproductive phases, such as pregnancy and the postpartum period. However, the literature on this association is scarce and presents great variability in terms of adopted methodology and mixed results. To analyze the relationship between PMDD and other affective disorders, aiming to contribute to the clarification of whether PMDD can be considered a risk factor for perinatal depression (PND). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, PsycINFO databases. Seven original studies were included. Only one study linked PMDD with depression during pregnancy, with evidence of a positive association between PMDD and PND. This and five other studies show a positive relationship between PMDD and postpartum depression (PPD), assessed in periods ranging from 2 to 4 days to 1 year after birth. Only one study found no significant association between PMDD and PPD, assessed at 4 weeks postpartum. There seems to be a positive and significant association between PMDD and the development of perinatal depression, particularly postpartum depression. This review supports the relevance of health professionals systematically evaluating the presence of premenstrual dysphoric disorder, when monitoring women throughout the perinatal period.
... While around one in 20 menstruating women have PMDD [4], the disorder is underrecognized by clinicians and therefore often misdiagnosed or treated suboptimally [5,6]. In this review, we focus on challenges in diagnosing and treating PMDD, and recent treatment developments; for a general overview of PMDD diagnosis and treatment, we refer the reader to other reviews [7][8][9][10][11]. ...
... Despite some similarities in occupational competence problems observed between university students with PMDD and their peers without PMDD, the lower occupational competence scores in the PMDD group demonstrates a need for occupational therapy evaluation and interventions. Nonpharmacological treatment options for PMDD include stress management and cognitive behavioral therapy (Reid and Soares, 2018), which are frequently used in occupational therapy interventions (Sarsak, 2018). However, further research is needed to analyze the effectiveness of different occupational therapy interventions in women with PMDD. ...
Introduction
Premenstrual dysphoric disorder (PMDD) is defined as a mental health issue and is assessed using DSM-V diagnostic criteria. Premenstrual dysphoric disorder comprises emotional, behavioral, and physical symptoms that occur in the premenstrual phase and resolve shortly after the start of menstruation. These symptoms and functional impairment may negatively affect occupational competence and value. This study investigated perceived occupational competence and value in university students with premenstrual dysphoric disorder.
Methods
This cross-sectional study was performed at a public university with 35 students with PMDD and 35 age-matched students without PMDD. Occupational competence and value were evaluated using the Occupational Self-Assessment (OSA).
Results
There was a significant difference between the groups in OSA competence score ( p < 0.05), while there was no significant difference in OSA value score ( p > 0.05).
Conclusion
This study demonstrated that university students with PMDD experience more occupational competence challenges than peers without PMDD. Further studies should be performed to determine the role of occupational therapy in the rehabilitation of PMDD.
... Pharmacologic intervention for PMS includes hormone therapy and symptomatic treatment, including progesterone, oryzanol, vitamins, and oral antianxiety antidepressants [3]. Even though it works very well, evidence on the efficacy of sustained progesterone and the side effects of antidepressant and anxiolytics limited further application [4]. ...
Background
Premenstrual syndrome (PMS) is a prevalent gynecological disease and is significantly associated with abnormal neural activity. Acupuncture is an effective treatment on PMS in clinical practice. However, few studies have been performed to investigate whether acupuncture might modulate the abnormal neural activity in patients with PMS. Thereby, the aim of the study was to assess alterations of the brain activity induced by acupuncture stimulation in PMS patients.
Methods
Twenty PMS patients were enrolled in this study. All patients received a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) scan before and after electro-acupuncturing stimulation (EAS) at Sanyinjiao (SP6) acupoint in the late luteal phase of menstrual. Fractional amplitude of low-frequency fluctuation (fALFF) method was applied to examine the EAS-related brain changes in PMS patients.
Results
Compared with pre-EAS at SP6, increased fALFF value in several brain regions induced by SP6, including brainstem, right thalamus, bilateral insula, right paracentral lobule, bilateral cerebellum, meanwhile, decreased fALFF in the left cuneus, right precuneus, left inferior temporal cortex.
Conclusions
Our findings provide imaging evidence to support that SP6-related acupuncture stimulation may modulate the neural activity in patients with PMS. This study may partly interpret the neural mechanisms of acupuncture at SP6 which is used to treat PMS patients in clinical.
Trial registration : The study was registered on http://www.chictr.org.cn . The Clinical Trial Registration Number is ChiCTR-OPC-15005918, registry in 29/01/2015.
... Despite these oscillations, it generally does not constitute premenstrual dysphoric disorder (PMDD), which can induce MDD-like impairments (Reid and Soares 2018). PMDD would begin after the ovulatory phase, ending shortly after menstruation, and causing impairment in one's daily functioning and relationships (American Psychiatric Association 2013). ...
This study aimed to systematically review the relationship of obesity-depression in the female sex. We carried out a systematic search (PubMed, MEDLINE, Embase) to quantify the articles (controlled trials and randomized controlled trials) regarding obesity and depression on a female population or a mixed sample. Successively, we established whether the sex specificities were studied by the authors and if they reported on collecting data regarding factors that may contribute to the evolution of obesity and depression and that could be responsible for the greater susceptibility of females to those conditions. After applying the inclusion and exclusion criteria, we found a total of 20 articles with a female sample and 54 articles with a mixed sample. More than half of all articles (51.35%, n = 38) evaluated the relationship between depression and obesity, but only 20 (27.03%) evaluated this relationship among females; still, 80% of those (n = 16) presented supporting results. However, few articles considered confounding factors related to female hormones (12.16%, n = 9) and none of the articles focused on factors responsible for the binomial obesity-depression in the female sex. The resulting articles also supported that depression (and related impairments) influencing obesity (and related impairments) is a two-way road. This systematic review supports the concurrency of obesity-depression in females but also shows how sex specificities are ultimately under-investigated. Female sex specificity is not being actively considered when studying the binomial obesity-depression, even within a female sample. Future studies should focus on trying to understand how the female sex and normal hormonal variations influence these conditions.
... Pharmacologic intervention for PMS includes hormone therapy and symptomatic treatment, including progesterone, oryzanol, vitamins, and oral antianxiety antidepressants [3]. Even though it works very well, evidence on the efficacy of sustained progesterone and the side effects of antidepressant and anxiolytics limited further application [4]. ...
Background: Premenstrual Syndrome(PMS) is a prevalent gynecological disease and is significantly associated with abnormal neural activity. Acupuncture is an effective treatment on PMS in clinical practice. However, few studies have been performed to investigate whether acupuncture might modulate the abnormal neural activity in patients with PMS. Thereby, the aim of the study was to assess alterations of the brain activity induced by acupuncture stimulation in PMS patients.
Methods: 20 PMS patients were enrolled in this study. All patients received a 6-min resting-state functional magnetic resonance imaging(rs-fMRI) scan before and after electro-acupuncturing stimulation (EAS) at Sanyinjiao (SP6) acupoint in the late luteal phase of menstrual. Applied the fractional amplitude of low frequency fluctuation(fALFF) method to examine EAS-related brain changes in PMS patients.
Results: Compared with pre-EAS at SP6, increased fALFF value in several brain regions induced by SP6, including brainstem, right thalamus, bilateral insula, right paracentral lobule, bilateral cerebellum, meanwhile, decreased fALFF in the left cuneus, right precuneus, left inferior temporal cortex.
Conclusions: Our findings provide imaging evidence to support that SP6-related acupuncture stimulation may modulate the neural activity in patients with PMS. This study may partly interpret the neural mechanisms of acupuncture at SP6 which is used to treat PMS patients in clinical.
Trial registration:The study was registered on http://www.chictr.org.cn, the Clinical Trial Registration Number is ChiCTR-OPC-15005918, registry in 29/01/2015.
... 8,9 Although the symptoms and treatment modalities for PMS have been investigated, 1,10-13 the PMS etiology remains unclear. 14,15 Fine-particulate air pollutants can considerably affect the reproductive health of women via the sex hormone axis and cause symptoms, such as ovarian failure, endometriosis, dysregulated menstruation and reduced fertility and pregnancy viability. [16][17][18][19] Because PMS may also be associated with sex hormone axis dysregulation, 20 investigating the direct association between air pollutant concentrations and PMS is critical. ...
Objective:
Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk.
Population:
We combined data from the Taiwan Air Quality-Monitoring Database (TAQMD) and the Longitudinal Health Insurance Database. In total, an observational cohort of 85078 Taiwanese women not diagnosed as having PMS.
Methods:
Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants.Main Outcome Measures: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type.
Results:
Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤ 2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04).
Conclusions:
High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2, and PM2.5.
... SSRI dosages used to treat PMDD are lower than what is commonly prescribed for depression, suggesting different underlying biological mechanisms between PMDD and depression. Recommended dosages for the SSRIs in treating severe premenstrual disorders are as follows: paroxetine 5-25 mg/day, fluoxetine 10-20 mg daily, sertraline 50-100 mg daily, citalopram 10-20 mg daily and escitalopram 10-20 mg/day (130). Other antidepressants that do not target serotonin functioning are less effective than SSRIs, further supporting that serotoninergic dysfunction is involved in PMDD. ...
Premenstrual syndrome (PMS) or the more severe and debilitating form premenstrual dysphoric disorder (PMDD) affects a large proportion of menstruating women. PMS and PMDD are associated with a cyclical recurrence of mood and behavioural and physical symptoms in the late luteal menstrual phase, which significantly interferes with a woman’s physical and psychological well-being. The aetiology of these disorders is unclear, but research suggests involvement of altered neurotransmitter systems and increased sensitivity to gonadal hormone fluctuations. Due to the complexity of the disorder, there is no single treatment that is successful for all women; however, various treatments aimed at regulating neurotransmitter systems and suppressing gonadal steroids have been efficacious. This chapter will provide an updated review on diagnosis, prevalence, morbidity, risk factors, and evidence-based treatments that have been effective in treating the symptoms of PMDD.
... In those subjects affected by PMDD without psychiatric comorbid condition, selective serotonin reuptake inhibitor antidepressants and low doses of combined contraceptives (oral estroprogestins) are considered firstline pharmacological treatments. 9,41,42 On the other hand, the presence of a comorbid BD brings out an important safety consideration regarding the use of SSRI and the consequence risk of mood switches. 43,44 Aim of the present study was therefore to provide a review of the relevant literature on comorbid BD-PMDD and a set of hypotheses to test going forward in RCT studies, in order to manage these complex cases in the most complete and personalized manner. ...
Bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) are two cyclic mood illnesses, sometimes presenting together. Their comorbidity appears to be linked to common biological mechanisms and usually results in more severity of mood symptoms and a poorer long-term outcome. Nevertheless, the management of comorbid PMDD/BD has been scarcely studied. Therefore, the aim of the present paper was to review the published literature on the treatment of comorbid PMDD/BD and to provide point-by-point hypotheses to address these complex clinical cases. We searched PubMed to identify the studies focused on the treatment and management of comorbid PMDD/BD using the following search words, alone and in combination: premenstrual dysphoric disorder, bipolar disorder, comorbid, treatment, management, pharmacotherapy, psychotherapy. The search was conducted on the 1st of June 2019 and yielded 55 records. Four papers met our inclusion/exclusion criteria and were therefore included in our qualitative synthesis. Integrating the few data pertaining to the treatment of comorbid PMDD/BD with the large amount of published data on the two conditions separately, we can suggest that the management of comorbid PMDD/BD needs as a first step to stabilize the bipolar symptoms by means of optimal dosages of mood stabilizers. Then, in euthymic BD patients, the PMDD symptoms could be treated with estroprogestins (first-line treatment). On the contrary, during acute phases of BD, antidepressants (for major depressive episodes) and atypical antipsychotics/hormonal modulators (for manic episodes) could be considered as promising add-on treatments to mood stabilizers. In case of resistant PMDD/BD symptoms, combined strategies should be taken into account, as well as alternative treatments, such as lifestyle changes. In conclusion, RCTs on comorbid PMDD/BD are still lacking. The management of this complex condition is therefore challenging and it requires a tailored treatment.
... Presently, pharmacologic intervention for PMS includes hormone therapy and symptomatic treatment, using progesterone, oryzanol, vitamins, and oral antianxiety antidepressants [3]. Due to limited evidence on the efficacy of sustained progesterone [4] and the side effects of antidepressant and anxiolytics, in some cases, alternative therapies are recommended for patients with PMD. Acupuncture is one of the most commonly used therapies. ...
Background:
Premenstrual syndrome (PMS) is one of the most common gynecological conditions with no standard modern therapeutic schedule. Some studies have reported the effects of acupuncture in treating PMS, but the intervention time varies. This review evaluated the efficacy of acupuncture for patients with PMS and the appropriate time to initiate acupuncture therapy. The review has been registered on the "PROSPERO" website; the registration number is CRD42018109724.
Methods:
A comprehensive literature search was performed on 9 electronic databases from the time of inception to September 2018. RCTs studies on acupuncture for PMS compared with medication, sham acupuncture, or no treatment were included. Statistical analysis and investigation of heterogeneity source were carried out using RevMan5. 3.
Results:
A total of 15 studies, comprising of 1103 cases, were included. Overall, acupuncture significantly increased the effective rate of PMS compared with medicine and sham acupuncture. Subgroup analyses showed no significant difference among different intervention time to start acupuncture treatment. Among the acupoints involved in the treatment of PMS, SP6, LR3, and RN4 were the most commonly used.
Conclusions:
The current meta-analysis reveals that acupuncture leads to better effective rate, but the intervention time has no significant effect on the efficacy of acupuncture treatment for PMS. SP6, LR3, and RN4 are the most commonly used acupoints in treating PMS. However, large-scale, case-control studies with rigorous designs are required to provide more accurate evidence.
... SSRIs are the first choice in non-hormonal therapies and their use increases serotonin activity in the brain to improve PMS (4,12,15,31). Indeed, studies show that SSRIs are effective in PMS management compared to placebo (5,16,31,32). However, some of the drugs in this group may have quite a lot of side effects (4). ...
Premenstrual syndrome (PMS) is a health problem that occurs with physical and psychological symptoms presenting about five days before menstruation, end within a few days after the onset of menstruation. The most common symptoms are appetite changes, edema, breast tenderness, abdominal pain, back pain, headache, fatigue, insomnia, depressive affect, irritability, angry outbursts andanxiety. Most women’s half of lifes go through with premenstrual problems and quality of life is affected negatively. PMS prevalence is notably high in the world and in our country. In this respect, it is important to increase awareness of health professionals and women about PMS. The aim of this review is to explain current approaches of PMS management in the context of international guidelines. Getting detailed anamnesis for the diagnosis of PMS, if necessary, consultations and laboratory investigations are carried out. In addition, the diagnosis of PMS is confirmed by assessing women’s symptom records for at least two months showing the type of symptoms and the time of appearance of these symptoms in the menstrual cycle. PMS management is carried out gradually by multidisciplinary team that adopted an integrative holistic approach in the direction of individualized plan. The first step includes creating awareness about PMS, teaching to women self-screening, lifestyle changes, regulation of diet, methods of coping with stress. In the second step, cognitive behavioral therapy and complementary alternative therapies are implemented. If the problem continues, there is pharmacological treatment in the third step. Finally, surgical treatment is applied in the fourth step.
... Одним из кандидатов на роль патогенетического фактора ПМС является нейростероид аллопрегненолон -нейроактивный метаболит прогестерона, стимулирующий рецепторы ГАМК в головном мозге и, следовательно, определяющий поведенческие реакции, ответ на стрессовое воздействие, изменения настроения, а также наступление сна. Содержание аллопрегненолона в периферической крови больных ПМС снижено по сравнению с таковым у здоровых женщин, особенно в лютеиновую фазу цикла [19]. ...
... SSRIs are the first choice in non-hormonal therapies and their use increases serotonin activity in the brain to improve PMS (4,12,15,31). Indeed, studies show that SSRIs are effective in PMS management compared to placebo (5,16,31,32). However, some of the drugs in this group may have quite a lot of side effects (4). ...
The spectrum of premenstrual disorders is related to hormonal changes in the menstrual cycle and are experienced by nearly 40% of women. Approximately 3–8% of women are affected by severe premenstrual syndrome, including premenstrual dysphoric disorder (PMDD); a chronic, debilitating disorder with severe emotional and physical symptoms and functional impairment. PMDD significantly affects women's quality of life; recent evidence suggests that 86% of patients have considered suicide, with 30% having attempted suicide at least once. In 2019, PMDD was added to the International Statistical Classification of Diseases and Related Health Problems, (ICD–11), which validates PMDD as a legitimate diagnosis and acknowledges growing scientific and medical understanding of this previously under recognised condition. Symptom relief can often be achieved through medical management, therefore it is important to increase awareness among healthcare professionals at all levels. To understand the pathophysiology, diagnosis and treatment options for premenstrual disorders, including PMDD. To know the different classifications of premenstrual disorders, including DSM‐5 and World Health Organization (WHO) ICD‐11 classifications of PMDD. To understand the potential benefits associated with multidisciplinary care for women with premenstrual disorders like PMDD. Should women with severe premenstrual syndrome be classified under mental health disorders in the ICD classification?
This case report discusses the case of a 28-year-old woman, with a history of Premenstrual Dysphoric Disorder, who presented with polymorphic psychosis, with catatonic features, which started a week prior to menstruation. She was treated with lorazepam and olanzapine and her psychotic symptoms resolved rapidly, upon menstruation. She was subsequently treated in the community and continues to do well without antipsychotic therapy. Not recognised in either ICD or DSM criteria, menstrual psychosis is nonetheless well described in the literature. Menstrual psychosis with catatonia appears to be an extremely rare condition and, as such, its pathology and most appropriate treatment is not well described.
Around 80% of women worldwide suffer mild Premenstrual Disorders (PMD) during their reproductive life, while up to a quarter are affected by moderate to severe symptoms, and between 3% to 8% experience a severe form. It is classified as premenstrual syndrome (PMS) with predominantly physical symptoms and premenstrual dysphoric disorder (PMDD) with psychiatric symptoms. The present review analyzes the factors associated with PMD and the Hypothalamus-Pituitary-Ovarian or Hypothalamus-Pituitary-adrenal axis and discusses the main animal models used to study PMDD. Evidence shows that the ovarian hormones participate in PMDD symptoms, and several points of regulation of their synthesis, metabolism, and target sites could be altered. PMDD is complex and implies several factors that require consideration when this condition is modeled in animals. Of particular interest are those points related to areas that may represent opportunities to develop new approximations to understand the mechanisms involved in PMDD and possible treatments.
IntroductionHeadache is a common symptom among women, including during the menstrual cycle. The migraine frequency in women who present migraine associated with the menstrual period ranges from 50% to 70%. Premenstrual syndrome (PMS) is prevalent among women, affecting 80% to 90% of them throughout their lives.Objective
The objectives of this study were to verify PMS prevalence and its characteristics among women who present with cephalalgia in the neurology ambulatory care unit and show the prevalence of headache and its association with PMS in the gynecology ambulatory care unit.Methods
It is a descriptive and qualitative study which was carried out at Emilio Carlos Teaching Hospital in the neurology and gynecology ambulatory care units with women aged 18 to 52 years old. Eighty-seven questionnaires were distributed and self-applied throughout the year of 2018 for data collection. Each questionnaire consisted of 27 questions about the life cycle of the women and their headache episodes. The diagnostic criteria for headache and migraine from the International Headache Society were used. Criteria for PMS were met according to the quality of life questionnaire.ResultsIn gynecology unit group, 9% of the women did not present headache, 76% had PMS and 94% presented with headache during PMS. In neurology, 79% of the women had PMS and 79% of the women who presented with cephalalgia also had PMS.Conclusion
There is a large percentage of PMS in both groups, i.e. neurological unit and gynecological unit, showing it is not a spurious correlation.
Serotonin (5-hydroxytryptamine or 5-HT) is a mediator with primary functions, both in the central nervous system and digestive system. At the digestive level, about 90% of 5-HT is localized in enterochromaffin cells, and about 10% in enteric neurons. In the gastrointestinal tract, 5-HT affects motor, secretory, and sensory functions via activation of seven subclasses of receptors, which differ on the basis of structure, function, and signaling mechanisms. The 5-HT transporter, deputed specifically to 5-HT reuptake, plays also an important role in the modulation of serotonergic pathways. There is increasing evidence that the serotonergic system is involved in the pathogenic mechanisms of gastrointestinal diseases, with particular regard for functional gastrointestinal disorders, and the pathophysiology of some frequently associated psychiatric and psychological comorbidities. The constant bidirectional interplay between brain and gut (brain-gut axis), in which 5-HT is deeply involved, can account for the multifaceted central and peripheral actions of this mediator. In this context, the role of the intestinal microbiota, with its ability of both producing 5-HT and being modulated by 5-HT, represents a field of high interest deserving preclinical and clinical investigations.
Purpose of Review
In contrast to premenstrual dysphoric disorder (PMDD), premenstrual exacerbations (PMEs) of ongoing mood disorders are understudied. The aim of this review is to describe diagnostic issues, epidemiology, underlying mechanisms, and treatment for PME in unipolar depression and bipolar disorder, and to discuss clinical and research implications.
Recent Findings
Community-based and clinical studies estimate that in women with mood disorders around 60% report PME, while some women with bipolar disorder also show symptom exacerbations around ovulation. In general, PME predicts a more severe illness course and an increased burden. While heightened sensitivity to fluctuations of sex hormone levels across the menstrual cycle appears to contribute to PME and PMDD, the overlap of their underlying biological mechanisms remains unclear. Beneficial treatments for PMDD show less or no efficacy in PME. Pharmacological treatments for PME in mood disorders predominantly seem to profit from adjustable augmentation of treatment dosages during the luteal phase for the underlying disorder. However, the evidence is sparse and mainly based on earlier small studies and case reports.
Summary
Previous research is mainly limited by the lack of a clear differentiation between PME and PMDD comorbidity with mood disorders. More systematic research with uniformly defined and prospectively assessed subgroups of PME in larger epidemiological and clinical samples is needed to receive reliable prevalence estimates and information on the clinical impact of PME of mood disorders, and to uncover underlying mechanisms. In addition, larger randomized controlled trials are warranted to identify efficacious pharmacological and psychotherapeutic treatments for affected women.
Premenstrual syndrome (PMS), including the severe subtype premenstrual dysphoric disorder (PMDD), DSM-5 category, represents a challenging combination of hormonal, environmental and neuroendocrine dysfunctions with menstrual cycle-related pattern. Controversies around the role of daily stress and associated anomalies of hypothalamic-pituitary-adrenal axis are related to the fact that stress is all the time, not just a fluctuating element. This is a narrative review on PMS/PMDD and cortisol profile. 46 articles are cited (between 2009 and 2020). PMD/PMDD underlines multiple imbalances and anomalies of the cortisol levels or its secretory pattern may be a few of them, despite the fact that multiple controversies are still present and most of studies are of limited statistical power. Women with PMS may have higher levels of cortisol in relationship to stress independently of the cycle phase, also a delay of CAR (cortisol awakening response) peak and a delayed cortisol slope during day time. It does not seem that CAR pattern is related to the phases of menstrual cycle. CAR anomalies may be associated with pain perception disturbances in PMS females. The most modern area of interest is related to allopregnanolone, a progesterone metabolite with neuroactive profile. The diurnal serum baseline cortisol and the values of cortisol after dexamethasone suppression test may be similar between patients with PMS and without, but the females with PMS that have higher allopregnanolone associate blunted values of cortisol during the night versus control (without PMS) and versus women with low allopregnanolone levels, thus proving a suboptimal response to stress. Allopregnanolone modules GABA receptors on a paradoxical manner inducing anxiety and irritability during luteal phase on women with a specific predisposal configuration of GABA receptor as those confirmed with PMDD. Overall, PMS/PMDD impairs the quality of life, thus the more we understand about its pathogeny, the easier it gets to control it.
Women’s body dissatisfaction and shame has been found to increase in the premenstrual phase of the cycle and to be associated with premenstrual distress. However, the factors involved remain little understood. In the present study, 116 women completed an online survey including standardized measures of premenstrual distress, body shame, menstrual shame, and self-objectification, and open-ended questions about premenstrual embodiment. Eight participants completed a semi-structured interview. Significant positive correlations were found between premenstrual distress, body shame, and menstrual shame. Self-objectification was significantly negatively correlated with body shame. Thematic analysis identified internalization and resistance of unrealistic cultural constructions of feminine beauty, concealment of the body, and reduced engagement in body-management behaviors. The implications of the findings for understanding women’s premenstrual distress and embodiment are discussed.
Objective:
Premenstrual syndrome (PMS) affects 20%-30% of women but current medical treatments are limited in their efficacy. The objective of this study was to compare efficacy of a broad-spectrum micronutrient formula (consisting mainly of minerals and vitamins) to a single vitamin (B6) for treatment of PMS, for which B6 has already been shown to be efficacious.
Methods:
This double-blind, randomized, treatment-controlled trial allocated 78 (72 completed) regularly menstruating women with PMS to consume micronutrients or vitamin B6 (80 mg/day) daily following a two-cycle baseline period, for three menstrual cycles. The primary outcome measure, Daily Record of Severity of Problems (DRSP), established PMS as well as tracked change in five PMS symptoms: psychological, somatic, total symptoms, impact ratings, and worst day ratings.
Results:
Linear-mixed model analyses indicated both treatments produced comparable reduction in PMS symptoms with medium effect sizes (ES) across all PMS variables as measured by the DRSP (micronutrient ES = 0.50-0.56; B6 ES = 0.43-0.56), with 72% of the micronutrient and 60% of the vitamin B6 group identified as in full remission in PMS symptoms after three cycles. The micronutrient-treated participants showed greater improvement than the B6 group (between group d = 0.51, p < 0.05) in health-related quality of life. For those women (n = 28) who met criteria for premenstrual dysphoric disorder (PMDD), the DRSP ES were larger for those who had been in the micronutrient condition (ES = 1.28-1.67) as compared with those on B6 (ES = 0.50-0.75), although the group differences were not statistically reliable. There were no group differences in side effects, nor any serious adverse effects reported.
Conclusions:
Both treatments provided similar benefit for reducing PMS symptoms, with greater effect of micronutrients on quality of life as well as potential clinical benefit of micronutrients for PMDD. This study provides further efficacy data on B6 and also identifies the nutritionally broader spectrum intervention as possibly having specific advantages for those whose symptoms are more severe. As this is the first study to investigate these treatments for PMDD, systematic replication is required.
The major criticisms made to the conceptualization of PMDD as a clinical syndrome focus on pathologizing of women’s biology and its consequent medicalization which perpetuated misconceptions related to menses. This is a reality in History of Medicine. The excessive medicalization of the menstrual experience that interferes in life is very important in Western countries. Premenstrual syndrome (PMS) is a health problem that affects millions of women of reproductive age and, in some cases, may be severe enough to be considered as a premenstrual dysphoric disorder (PMDD). Both, PMS and PMDD, are composed by affective, behavioural, and physical symptoms. Risk factors identified, which predispose to PMS/PMDD, are the age between 25 and 35 years, to have a psychiatric history, family history of PMDD, unhealthy living habits, and the apparition of stressful life events. In addition to that, it has been established a comorbidity of PMDD with various psychiatric disorders as major depression and anxiety disorders. The first-line treatment for PMDD is pharmacological with SSRIs. From the medical point of view, there is some evidence of the efficacy of non-pharmacological treatments such as relaxation and aerobic and cognitive behavioural therapy that are used mostly in mild cases. Some authors remind us the historical and negative conceptions about the female body plus a reproductivist vision, as the cause of many women’s behaviour, have had a determinate influence in the consideration about women’s experience as diseases. In our opinion, we consider it is important to rethink about it and talk about premenstrual experience instead of syndrome. It could be used to reinforce and maintain the patriarchal model. If women are treated medically because of their own biology, they would respond again to the female stereotype of women as mild, placid, and undemanding. At the same time, for some women could represent an attractive explanation to justify their oppression and their relative lack of success compared to men. This means that women can attribute their subordination and oppression to something identifiable and potentially curable, rather than attributing to gender power relations. Finally, the concept clearly benefits to the pharmaceutical industry, as the medicalization of premenstrual experiences increased their market.
Context:
Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAAreceptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.
Objective:
The objective was to test whether inhibition of allopregnanolone by treatment with the GABAAmodulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.
Design:
This was an explorative randomized, double-blind, placebo-controlled study.
Setting:
Swedish multicentre study with 10 centers.
Participants:
Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm.
Intervention:
Subjects were randomized to treatment with UC1010 (10 or 16mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.
Outcome measures:
The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).
Results:
26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p=0.041) and borderline significance (p=0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n=60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p=0.006), and for sum of Negative mood score (p=0.003) and impairment (p=0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.
Conclusions:
This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.
Clinical evidence suggests that mood and behavioral symptoms in premenstrual dysphoric disorder (PMDD), a common, recently recognized, psychiatric condition among women, reflect abnormal responsivity to ovarian steroids. This differential sensitivity could be due to an unrecognized aspect of hormonal signaling or a difference in cellular response. In this study, lymphoblastoid cell line cultures (LCLs) from women with PMDD and asymptomatic controls were compared via whole-transcriptome sequencing (RNA-seq) during untreated (ovarian steroid-free) conditions and following hormone treatment. The women with PMDD manifested ovarian steroid-triggered behavioral sensitivity during a hormone suppression and addback clinical trial, and controls did not, leading us to hypothesize that women with PMDD might differ in their cellular response to ovarian steroids. In untreated LCLs, our results overall suggest a divergence between mRNA (for example, gene transcription) and protein (for example, RNA translation in proteins) for the same genes. Pathway analysis of the LCL transcriptome revealed, among others, over-expression of ESC/E(Z) complex genes (an ovarian steroid-regulated gene silencing complex) in untreated LCLs from women with PMDD, with more than half of these genes over-expressed as compared with the controls, and with significant effects for MTF2, PHF19 and SIRT1 (P<0.05). RNA and protein expression of the 13 ESC/E(Z) complex genes were individually quantitated. This pattern of increased ESC/E(Z) mRNA expression was confirmed in a larger cohort by qRT-PCR. In contrast, protein expression of ESC/E(Z) genes was decreased in untreated PMDD LCLs with MTF2, PHF19 and SIRT1 all significantly decreased (P<0.05). Finally, mRNA expression of several ESC/E(Z) complex genes were increased by progesterone in controls only, and decreased by estradiol in PMDD LCLs. These findings demonstrate that LCLs from women with PMDD manifest a cellular difference in ESC/E(Z) complex function both in the untreated condition and in response to ovarian hormones. Dysregulation of ESC/E(Z) complex function could contribute to PMDD.
Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive-affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets.
Background- Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Methods- Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double blind placebo or dutasteride (low-dose 0.5 mg/day in the first 8 PMDD and 8 control women or high-dose 2.5 mg/day in the second group of women). All women completed the Daily Rating Form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. Results- In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Conclusions- Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data provide preliminary support for the pathophysiologic relevance of neurosteroids in this condition.Neuropsychopharmacology accepted article preview online, 14 August 2015. doi:10.1038/npp.2015.246.
The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.
Premenstrual dysphoric disorder, which affects 2%–5% of premenopausal women, was included in Appendix B of DSMIV, "Criterion Sets and Axes Provided for Further Study." Since then, aided by the inclusion of specific and rigorous criteria in DSM-IV, there has been an explosion of research on the epidemiology, phenomenology, pathogenesis, and treatment of the disorder. In 2009, the Mood Disorders Work Group for DSM-5 convened a group of experts to examine the literature on premenstrual dysphoric disorder and provide recommendations regarding the appropriate criteria and placement for the disorder in DSM-5. Based on thorough review and lengthy discussion, the work group proposed that the information on the diagnosis, treatment, and validation of the disorder has matured sufficiently for it to qualify as a full category in DSM-5. A move to the position of category, rather than a criterion set in need of further study, will provide greater legitimacy for the disorder and encourage the growth of evidence-based research, ultimately leading to new treatments.
Premenstrual disorders (PMD) are characterised by a cluster of somatic and psychological symptoms of varying severity that
occur during the luteal phase of the menstrual cycle and resolve during menses (Freeman and Sondheimer, Prim Care Companion
J Clin Psychiatry 5:30–39, 2003; Halbreich, Gynecol Endocrinol 19:320–334, 2004). Although PMD have been widely recognised for many decades, their precise cause is still unknown and there are no definitive,
universally accepted diagnostic criteria. To consider this issue, an international multidisciplinary group of experts met
at a face-to-face consensus meeting to review current definitions and diagnostic criteria for PMD. This was followed by extensive
correspondence. The consensus group formally became established as the International Society for Premenstrual Disorders (ISPMD).
The inaugural meeting of the ISPMD was held in Montreal in September 2008. The primary aim was to provide a unified approach
for the diagnostic criteria of PMD, their quantification and guidelines on clinical trial design. This report summarises their
recommendations. It is hoped that the criteria proposed here will inform discussions of the next edition of the World Health
Organisation’s International Classification of Diseases (ICD-11), and the American Psychiatric Association’s Diagnostic and
Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria that are currently under consideration. It is also
hoped that the proposed definitions and guidelines could be used by all clinicians and investigators to provide a consistent
approach to the diagnosis and treatment of PMD and to aid scientific and clinical research in this field.
KeywordsPMS–PMDD–Premenstrual disorder–Diagnostic criteria–Quantification–Trial design–International consensus
Premenstrual mood disorders afflict a substantial number of women of reproductive age. Medical treatments provide excellent symptomatic relief to many women but at times a poor therapeutic response or adverse effects attributable to these therapies lead women to seek alternative solutions. Oophorectomy (with concomitant hysterectomy) followed by low-dose estrogen therapy has been shown to be an effective alternative for such cases of menstrual-cycle-related mood disorder.
Premenstrual syndrome (PMS) is a condition of cyclical and recurrent physical and psychological discomfort occurring 1 to 2 weeks before menstrual period. More severe psychological symptoms have been described for the premenstrual dysphoric disorder (PMDD). No single treatment is universally recognised as effective and many patients often turn to therapeutic approaches outside of conventional medicine. This systematic review is aimed at analysing the effects of herb remedies in the above conditions. Systematic literature searches were performed in electronic databases, covering the period January 1980 to September 2010. Randomised controlled clinical trials (RCTs) were included. Papers quality was evaluated with the Jadad' scale. A further evaluation of PMS/PMDD diagnostic criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10 of them were included. The heterogeneity of population included, study design and outcome presentation refrained from a meta-analysis. Vitex agnus castus was the more investigated remedy (four trials, about 500 women), and it was reported to consistently ameliorate PMS better than placebo. Single trials also support the use of either Gingko biloba or Crocus sativus. On the contrary, neither evening primrose oil nor St. John's Wort show an effect different than placebo. None of the herbs was associated with major health risks, although the reduced number of tested patients does not allow definitive conclusions on safety. Some herb remedies seem useful for the treatment of PMS. However, more RCTs are required to account for the heterogeneity of the syndrome.
It seems that during the past decade we have been witnessing an evolution of a consensus on the phenomenology and time course of various types of MRDs. We are in a stage in which definitions and diagnostic criteria can be developed, but their broad acceptance is still not assured. The etiology and pathophysiology are still fiercely debated, but reasonable and feasible methods for scientific elucidation of the various hypotheses are in place and are followed by solid groups. Despite the uncertainty concerning the etiology of MRDs, reasonably efficient treatment modalities do exist, and most sufferers of MRDs should expect an eventual alleviation of their symptoms if they are treated in a specialized, established, and up-to-date program.
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.
Objectives:
Premenstrual dysphoric disorder (PMDD) is a disabling condition affecting approximately 2% to 8% of women during reproductive age. It has been recently included in the mood disorder section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, but its treatment as a primary psychiatric illness is still debated, because of the high prevalence of other mental disturbances in PMDD patients. On the other hand, clear clinical guidelines for PMDD patients not suffering from comorbid mental conditions are not yet available. The aim of the present study was therefore to systematically review the original articles pertaining to the treatment of PMDD in adult women free of any current or previous psychiatric comorbidity.
Methods:
We searched PubMed to identify published studies on PMDD, including randomized controlled trials, open-label trials, and case series or case reports involving adult women with no history of comorbid mental conditions. The search was conducted in April 2015.
Results:
We found 55 studies fulfilling our inclusion criteria, 49 of them focused on pharmacological/chemical agents and the remaining 6 on nonpharmacological interventions.
Conclusions:
Based on the results of our qualitative synthesis, the best therapeutic option in the treatment of adult PMDD patients free of other mental disorders are selective serotonin reuptake inhibitor antidepressants (especially paroxetine and fluoxetine) and low doses of oral estroprogestins. Other interventions, such as light therapy, cognitive behavioral therapy, food supplements, and herbal medicines, showed promising effects, but other investigations are needed to confirm their efficacy.
My attention has been increasingly directed to a large group of women who are handicapped by premenstrual disturbances of manifold nature. It is well known that normal women suffer varying degrees of discomfort preceding the onset of menstruation. Employers of labor take cognizance of this fact and make provision for the temporary care of their employees. These minor disturbances include increased fatigability, irritability, lack of concentration and attacks of pain.
In another group of patients, the symptoms complained of are of sufficient gravity to require rest in bed for one or two days. In this group, particularly, pain plays the predominant rôle. There is still another class of patients in whom grave systemic disorders manifest themselves predominantly during the premenstrual period.
REPORT OF CASES
Case 1. —A young, unmarried woman suffered from frequent convulsive attacks, which later occurred exclusively within ten days preceding menstruation. Neurologic investigation resulted in a diagnosis
In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome.
Males and females differ in their predisposition to certain clinical disorders. One of the most widely documented findings in psychiatric epidemiology is that women have higher rates of major depressive episodes than men, a phenomenon observed worldwide using a variety of diagnostic schemes and interview methods.1,2 The prevalence of depression among women in these studies was reported to be between 1.5 and 3 times that of men. Although a genetic predisposition to major depression has been extensively postulated, the actual mechanisms involved in this disorder are still being investigated. Several authors have reported similarities and associations between the symptoms of affective disorders such as anxiety, panic disorder, major depression, and seasonal affective disorder, and premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD).3-8 It has also been noted that the incidence of anxiety, mood disorders, and depression among women suffering with PMS is greater than that of the general population.9-11 Evidence supporting the view that a genetically determined vulnerability plays a major role in the expression of PMS/PMDD is derived from twin and family studies,12-15 that showed a high correlation between mothers and daughters and also between mono-and dizygotic twins. Additionally, a similarity of PMS subtypes was noted between mothers and daughters. Thus, genetic factors have been implicated repeatedly in the pathogenesis of PMS/PMDD, although no specific susceptibility gene has been identified.
Female-specific psychiatric illness including premenstrual dysphoria, perinatal depression, and psychopathology related to the perimenopausal period are often underdiagnosed and treated. These conditions can negatively affect the quality of life for women and their families. The development of screening tools has helped guide our understanding of these conditions. There is a wide disparity in the methods, definitions, and tools used in studies relevant to female-specific psychiatric illness. As a result, there is no consensus on one tool that is most appropriate for use in a research or clinical setting. In reviewing this topic, we hope to highlight the evolution of various tools as they have built on preexisting instruments and to identify the psychometric properties and clinical applicability of available tools. It would be valuable for researchers to reach a consensus on a core set of screening instruments specific to female psychopathology to gain consistency within and between clinical settings.
Objective:
This phase 3 study evaluated the endometrial safety of bazedoxifene (BZA)/conjugated estrogens (CE) and bone mineral density (BMD) effects vs BZA alone, hormone therapy, and placebo (PBO).
Methods:
The Selective estrogens, Menopause, And Response to Therapy (SMART)-5 trial was a multicenter, randomized, double-blind, PBO- and active-controlled study in postmenopausal women with an intact uterus (N = 1843; aged 40-65 years) seeking treatment for menopausal symptoms. Subjects received daily oral BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO. Primary endpoints were incidence of endometrial hyperplasia and percent change in lumbar spine BMD at 12 months. Secondary endpoints included additional osteoporosis parameters and assessments of tolerability and safety.
Results:
At 12 months, endometrial hyperplasia incidence was low (<1%) and similar among groups. The BZA/CE group showed significantly greater increases in lumbar spine and total hip BMD vs decreases with PBO (P < .001); the CE/MPA group had increased lumbar spine BMD compared with that in the BZA/CE group. The BZA 20 mg/CE 0.45 and 0.625 mg groups had cumulative amenorrhea rates similar to those with PBO and BZA and significantly higher than those with CE 0.45 mg/MPA 1.5 mg (P < .001). The incidence of breast tenderness with BZA/CE was similar to that with PBO and BZA and significantly lower than with that with CE/MPA (P < .01). Although adverse event (AE) rates were similar among the groups, the incidence of serious AEs overall and AE-related discontinuation rates were higher with CE/MPA than with BZA/CE, BZA, or PBO.
Conclusions:
BZA/CE showed low rates of endometrial hyperplasia and improved lumbar spine and total hip BMD and was generally safe and well tolerated.
The decision to retain or remove the ovaries and cervix at the time of hysterectomy is complex and controversial. We present a summary of the current literature on the risks and benefits of elective oophorectomy and subtotal hysterectomy to inform surgical decision making. There are no randomized trials of oophorectomy compared with hysterectomy and ovarian preservation. Observational studies have conflicting evidence on long-term health outcomes following oophorectomy. In contrast, there are high-quality randomized trials of subtotal versus total hysterectomy; there is a decrease in some short-term surgical complications for women who undergo subtotal hysterectomy, but no differences in long-term outcomes.
Inclusion of premenstrual dysphoric disorder (PMDD) into the main text of the DSM has been a point of controversy for many years. The purpose of this article is to address the main concerns raised by opponents to its inclusion. Concerns are presented and countered in turn.
To identify the most prevalent arguments against inclusion of PMDD, we searched MEDLINE (1966-2012), PsycINFO (1930-2012), the Internet, and reference lists of identified articles during September 1-17, 2012, using the keywords PMDD, premenstrual syndrome (PMS), DSM, DSM-5, concerns, controversy, women, political power, workforce, courts, and history. The search was restricted to English-language publications. A total of 55 articles were identified and included. The most pressing arguments against inclusion were grouped by similarity and addressed if they were reported 5 or more times. Our review of the sources yielded 38 concerns regarding PMDD; 6 concerns were reported at least 5 times and are addressed in this article.
Evidence culled from historical and legal trends does not support the alleged societal use of PMS to harm women (eg, keeping women out of the workforce or using PMS against women in child custody disputes). Further, current epidemiologic research has answered all of the methodology criticisms of opponents. Studies have confirmed the existence of PMDD worldwide. The involvement of pharmaceutical companies in research has been questioned. However, irrespective of the level of association with industry, current research on PMDD has consistent results: PMDD exists in a minority of women.
Historically, the pain and suffering of women have been dismissed, minimized, and negated. Similarly, women with PMDD have often had their experience invalidated. With the preponderance of evidence in its favor, PMDD has been placed in the main text of the DSM-5, opening the door for affected women to receive the attention full diagnostic status provides.
Numerous epidemiologic studies have demonstrated that premenstrual disorders (PMDs) begin during the teenage years. At least 20 % of adolescents experience moderate-to-severe premenstrual symptoms associated with functional impairment. Premenstrual syndrome (PMS) consists of physical and/or psychological premenstrual symptoms that interfere with functioning. Symptoms are triggered by ovulation and resolve within the first few days of menses. The prevalence of premenstrual dysphoric disorder (PMDD), a severe form of PMS accompanied by affective symptoms, is likely equal to or higher than in adults. The diagnosis of a PMD requires a medical and psychological history and physical examination but it is the daily prospective charting of bothersome symptoms for two menstrual cycles that will clearly determine if the symptoms are related to a PMD or to another underlying medical or psychiatric diagnosis. The number and type of symptoms are less important than the timing. Randomized controlled trials of pharmacologic treatments in teens with moderate-to-severe PMS and PMDD have yet to be performed. However, clinical experience suggests that treatments that are effective for adults can be used in adolescents. PMS can be ameliorated by education about the nature of the disorder, improving calcium intake, performing exercise and reducing stress, but to treat severe PMS or PMDD pharmacologic therapy is usually required. Eliminating ovulation with certain hormonal contraceptive formulations or gonadotropin-releasing hormone agonists will be discussed. Serotonergic agonists are a first-line therapy for adults, and some serotonin reuptake inhibitors such as fluoxetine and escitalopram can be administered safely to teens.
Unlabelled:
Catamenial migraine is a headache disorder occurring in reproductive-aged women relevant to menstrual cycles. Catamenial migraine is defined as attacks of migraine that occurs regularly in at least 2 of 3 consecutive menstrual cycles and occurs exclusively on day 1 to 2 of menstruation, but may range from 2 days before (defined as -2) to 3 days after (defined as +3 with the first day of menstruation as day +1). There are 2 subtypes: the pure menstrual migraine and menstrually related migraine. In pure menstrual migraine, there are no aura and no migraine occurring during any other time of the menstrual cycle. In contrast, menstrually related migraine also occurs in 2 of 3 consecutive menstrual cycles, mostly on days 1 and 2 of menstruation, but it may occur outside the menstrual cycle. Catamenial migraine significantly interferes with the quality of life and causes functional disability in most sufferers. The fluctuation of estrogen levels is believed to play a role in the pathogenesis of catamenial migraine. In this review, we discuss estrogen and its direct and indirect pathophysiologic roles in menstrual-related migraine headaches and the available treatment for women.
Target audience:
Obstetricians and gynecologists, family physicians.
Learning objectives:
After completing this CME activity, physicians should be better able to discuss the pathophysiology of catamenial migraine, identify the risk factors for catamenial migraine among women, and list the prophylactic and abortive treatments for migraines.
The effects of the steroid hormone 17β-estradiol and the neurotrophin BDNF on neuronal physiology have been well investigated. Numerous studies have demonstrated that each signal can exert powerful influences on the structure and function of synapses, and specifically on dendritic spines, both within short and long time frames. Moreover, it has been suggested that BDNF is required for the long-term, or genomic, actions of 17β-estradiol on dendritic spines, via its ability to regulate the expression of neurotrophins. Here we focus on the acute, or rapid effects, of 17β-estradiol and BDNF, and their ability to activate specific signalling cascades, resulting in alterations in dendritic spine morphology. We first review recent literature describing the mechanisms by which 17β-estradiol activates these pathways, and the resulting alterations in dendritic spine number. We then describe the molecular mechanisms underlying acute modulation of dendritic spine morphology by BDNF. Finally, we consider how this new evidence may suggest that the temporal interactions of 17β-estradiol and BDNF can occur more rapidly than previously reported. Building on these new data, we propose a novel model for the interactions of this steroid and neurotrophin, whereby rapid, non-genomic 17β-estradiol and acute BDNF signal in a co-operative manner, resulting in dendritic spine formation and subsequent stabilization in support of synapse and circuit plasticity. This extended hypothesis suggests an additional mechanism by which these two signals may modulate dendritic spines in a time-specific manner.
Selective serotonin re-uptake inhibitors have well-established efficacy for severe premenstrual syndrome and premenstrual dysphoric disorder. Efficacy has been reported with both continuous dosing (all cycle) and intermittent or luteal phase dosing (from ovulation to menses). Efficacy may be less with intermittent dosing, particularly for premenstrual physical symptoms. The efficacy of symptom-onset dosing (medication taken only on luteal days when symptoms occur) needs further systematic study. Women going through the menopausal transition may need to adjust their antidepressant dosing regimen due to the change in frequency of menstruation. Anxiolytics, calcium, chasteberry and cognitive-behaviour therapy may also have a role in the treatment of premenstrual symptoms.
Objective:
The purpose of this commentary is to provide an update on the research in both preclinical and clinical models regarding the cross-talk between estrogen and various serotonin molecular markers and the possible implications this may have on female-related mood disorders.
Conclusions:
Animal and human studies provide strong and consistent evidence suggesting that estrogen is able to regulate the serotonin pathway at various levels. The general trend that emerges is that estrogen administration increases serotonin availability by altering mRNA and protein levels of various serotonin markers and by decreasing serotonin breakdown. These effects may have direct implications on female mood disorders such as premenstrual disorders and depression during pregnancy, postpartum, and during the menopausal transition.
The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD).
In this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE (n=186) or placebo (n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP).
Mean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (-30.52±1.73 [SE] vs. -22.47±1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (-26.77±1.83 vs. -20.89±1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (≥50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥1 improvement) at last on-therapy cycle (p=.025).
Continuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD.
Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.
Premenstrual syndrome (PMS) refers to a constellation of regular, recurring, psychological or somatic complaints, or both, that occur specifically during the luteal phase of the ovulatory menstrual cycle and that resolve by the onset of or during menstruation. Many women of reproductive age experience PMS. Exercise has been proposed as a potential treatment in this regard, and several observational studies have reported a reduction in PMS and associated symptomatology in physically active women relative to their less active counterparts.
This review seeks to synthesize the available literature regarding the effects of exercise on PMS, with emphasis on findings from intervention studies. Studies were identified by systematically searching relevant databases.
Four eligible intervention studies were identified; all of these reported a reduction in PMS and related symptomatology after participation in exercise interventions. However, studies to date have recruited small samples and have been of low methodological quality.
There is a paucity of research on the effects of exercise on PMS. Although the American College of Obstetricians and Gynecologists (ACOG) has advised that regular aerobic exercise may help relieve PMS, to make any evidence-based policy recommendations regarding the effectiveness of exercise, more high-quality research is required.
Premenstrual symptoms are distressing for up to 20% of reproductive-aged women and are associated with impairment in interpersonal or workplace functioning for at least 3-8%. Typical symptoms of premenstrual syndrome and the severe form, premenstrual dysphoric disorder, include irritability, anger, mood swings, depression, tension/anxiety, abdominal bloating, breast pain and fatigue. The symptoms recur monthly and last for an average of 6 days per month for the majority of the reproductive years. For women with premenstrual dysphoric disorder, the symptoms can be as disabling as major depressive disorder. It has been estimated that affected women experience almost 3000 days of severe symptoms during the reproductive years. Until two decades ago, there were no effective treatments for severe premenstrual syndrome. Even in 2000, almost three-quarters of women in the USA with premenstrual disorders either did not seek help or sought treatment unsuccessfully from at least three clinicians for over 5 years. This review will focus on the epidemiology, diagnosis, treatment outcomes, quality of life and burden of illness for premenstrual disorders.
In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome.
The purpose of this study was to estimate the prevalence of perimenstrual symptoms in professionally employed women. Questionnaires were administered to all female nurses working at least 32 hr/wk in 7 different hospitals on the West Coast between October, 1987 and June, 1988. Of the 760 respondents, 594 were currently menstruating and met inclusion criteria. Symptoms frequently experienced by a majority of women included weight gain/swelling, anxiety/tension/irritability, fatigue, cramps, breast pain, mood swings, and food cravings. Symptoms were more prevalent in women under 30 years. Compared to white women, fewer Asians reported cramps and weight gain/swelling. More single women reported food cravings and depression/crying. Parity, cycle regularity, menses duration, and endometriosis were associated with perimenstrual cramps. Fewer women over 30 yrs experienced skin disorders and depression/crying. The only symptom experienced by more than 60% of women in all age groups was weight gain/swelling.
The use of mefenamic acid in the treatment of premenstrual syndrome (PMS) was investigated in 15 women over six menstrual cycles. A randomized, double-blind, cross-over, placebo-controlled design was used to overcome the methodologic criticisms of other medication trials in this condition. Mefenamic acid significantly improved many of the physical, mood, and performance symptoms associated with PMS. The physical symptoms that showed marked improvement were fatigue, headache, and general aches and pains (P less than .001). Most mood symptoms were improved, the most significant being freedom from mood swings (P less than .005).
One hundred forty-eight menstrual cycles were studied in 52 women, and in each cycle various parameters were measured to determine an objective means of assessing the syndrome. Daily mood assessment, body weight, plasma 17 beta-estradiol levels, and plasma progesterone levels were measured. The abdominal dimensions were measured in the lateral and anteroposterior diameters at the level of the umbilicus and 10 cm below; at the same time the same dimensions were measured as perceived by the patient. Mood score showed a marked increase during the premenstrual phase of each cycle. The symptom of bloatedness was marked during the premenstrual phase of the cycle. Despite these highly elevated scores for bloatedness there was no increase in body weight or the measured body dimensions in any plane. However, the patient's perception of body size did increase, and the discrepancy between the perceived body size and the actual body size (perception error) was significant.
The purpose of this study was to determine the prevalence of perimenstrual symptoms (PMS) in a free-living population of US women and to determine if prevalence estimates varied with parity, contraceptive status, characteristics of the menstrual cycle, and selected demographic variables. We identified all households from a census listing for five southeastern city neighborhoods that offered variation in racial composition and socioeconomic status. We ascertained all households in which there was one nonpregnant woman between the ages of 18 and 35 years per household. Of the 241 eligible women, 179 (74 per cent) participated in the study. Trained interviewers administered the Moos Menstrual Distress Questionnaire (MDQ) and other demographic measures to women between March and July 1979. Symptoms with a prevalence greater than 30 per cent included weight gain, headache, skin disorders, cramps, anxiety, backache, fatigue, painful breasts, irritability, mood swings, depression, or tension. Only 2 to 8 per cent of women found most of these severe or disabling. The exceptions were severe cramps reported by 17 per cent of women and severe premenstrual and menstrual irritability by 12 per cent. Cramps, backaches, fatigue, and tension were most prevalent during the menstruum; weight gain, skin disorders, painful breasts, swelling, irritability, mood swings, and depression were more prevalent in the premenstruum. Parity, oral contraceptive use, age, employment, education, and income were negatively associated with selected PMS. Use of an IUD, having long menstrual cycles, long menstrual flow, or heavy menstrual flow, and being able to predict the next period were positively associated with selected PMS. Race had both positive and negative effects on PMS.
The premenstrual syndrome (PMS) is a major clinical entity afflicting a large segment of the female population. Available information are descriptive in nature and the etiology of this syndrome remains unclear. In this review, both biochemical and psychosocial elements of the syndrome have been explored in an effort to redefine the pathophysiology of this seemingly multifactorial psychoneuroendocrine dysfunction. We propose that luteal phase sensitivity to and subsequent withdrawal from the central effects of the neuropeptides beta-endorphin and alpha-melanocyte-stimulating hormone result in a cascade of neuroendocrine changes within the brain-hypothalamus-pituitary complex. Modulation of neurotransmitter function by these peptides may produce alterations in mood and behavior as well as enhance pituitary release of prolactin and vasopressin. Variable gonadal steroid modulation of these responses from subject to subject likely accounts for the heterogeneous clinical manifestations of the PMS.
Daily symptom ratings were recorded in seven women with premenstrual tension syndrome for one month before and for up to two months after hysterectomy. Ovarian activity was monitored after operation by twice weekly measurements of total oestrogen and pregnanediol in 12-hour urine samples. Cyclical changes in mood persisted following hysterectomy with the greatest mental and physical symptoms occurring during the late luteal phase of the cycle. In contrast there was a marked decrease in activity and vigour ratings during the late luteal phase of the cycle and during menstruation. There was a small but significant improvement in symptoms in most women following hysterectomy. These results demonstrate that neither the presence of the uterus nor the occurrence of menstruation are necessary for the manifestation of the premenstrual tension syndrome and support the view that it has a hormonal basis.
To investigate whether danazol is more effective than placebo for the treatment of premenstrual syndrome (PMS), we conducted a randomized, double-blind, crossover study comparing three successive cycles of danazol (200 mg bid) to three cycles of placebo. Thirty-one women meeting rigorous criteria for a diagnosis of severe PMS over two pretreatment cycles were enrolled; 28 of these subjects completed at least one cycle of treatment with symptom recordings, which were entered into the analysis. A significant period effect confounded the planned within-subject analysis and therefore, the main treatment comparisons were confined to the first period only. Symptom scores on the Premenstrual Tension Self-Rating Scale (PMTS), Beck Depression Inventory (BDI), and a Visual Analogue Scale (VAS) were compared for the premenstrual week in the last cycle of treatment. For the 16 patients on danazol, scores on the PMTS decreased by an average of 14.0 (10.7) (standard deviation) points from a baseline of 25.4 (5.6) points. For the 12 patients on placebo, PMTS scores decreased by an average of 3.6 (9.5) points from a baseline of 23.5 (5.8) points (14.0 vs. 3.6; p = .0133, unpaired t-test). Seven (43.8%) of the subjects on danazol achieved a clinically relevant reduction of symptoms into the asymptomatic range (PMTS scores < or = 5) as compared to one (8.3%) of the subjects on placebo. Thus, danazol (200 mg bid) provided greater relief from severe PMS during the premenstrual week than did placebo.
To evaluate the efficacy of alprazolam in the treatment of premenstrual syndrome.
A randomized, double-blind, placebo-controlled, crossover trial of alprazolam during eight menstrual cycles.
Outpatient clinic at the National Institute of Mental Health, Bethesda, Md.
Twenty-two women with prospectively confirmed premenstrual syndrome entered this study. All subjects were either self-referred or were referred by their physicians. All reported having regular menstrual cycle lengths, were taking no medication, and were free of current or recent medical or psychiatric illness. Two subjects did not complete the trial.
Participants were assigned to receive alprazolam or placebo as follows: cycle 1, 0.25 mg of alprazolam or placebo three times daily beginning on menstrual cycle day 16; cycle 2, 0.50 mg of alprazolam or placebo three times daily according to the regimen during the first cycle; cycles 3 and 4, 0.75 mg of alprazolam or placebo three times daily from menstrual cycle day 16 and continued throughout the fourth menstrual cycle to evaluate the efficacy of relatively long-term (approximately 6 weeks) treatment with alprazolam.
Daily self-report symptoms ratings were completed during the entire study period.
We observed no significant differences in the severity of premenstrual symptom ratings during alprazolam administration compared with placebo on any scale except the Beck Depression Inventory Scale. The Beck Depression Inventory ratings demonstrated a statistically (F1,19 = 7.1, P < .05), but not clinically, significant improvement in depressive symptoms during alprazolam administration compared with placebo.
Our findings do not support alprazolam as a uniformly effective treatment for the symptoms of premenstrual syndrome.
To reevaluate whether spironolactone, a steroid receptor antagonist, is effective in improving premenstrual syndrome (PMS) in a double-blind, placebo-controlled cross over study.
Thirty-five women with PMS were given one tablet of 100 mg spironolactone or placebo daily from day 14 of the menstrual cycle until the first day of the following menstruation. Two pretreatment cycles were observed for diagnosis in each woman, followed by 6 treatment cycles with spironolactone and placebo applied in either the first or second 3 months. The assessment of symptoms and diagnosis of PMS were based on prospective daily self-ratings made by the women using a validated visual analogue scale.
The treatment with spironolactone was associated with an improvement in PMS symptoms compared to placebo as judged by significant decrease in negative mood symptom scores (p < 0.001) and somatic symptom scores (p < 0.001). Of the individual symptoms, spironolactone significantly improved irritability, depression, feeling of swelling, breast tenderness and food craving in comparison to placebo. A lasting effect of spironolactone was observed in women started with spironolactone after cross over to placebo.
Spironolactone appears to be an effective therapy for the negative mood changes and somatic symptoms in PMS.
To determine the efficacy of treating women with severe menstrual migraine headaches with GnRH agonist (GnRH-a) therapy, alone and combined with continuous estrogen-progestin "add-back."
Nonrandomized, prospective treatment study.
Outpatient clinic in a university medical center.
Five women who had repetitive, severe, migraine headaches limited to the perimenstrual period were selected carefully.
After 2 months of basal evaluation, all subjects received GnRH-a (leuprolide acetate depot formulation, 3.75 mg IM, monthly) for 10 months. Beginning with the 5th month, "add-back" therapy (the addition of transdermal E2, 0.1 mg daily, and oral medroxyprogesterone acetate, 2.5 mg daily) was initiated.
Patients rated headache severity from 0 (absent) to 3 (severe) each day; these were combined each month to obtain a cumulative score for that month. In addition, patients were asked their overall assessment of the treatments.
The mean headache scores for the GnRH-a treatment months (4.0 +/- 1.5, mean +/- SEM) and for the GnRH-a and "add-back" treatment months (3.1 +/- 0.7) were each significantly lower than those of the control months (15.3 +/- 2.4). The patients uniformly found both treatments to be well tolerated and near-curative for their condition.
Gonadotropin-releasing hormone agonist administration, alone or with "add-back" therapy, is a very effective treatment for carefully selected patients with severe, perimenstrual migraine headaches.
Our goal was to evaluate the efficacy and side effects of danazol 200 mg daily given only in the luteal phase of the menstrual cycle to treat premenstrual syndrome and premenstrual mastalgia.
We conducted a randomized, double-blind, placebo-controlled study of 3 menstrual cycles in a postgraduate medical school and National Health Service hospital. The subjects of the study were 100 women who had been referred to the premenstrual syndrome clinic at the North Staffordshire Hospital for the management of premenstrual syndrome and premenstrual breast pain. Outcome measures for the study included assessment of improvement in symptoms measured by specific daily visual analogue scales for 4 principal symptoms of premenstrual syndrome and for premenstrual mastalgia and assessment of side effects and adverse events.
Significant improvement in symptoms was seen in visual analog scores for mastalgia in months 1 (P =.03), 2 (P =.004), and 3 (P =.01) of the study during active therapy compared with placebo. No improvement was seen for any other symptom or for the global premenstrual syndrome score. Side effects on danazol and on placebo were equal and minimal.
Luteal phase-only danazol is not effective for the treatment of the general symptoms of premenstrual syndrome but appears highly effective for the relief of premenstrual mastalgia. This approach to therapy is associated with few side effects. Studies of cyclic mastalgia using strict diagnostic criteria are required to see whether the freedom from symptomatic side effects is found in longer-term studies and to determine whether such a regimen avoids potentially detrimental effects on the lipid status.
Antidepressant drugs, including specific serotonin reuptake inhibitors, have been shown to be beneficial in the treatment of premenstrual dysphoric disorders. The present study tests the efficacy of L-tryptophan, which acts specifically on serotonergic neurons, in this disorder.
In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day, and 34 were given placebo. The treatments were administered under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive menstrual cycles.
The Visual Analogue Scales (VAS) revealed a significant (p = .004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items of dysphoria, mood swings, tension, and irritability. The magnitude of the reduction from baseline in maximum luteal phase VAS-mood scores was 34.5% with L-tryptophan compared to 10.4% with placebo.
These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle has a beneficial effect in patients with premenstrual dysphoric disorder.
Does the evidence now available support the concept of premenstrual dysphoric disorder (PMDD) as a distinct clinical disorder such that the relative safety and efficacy of potential treatment can be evaluated? In a roundtable discussion of this question, a wealth of information was reviewed by a panel of experts. The key characteristics of PMDD, with clear onset and offset of symptoms closely linked to the menstrual cycle and the prominence of symptoms of anger, irritability, and internal tension, were contrasted with those of known mood and anxiety disorders. PMDD displays a distinct clinical picture that, in the absence of treatment, is remarkably stable from cycle to cycle and over time. Effective treatment of PMDD can be accomplished with serotinergic agents. At least 60% of patients respond to selective serotonin reuptake inhibitors (SSRIs). In comparison with other disorders, PMDD symptoms respond to low doses of SSRIs and to intermittent dosing. Normal functioning of the hypothalamic-pituitary-adrenal (HPA) axis, biologic characteristics generally related to the serotonin system, and a genetic component unrelated to major depression are further features of PMDD that separate it from other affective (mood) disorders. Based on this evidence, the consensus of the group was that PMDD is a distinct clinical entity. Potential treatments for this disorder can now be evaluated on this basis to meet the clear need for effective therapy.
Perimenstrual breast pain (cyclical mastalgia) is a common problem that can be sufficiently severe to interfere with usual activities, and has been associated with elevated mammography usage in young women. This study was undertaken to replicate clinic-based research on cyclical mastalgia, and to examine the association between this disorder and health-related behaviors and perceived stress. Using random digit dialing throughout Virginia, 874 women aged 18-44 were interviewed. Sixty-eight per cent of women experienced cyclical breast symptoms; 22% experienced moderate to extreme discomfort (classified as cyclical mastalgia). Hormonal contraceptive usage was associated with significantly less mastalgia and premenstrual syndrome (PMS). Smoking, caffeine consumption and perceived stress were associated with mastalgia (odds ratios = 1.52, 1.53 and 1.7, respectively). Young women (under 35 years) with mastalgia were more likely to have had a mammogram (20.2%) than those without mastalgia (9.9%). Most women with this disorder (77.5%) did not have PMS. The prevalence of cyclical mastalgia and its association with mammography replicate clinic-based findings. Associations with smoking and stress had not previously been reported. Prospective research is needed to determine the biopsychosocial factors contributing to this disorder.
We aimed to explore the prevalence and factor structure of premenstrual symptoms in a sample of Australian twins; to investigate phenotypic associations between reported premenstrual symptoms, personality and reproductive dimensions; and to identify the relative contributions of genes and environment to premenstrual symptoms and the extent of genetic and environmental covariation with the personality trait Neuroticism and lifetime major depression.
Seven hundred and twenty female twin pairs (454 monozygotic and 266 dizygotic) from the Australian National Health and Medical Research Council Twin Register reported on experience of 17 premenstrual symptoms during the previous 12 months. In the same questionnaire twins also responded to questions on symptom states, and personality dimensions including neuroticism. Interview data enabling diagnosis of lifetime history of DSM-IV major depression were also available. We fitted univariate and multivariate genetic models to the data.
Most frequently reported symptoms were breast tenderness/pain and bloating/weight gain, followed by affective symptoms. Twelve-month prevalence was 24% for the combination of symptoms and functional interference meeting a very rough approximation of DSM-III-R criteria for late luteal dysphoric disorder. Principal factor analysis identified a single premenstrual (PMS) factor. Additive genetic influences (44% of total variance) were identified for PMS. Although we found genetic correlations of 0.62 between reported PMS and neuroticism, and 0 70 with lifetime major depression, 39 % of the genetic variance of PMS was not explained by these factors.
Our findings support the existence of genetic influences on premenstrual symptoms, but we were unable to distinguish between liability to symptom experience and symptom reporting. Retrospective reporting may have contributed to our finding that PMS genes were shared in part with neuroticism and liability to lifetime major depression.
To determine the effectiveness of gonadotrophin-releasing hormone analogues (GnRHa) with and without hormonal add-back therapy in the management of premenstrual syndrome.
Randomised controlled trials were identified by searching multiple databases.
Exeter and North Devon Research and Development Support Unit and Keele University Academic Unit of Obstetrics and Gynaecology.
Women with pre-diagnosed premenstrual syndrome and/or premenstrual dysphoric disorder.
A meta-analysis of published randomised placebo-controlled trials assessing the use of GnRHa in the management of premenstrual syndrome. The standardised mean difference for each individual study and subsequently an overall standardised mean difference were calculated after demonstrating the consistency or homogeneity of the study results.
Overall improvement in premenstrual symptomatology and effectiveness of GnRHa with additional hormonal add-back therapy were the main outcome measures assessed in this analysis. A secondary analysis was performed to assess the effectiveness of GnRHa in treating physical and emotional symptoms.
Overall standardised mean difference for all trials that assessed the efficacy of GnRHa was -1.19 (95% confidence interval [CI] -1.88 to -0.51). The equivalent odds ratio was 8.66 (95% CI 2.52 to 30.26) in favour of GnRHa. GnRHa were more efficacious for physical than behavioural symptoms, although the difference was not statistically significant. The addition of hormonal add-back therapy to GnRHa did not appear to reduce the efficacy of GnRHa alone; standardised mean difference 0.12 (95% CI -0.35 to 0.58).
GnRHa appear to be an effective treatment in the management of premenstrual syndrome. The addition of hormonal add-back therapy to reduce side effects does not reduce efficacy.