Archives of Women's Mental Health

, Volume 21, Issue 6, pp 601–609 | Cite as

Both melatonin and meloxicam improved sleep and pain in females with primary dysmenorrhea—results from a double-blind cross-over intervention pilot study

  • Farahnaz Keshavarzi
  • Fariba Mahmoudzadeh
  • Serge Brand
  • Dena Sadeghi Bahmani
  • Fariba Akbari
  • Habibolah KhazaieEmail author
  • Mohammad Rasoul Ghadami
Original Article


Up to 25% of ovulating women suffer from primary dysmenorrhea, a condition associated with pain and transient-reduced quality of life, along with greater irritability and impaired sleep. In the present study, we asked whether and if so to what extent melatonin and meloxicam can improve subjective and objective sleep and reduce pain among women with primary dysmenorrhea (PD). To this end, we conducted a double-blind cross-over clinical trial lasting for three menstrual cycles. A total of 14 women (mean age M = 27.5 years) with primary dysmenorrhea took part in the study. At baseline, that is, during the first menstruation, they completed a visual analogue scale to rate pain; sleep continuity was assessed via actigraphs, and overall sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Next, participants were randomly assigned to one of two conditions, either melatonin during the second, and meloxicam during the third menstruation, or meloxicam during the second, and melatonin during the third menstruation. Neither participants nor investigators were aware of participants’ study assignment. During the second and third menstruations, the assessments described above were repeated. At baseline, sleep assessed both objectively and subjectively was impaired, and pain was high. Subjective sleep improved and pain decreased during the second and third menstruations irrespective of whether melatonin or meloxicam was administered first or second. Likewise, objective sleep efficiency increased and objective sleep latency shortened. The efficacy of melatonin was superior to that of meloxicam. The present pattern of results suggests that both melatonin and meloxicam are suitable to treat pain and PD-related sleep complaints among women with primary dysmenorrhea.


Primary dysmenorrhea Pain Sleep Melatonin Meloxicam 



We thank Nick Emler (University of Surrey, Surrey, UK) for proofreading the manuscript.

Authors’ contributions

FK, FM, SB, DSB, FA, HK, and MRG designed the study.

FK, FM, DSB, FA, HK, and MRG wrote the proposal for the ethical committee.

FK, FM, FA, HK, and MRG were highly involved in the recruitment of patients, the assessments, and interventions.

SB, DSB, and MRG performed the statistical analysis.

DSB, SB, and MRG wrote the draft of the manuscript.

DSB and SB integrated the co-authors’ comments.

DSB, SB, HK, and MRG completed the final version of the manuscript and submitted it.

Compliance with ethical standards

All procedures were approved by the institutional ethics committee of the KUMS, and performed in accordance with the rules laid down in the Declaration of Helsinki (Iranian Registry of Clinical Trials: IRCT2015031521475N1).

Conflict of interest

The authors declare that they have no conflicts of interests.

Financial disclosure

The entire study was performed without external funding.


  1. Abd-El-Maeboud KH, Kortam MA, Ali MS, Ibrahim MI, Mohamed RM (2014) A preliminary pilot randomized crossover study of uzara (Xysmalobium undulatum) versus ibuprofen in the treatment of primary dysmenorrhea. PLoS One 9(8):e104473. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL (2017) Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Med Rev 34:10–22. CrossRefGoogle Scholar
  3. Baker FC, Driver HS, Rogers GG, Paiker J, Mitchell D (1999) High nocturnal body temperatures and disturbed sleep in women with primary dysmenorrhea. Am J Phys 277(6 Pt 1):E1013–E1021Google Scholar
  4. Brand S, Gerber M, Puhse U, Holsboer-Trachsler E (2010) The relation between sleep and pain among a non-clinical sample of young adults. Eur Arch Psychiatry Clin Neurosci 260(7):543–551. CrossRefGoogle Scholar
  5. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213CrossRefGoogle Scholar
  6. Caruso S, Iraci M, Cianci S, Casella E, Fava V, Cianci A (2015) Quality of life and sexual function of women affected by endometriosis-associated pelvic pain when treated with dienogest. J Endocrinol Investig 38(11):1211–1218. CrossRefGoogle Scholar
  7. Caruso S, Iraci M, Cianci S, Fava V, Casella E, Cianci A (2016) Comparative, open-label prospective study on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain on 2 mg dienogest/30 microg ethinyl estradiol continuous or 21/7 regimen oral contraceptive. J Endocrinol Investig 39(8):923–931. CrossRefGoogle Scholar
  8. Chantler I, Mitchell D, Fuller A (2008) The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain. Clin J Pain 24(1):39–44. CrossRefGoogle Scholar
  9. Coghill RC, McHaffie JG, Yen YF (2003) Neural correlates of interindividual differences in the subjective experience of pain. Proc Natl Acad Sci U S A 100(14):8538–8542. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Coll AM, Ameen J (2006) Profiles of pain after day surgery: patients’ experiences of three different operation types. J Adv Nurs 53(2):178–187. CrossRefGoogle Scholar
  11. Collins SL, Moore RA, McQuay HJ (1997) The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain 72(1–2):95–97CrossRefGoogle Scholar
  12. Dawood MY (2006) Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol 108(2):428–441. CrossRefGoogle Scholar
  13. de Mello NR, Baracat EC, Tomaz G, Bedone AJ, Camargos A, Barbosa IC, de Souza RN, Rumi DO, Martinez Alcala FO, Velasco JAA, Cortes RJR (2004) Double-blind study to evaluate efficacy and safety of meloxicam 7.5 mg and 15 mg versus mefenamic acid 1500 mg in the treatment of primary dysmenorrhea. Acta Obstet Gynecol Scand 83(7):667–673. CrossRefGoogle Scholar
  14. Farrahi MJ, Nakhaee N, Sheibani V, Garrusi B, Amirkafi A (2012) Reliability and validity of the Persian version of the Pittsburgh Sleep Quality Index (PSQI-P). Sleep Breath 16:79–82CrossRefGoogle Scholar
  15. Gorny SW, Allen RP, Krausmann DT, Cammarata J, Earley CJ (1997) A parametric and sleep hysteresis approach to assessing sleep and wake from wrist activity meter with enhanced frequency range. Paper presented at the 11th annual meeting of the associated professional sleep societies, June 10–15. San Francisco, CAGoogle Scholar
  16. Iacovides S, Avidon I, Baker FC (2015) What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update 21(6):762–778. CrossRefGoogle Scholar
  17. Iacovides S, Avidon I, Bentley A, Baker FC (2009) Diclofenac potassium restores objective and subjective measures of sleep quality in women with primary dysmenorrhea. Sleep 32(8):1019–1026CrossRefGoogle Scholar
  18. Julious SA (2005) Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat 4(4):287–291. CrossRefGoogle Scholar
  19. Latthe PM, Champaneria R (2014) Dysmenorrhoea. BMJ Clin EvidGoogle Scholar
  20. Lautenbacher S (2017) Sleep and pain are definitely coupled-but how tight is this coupling? Pain 159:3–4. CrossRefGoogle Scholar
  21. Lautenbacher S, Kundermann B, Krieg JC (2006) Sleep deprivation and pain perception. Sleep Med Rev 10(5):357–369. CrossRefGoogle Scholar
  22. Marshansky S, Mayer P, Rizzo D, Baltzan M, Denis R, Lavigne GJ (2017) Sleep, chronic pain, and opioid risk for apnea. Prog Neuro-Psychopharmacol Biol Psychiatry. CrossRefGoogle Scholar
  23. Onen SH, Alloui A, Gross A, Eschallier A, Dubray C (2001) The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects. J Sleep Res 10(1):35–42CrossRefGoogle Scholar
  24. Posa L, De Gregorio D, Gobbi G, Comai S (2017) Targeting melatonin MT2 receptors: a novel pharmacological avenue for inflammatory and neuropathic pain. Curr Med Chem 24:1. CrossRefGoogle Scholar
  25. Price DD (2000) Psychological and neural mechanisms of the affective dimension of pain. Science 288(5472):1769–1772CrossRefGoogle Scholar
  26. Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M, Perlis M, Nissen C (2010) The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev 14(1):19–31. CrossRefGoogle Scholar
  27. Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T (2006) Sleep loss and REM sleep loss are hyperalgesic. Sleep 29(2):145–151CrossRefGoogle Scholar
  28. Roehrs T, Roth T (2005) Sleep and pain: interaction of two vital functions. Semin Neurol 25(1):106–116. CrossRefGoogle Scholar
  29. Roehrs TA, Roth T (2017) Increasing presurgery sleep reduces postsurgery pain and analgesic use following joint replacement: a feasibility study. Sleep Med 33:109–113. CrossRefGoogle Scholar
  30. Vitale SG, Rossetti P, Corrado F, Rapisarda AM, La Vignera S, Condorelli RA, Valenti G, Sapia F, Lagana AS, Buscema M (2016) How to achieve high-quality oocytes? The key role of Myo-inositol and melatonin. Int J Endocrinol 2016:4987436. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Zhu C, Xu Y, Duan Y, Li W, Zhang L, Huang Y, Zhao W, Wang Y, Li J, Feng T, Li X, Hu X, Yin W (2017) Exogenous melatonin in the treatment of pain: a systematic review and meta-analysis. Oncotarget 8(59):100582–100592. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyKermanshah University of Medical SciencesKermanshahIran
  2. 2.Sleep Disorders Research Center, Farabi HospitalKermanshah University of Medical SciencesKermanshahIran
  3. 3.Psychiatric Clinics, Center for Affective, Stress and Sleep DisordersUniversity of BaselBaselSwitzerland
  4. 4.Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial HealthUniversity of BaselBaselSwitzerland

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