The effect of premenstrual symptoms on activities of daily life

doi:10.1016/j.fertnstert.2009.04.023

Fertility and Sterility

Volume 94, Issue 3, August 2010, Pages 1059-1064

https://doi.org/10.1016/j.fertnstert.2009.04.023 Get rights and content

Objective

To assess impact of premenstrual symptoms on activities of women's daily lives (ADL).

Design

Cross-sectional population-based survey.

Setting

Market research company.

Patient(s)

A total of 4,085 women aged 14–50 years recruited by random telephone digit dialing in France, Germany, Hungary, Italy, Spain, the United Kingdom, Brazil, and Mexico.

Intervention(s)

None.

Main Outcome Measure(s)

A telephone interview checklist of 23 premenstrual symptoms, sociodemographic and lifestyle variables, and ADL effects (global question and seven areas). Stepwise regression measured the effect of premenstrual symptoms and sociodemographic factors on ADL.

Result(s)

Symptoms and symptom domains (physical and mental) had similar negative effects on ADL. Activities of daily life were predominantly affected by symptom severity. Income level, age, and country also significantly affected ADL. In all, 2,638 women (64.6%) were minimally affected in ADL, 981 (24%) were moderately affected, and 454 (11.1%) were severely affected.

Conclusion(s)

Both physical and mental premenstrual symptoms have significant impact on quality of life, assessed as ADL. Up to 35% of women of reproductive age in Europe and Latin America were moderately or severely affected in ADL by cyclical premenstrual symptoms.

Section snippets

Effect of symptoms on activities of daily life

Premenstrual syndrome is characterized by many different symptoms. Do these symptoms equally affect activities of daily life (ADL), or is there a subset of symptoms with a particularly important impact? Using the same data set, we have already shown that premenstrual symptoms can be divided into two main domains and five dimensions on cluster analysis (Dennerstein et al., unpublished data). Do these domains/dimensions have the same impact on ADL? Is the relationship between symptoms and ADL

Factors associated with impact of symptoms on ADL

This section seeks to establish which sociodemographic and lifestyle variables influence the effect of premenstrual symptoms on ADL.

Clinical relevance of effect of perceived symptom severity on ADL

Not all women will experience a significant effect of premenstrual symptoms on ADL. We seek to establish whether we can statistically define mild, moderate, and severe effects.

Design

During June and July 2003, computer-assisted telephone interviews consisting of a series of questions about premenstrual symptoms were conducted with 4,085 women of reproductive age in European countries (Germany, n = 531; Italy, n = 505, France, n = 501; United Kingdom [UK], n = 500; Spain, n = 500; Hungary, n = 500) and Latin American countries (Brazil, n = 548; and Mexico, n = 500).

Institutional review board approval was not sought because this was a questionnaire survey with no

Results

A total of 4,085 women from Latin American (n = 1048) and European (n = 3037) countries participated in the study. The mean age of participating women was 31.44 years, with the majority of women being in the age groups 30–39 years (29.8%) or 20–29 years (27.5%). Brazilian and Mexican samples were characterized by a slightly younger age. French and German women had a higher education level than women in other countries. Important disparities existed in work participation, in particular the

Discussion

All premenstrual symptoms were found to have significant effects on ADL. There were no differences between the impact of physical and mental premenstrual symptoms in this regard. We have previously shown in the same data set that physical premenstrual symptoms are the most prevalent, as measured by severity, duration (number of affected menstrual cycles), or both (Dennerstein et al., unpublished data). In terms of women's assessment of overall impact of severity of premenstrual symptoms, we

Acknowledgment

The authors thank TNS Emnid (Bielefeld, Germany) for its assistance in the development of the questionnaire; and the following fieldwork agencies: OPERA (UK); PLM (France); Demoscopia (Spain); Nomesis (Italy); MASMI (Hungary); AC Nielsen (Brazil); and Analitica (Mexico).

References (13)

E.W. Freeman
Premenstrual syndrome and premenstrual dysphoric disorder: definitions and diagnosis
Psychoneuroendocrinology
(2003)
L.S. Cohen et al.
Prevalence and predictors of premenstrual dysphoric disorder (PMDD) in older premenopausal women. The Harvard Study of Moods and Cycles
J Affect Disord
(2002)
American Psychiatric Association
Diagnostic and statistical manual of mental disorders
(1994)
ACOG Practice Bulletin, clinical management guidelines for obstetrician-gynecologists number 15, April 2000. Premenstrual syndrome
Int J Gynecol Obstet
(2001)
B.B. Dean et al.
Evaluating the criteria used for identification of PMS
J Womens Health
(2006)
H.U. Wittchen et al.
Prevalence, incidence and stability of premenstrual dysphoric disorder in the community
Psychol Med
(2002)

There are more references available in the full text version of this article.

Cited by (39)

Can animal models resemble a premenstrual dysphoric condition?
2022, Frontiers in Neuroendocrinology
Citation Excerpt :
On the other hand, ALLO also induces anxiolytic actions at high doses, reinforcing the notion that alterations in the GABAAR sensitivity might be present. Because PMD symptoms begin in the luteal phase and are resolved shortly after menstruation, it is proposed that gonadal steroids (estrogen and progesterone) are involved in its pathophysiology (Dennerstein et al., 2010). The late luteal phase happens together with a rapid fall in plasma progesterone levels (McLachlan et al., 1987), and mood symptoms correlated with this rapid progesterone withdrawal (Hammarback et al., 1985; Wang et al., 1996).
Around 80% of women worldwide suffer mild Premenstrual Disorders (PMD) during their reproductive life. Up to a quarter are affected by moderate to severe symptoms, and between 3% and 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.
Treatment of premenstrual dysphoric disorder with the GABA<inf>A</inf> receptor modulating steroid antagonist Sepranolone (UC1010)—A randomized controlled trial
2017, Psychoneuroendocrinology
Citation Excerpt :
The disorder is typified by a recurrent cluster of mental symptoms such as irritability, depressed mood, aggression and emotional lability that consistently recur only in the premenstrual (luteal) phase of the menstrual cycle (APA, 2013; O’Brien et al., 2011). Quality of life for these women is reduced due to a significant negative impact on social life, relations and work performance during the premenstrual period (Dennerstein et al., 2010). The pathophysiology of PMDD is not yet fully understood, but a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone (3α-OH-5α-pregnan-20-one), has been established (Backstrom et al., 2003).
Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABA_A receptor. 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.
The objective was to test whether inhibition of allopregnanolone by treatment with the GABA_A modulating 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.
This was an explorative randomized, double-blind, placebo-controlled study.
Swedish multicentre study with 10 centers.
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.
Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.
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).
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.
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.
Allopregnanolone and mood disorders
2014, Progress in Neurobiology
Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3–8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3–8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone.
These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.
Understanding and attitudes of Brazilian men with regard to premenstrual syndrome
2013, International Journal of Gynecology and Obstetrics
Citation Excerpt :
It has been reported that approximately 40% of women experience PMS symptoms that lead them to seek medical consultation, and approximately 5% of this latter group has premenstrual dysphoric disorder, which may provoke a reduction or loss of quality of life [1–3]. A multinational study showed that PMS can affect women's routine activities moderately (24.0%) or severely (11.1%) [4]. Many women perceive monthly bleeding as a body time marker and many expect to have PMS symptoms [5].
To assess the understanding and attitudes of Brazilian men regarding premenstrual syndrome (PMS).
In a survey-based study between September 2007 and April 2008, information was collected from men aged 18–40 years who were attending public healthcare services or were university and faculty staff at 5 cities in different geographic regions of Brazil and the Federal District.
In total, 527 men were interviewed. Of these, 86.3% had heard of PMS, and 34.3% reported that it is a natural part of the menstrual cycle. The most commonly reported characteristics of PMS were emotional symptoms (55.2%), including nervousness or anxiety; irritability, anger, or aggressiveness; and a greater tendency to start arguments and fights. A significant relationship was found between men who had heard of PMS and being aged 20–35 years, having a university degree, being white, and belonging to a higher socioeconomic stratum (P < 0.001). Furthermore, men with a university degree were more likely to know that PMS symptoms occur before menses (P < 0.004).
Many of the men interviewed were knowledgeable about PMS symptoms; however, this awareness was more common among men of higher socioeconomic strata with more years of schooling.
Homeopathic treatment of premenstrual syndrome: A case series
2013, Homeopathy
Observational, prospective study to describe the homeopathic management of premenstrual syndrome (PMS) by a group of French physicians.
Women with PMS for >3 months were prescribed individualized homeopathic treatment. The intensity of 10 clinical symptoms of PMS was scored individually at inclusion and at a 3–6 month follow-up visit: absent = 0, mild = 1, moderate = 2, severe = 3. Total symptom score (range: 0–30) was calculated and compared for each patient at inclusion and at follow-up. PMS impact on daily activities (quality of life, QoL) was compared at inclusion and follow-up as: none, mild, moderate, severe, very severe.
Twenty-three women were prescribed homeopathic treatment only (mean age: 39.7 years). Folliculinum (87%) was the most frequently prescribed homeopathic medicine followed by Lachesis mutus (52.2%). The most common PMS symptoms (moderate or severe) at inclusion were: irritability, aggression and tension (87%), mastodynia (78.2%) and weight gain and abdominal bloating (73.9%); and the most common symptoms at follow-up were: irritability, aggression and tension (39.1%), weight gain and abdominal bloating (26.1%) and mastodynia (17.4%). Mean global score for symptom intensity was 13.7 at inclusion and 6.3 at follow-up. The mean decrease in score (7.4) was statistically significant (p < 0.0001). Twenty-one women reported that their QoL also improved significantly (91.3%; p < 0.0001).
Homeopathic treatment was well tolerated and seemed to have a positive impact on PMS symptoms. Folliculinum was the most frequent homeopathic medicine prescribed. There appears to be scope for a properly designed, randomized, placebo-controlled trial to investigate the efficacy of individual homeopathic medicines in PMS.
A rodent model of premenstrual dysphoria: Progesterone withdrawal induces depression-like behavior that is differentially sensitive to classes of antidepressants
2012, Behavioural Brain Research
Citation Excerpt :
General locomotor activity was assessed as tracklength using Viewer automated tracking software (Biobserve: Bonn, Germany). Pain, including fibromyalgia and other non-specific somatic complaints are common not only to PMDD but also to major depression [1,75,76]. Sex steroid hormones are also thought to be involved in pain threshold [77,78] and sex differences also been established [78,79].
Premenstrual dysphoric disorder (PMDD) is characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. We demonstrate robust and reproducible depression-like behavior during progesterone withdrawal (PWD) protocols with different methodological variables. Comparable immobility in the forced swim test was evident with different routes of administration (i.e. injections vs. implants), with and without exogenous estrogens in addition to progesterone, and in both single and multiple withdrawal paradigms. Furthermore, withdrawal from physiological doses of progesterone resulted in modest social withdrawal in the social preference test and anhedonia in the saccharin preference test without altering general activity levels or total liquid consumption. However, progesterone withdrawal did not alter serotonin levels in the cortex or hippocampus. Furthermore tryptophan depletion did not augment immobility during PWD. Neither fluoxetine nor duloxetine reduced depression-like behavior during PWD in the forced swim test. In contrast, the tricyclic antidepressant, amitriptyline, was effective in reducing the immobility in forced swim test. These data demonstrate that progesterone withdrawal is a reproducible model of PMDD in several critical behavioral domains. Furthermore, these data do not support alterations in serotonin levels in the etiology of hormonally induced depression.

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: L.D. serves on the expert advisory board for Boehringer Ingelheim and receives speaker honoraria from Boehringer Ingelheim, Wyeth Pharmaceuticals, and Bayer Schering; P.L. serves as a regular senior consulting statistician for Merck Kgaa, Sanofi-Aventis, Ipsen, Serono, and Bayer Schering; T.C.B. receives speaker honoraria from Bayer Schering Pharma and is a grant application referee for Schering Plough; K.H. is an employee of Bayer Schering Pharma.

: This study was supported by Bayer Schering Pharma, Women's Health Care, Berlin, Germany. Data were analyzed independently of the company by the first two authors.

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Pyschological factorsThe effect of premenstrual symptoms on activities of daily life

Objective

Design

Setting

Patient(s)

Intervention(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Effect of symptoms on activities of daily life

Factors associated with impact of symptoms on ADL

Clinical relevance of effect of perceived symptom severity on ADL

Design

Results

Discussion

Acknowledgment

Psychoneuroendocrinology

J Affect Disord

Diagnostic and statistical manual of mental disorders

ACOG Practice Bulletin, clinical management guidelines for obstetrician-gynecologists number 15, April 2000. Premenstrual syndrome

Int J Gynecol Obstet

Evaluating the criteria used for identification of PMS

J Womens Health

Prevalence, incidence and stability of premenstrual dysphoric disorder in the community

Psychol Med

Pyschological factors
The effect of premenstrual symptoms on activities of daily life