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Premenstrual dysphoric disorder: How to alleviate her suffering

Current Psychiatry. 2012 April;11(04):22-41
April 1, 2012|Current Psychiatry
Laura Wakil, MD
Author and Disclosure Information

Laura Wakil, MD
Third-Year Psychiatry Resident, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC
Samantha Meltzer-Brody, MD, MPH
Director, Perinatal Psychiatry Program, University of North Carolina Center for Women’s Mood Disorders, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC
Susan Girdler, PhD
Director, UNC Stress and Health Research Program, Menstrually Related Mood Disorders Program, University of North Carolina Center for Women’s Mood Disorders, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC

Accurate diagnosis, tailored treatments can greatly improve women’s quality of life

For a discussion of the etiology of PMDD, see Box 1.

Table

DSM-IV-TR research criteria for PMDD

  1. In most menstrual cycles of the past year, ≥5 of the following symptoms must be present for most of the time during the last week of the luteal phase, begin to remit within a few days after the onset of the follicular phase, and are absent in the week postmenses, with ≥1 of the symptoms being either 1, 2, 3, or 4:
  2. The disturbance markedly interferes with work or school or with usual social activities and relationships with others (eg, avoidance of social activities, decreased productivity and efficiency at work or school)
  3. The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, dysthymic disorder, or a personality disorder (although it may be superimposed on any of these disorders)
  4. Criteria A, B, and C must be confirmed by prospective daily ratings during ≥2 consecutive symptomatic cycles (The diagnosis may be made provisionally prior to this confirmation)
Source: Reference 6

Box 1

Reproductive hormones in PMDD etiology

Although questions remain about the pathogenesis of premenstrual dysphoric disorder (PMDD), literature documents the role of gonadal steroids (estrogen and progesterone) in the etiology of premenstrual syndrome (PMS)/PMDD and suggests that women with PMDD are differentially sensitive to the normal physiologic fluctuations of gonadal hormones throughout the menstrual cycle.a

The first half of the menstrual cycle—the follicular phase—begins with increasing levels of follicular stimulating hormone (FSH) leading to maturity of the ovarian follicle. Once the follicle is ripe, the luteal phase of the menstrual cycle begins with a surge in luteinizing hormone (LH), which results in ovulation of the mature follicle, followed by increased secretion of progesterone, followed by increased estrogen secretion. The system is regulated via negative feedback, and high levels of progesterone decrease gonadotropin-releasing hormone (GnRH) pulse frequency, which leads to decreased secretion of FSH and LH, and subsequent decline of estrogen and progesterone. If the ovarian follicle is not fertilized, menstruation begins and FSH levels rise again, initiating the follicular phase of the menstrual cycle.

Fluctuations in reproductive steroid levels have been implicated in the etiology of PMDD from studies showing that oophorectomy and ovulation inhibitors (GnRH agonists) relieve symptoms.b Some researchers proposed that symptoms are related to the drop of progesterone in the late luteal phase; however, many women have symptoms that start at ovulation or during the early luteal phase before the fall in progesterone concentrations.c PMS symptoms may occur independently of the mid-to-late luteal phase.d Because production of gonadal steroids does not differ between women with or without PMS or PMDD,e it may be that follicular or periovulatory changes in levels of estradiol or progesterone secretion trigger symptoms of PMDD in susceptible women, while women without PMDD appear to be immune to these effects of gonadal steroids. This idea is supported by a study showing that pharmacologic induction of a hypogonadal state eliminates symptoms in most women with severe PMS, while “adding back” estrogen or progesterone within the context of hypogonadism elicits return of PMS symptoms in those with PMS but not in controls.a

Abnormalities in serotonin levels also may contribute to PMDD.f In 1 study, a serotonin receptor antagonist precipitated return of symptoms within 24 hours of administration in women with PMDD but not in controls.g PMDD symptoms also can be evoked by depleting the serotonin precursor tryptophan.h When women with PMDD received paroxetine at different phases of their menstrual cycle, they showed fluctuations in serotonergic function across their cycles; these fluctuations were not seen in controls.i Other neurotransmitters implicated in PMDD include γ-aminobutyric acid (GABA),j glutamate,k lower levels of cortisol and beta-endorphins,l and an abnormal stress response.m

Other studies have focused on differing concentrations of luteal phase hormonesn and gene associations. Two studies suggested that PMDD is heritableo,p and other studies have looked at the association between specific psychological traits that are more prominent in PMDD and single nucleotide polymorphisms in the estrogen receptor alpha gene.q,r

Thyroid hormones also may play a role in the etiology of PMS/PMDD. Thyroid function tests have shown greater variability in women with PMS vs controls,s although this variability appears to be limited to women with a sexual abuse history.t Other studies have evaluated hormones regulated across the circadian and sleep-wake cycles, including melatonin, cortisol, thyroid-stimulating hormone, and prolactin, which suggests that although levels of these hormones may not differ between women with PMDD and controls, the timing of their excretion may vary.s Additionally, women with PMDD are characterized by prefrontal brain asymmetry on electroencephalography that also is evident in patients with major depressive disorder.u

There also may be dysregulation of allopregnanolone (ALLO) in women with PMDD.v,w ALLO is a metabolite of progesterone that is a neurosteroid produced in the brain as well as in the ovary and adrenals.v It produces anxiolytic effects by acting as a modulator of GABA receptors.x In PMDD, ALLO levels may influence the severity of premenstrual symptoms.w

References

  1. Schmidt PJ, Nieman LK, Danaceau MA, et al. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med. 1998;338(4):209-216.
  2. Muse KN, Cetel NS, Futterman LA, et al. The premenstrual syndrome. Effects of “medical ovariectomy.” N Engl J Med. 1984;311(21):1345-1349.
  3. Yonkers KA, O’Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008;371(9619):1200-1210.
  4. Schmidt PJ, Nieman LK, Grover GN, et al. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. N Engl J Med. 1991;324(17):1174-1179.
  5. Rubinow DR, Schmidt PJ. The neuroendocrinology of menstrual cycle mood disorders. Ann N Y Acad Sci. 1995;771:648-659.
  6. Steiner M, Pearlstein T. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J Clin Psychiatry. 2000;61(suppl 12):17-21.
  7. Roca CA, Schmidt PJ, Smith MJ, et al. Effects of metergoline on symptoms in women with premenstrual dysphoric disorder. Am J Psychiatry. 2002;159(11):1876-1881.
  8. Menkes DB, Coates DC, Fawcett JP. Acute tryptophan depletion aggravates premenstrual syndrome. J Affect Disord. 1994;32(1):37-44.
  9. Inoue Y, Terao T, Iwata N, et al. Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests. Psychopharmacology (Berl). 2007;190(2):213-219.
  10. Epperson CN, Haga K, Mason GF, et al. Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry. 2002;59(9):851-858.
  11. Batra NA, Seres-Mailo J, Hanstock C, et al. Proton magnetic resonance spectroscopy measurement of brain glutamate levels in premenstrual dysphoric disorder. Biol Psychiatry. 2008;63(12):1178-1184.
  12. Straneva PA, Maixner W, Light KC, et al. Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder. Health Psychol. 2002;21(4):358-367.
  13. Epperson CN, Pittman B, Czarkowski KA, et al. Luteal-phase accentuation of acoustic startle response in women with premenstrual dysphoric disorder. Neuropsychopharmacology. 2007;32(10):2190-2198.
  14. Thys-Jacobs S, McMahon D, Bilezikian JP. Differences in free estradiol and sex hormone-binding globulin in women with and without premenstrual dysphoric disorder. J Clin Endocrinol Metab. 2008;93(1):96-102.
  15. Payne JL, Klein SR, Zamoiski RB, et al. Premenstrual mood symptoms: study of familiality and personality correlates in mood disorder pedigrees. Arch Womens Ment Health. 2009;12(1):27-34.
  16. Kendler KS, Karkowski LM, Corey LA, et al. Longitudinal population-based twin study of retrospectively reported premenstrual symptoms and lifetime major depression. Am J Psychiatry. 1998;155(9):1234-1240.
  17. Miller A, Vo H, Huo L, et al. Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls. J Psychiatr Res. 2010;44(12):788-794.
  18. Huo L, Straub RE, Roca C, et al. Risk for premenstrual dysphoric disorder is associated with genetic variation in ESR1, the estrogen receptor alpha gene. Biol Psychiatry. 2007;62(8):925-933.
  19. Girdler SS, Pedersen CA, Light KC. Thyroid axis function during the menstrual cycle in women with premenstrual syndrome. Psychoneuroendocrinology. 1995;20(4):395-403.
  20. Girdler SS, Thompson KS, Light KC, et al. Historical sexual abuse and current thyroid axis profiles in women with premenstrual dysphoric disorder. Psychosom Med. 2004;66(3):403-410.
  21. Accortt EE, Stewart JL, Coan JA, et al. Prefrontal brain asymmetry and pre-menstrual dysphoric disorder symptomatology. J Affect Disord. 2011;128(1-2):178-183.
  22. Paul SM, Purdy RH. Neuroactive steroids. FASEB J. 1992;6(6):2311-2322.
  23. Girdler SS, Straneva PA, Light KC, et al. Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol Psychiatry. 2001;49(9):788-797.
  24. Brot MD, Akwa Y, Purdy RH, et al. The anxiolytic-like effects of the neurosteroid allopregnanolone: interactions with GABA(A) receptors. Eur J Pharmacol. 1997;325(1):1-7.

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