Gender aspects of the pain syndrome

  • K O Ostrovska Zdorovoe pokolenie, Private Clinic, Dnipro, Ukraine
Keywords: pain, pain syndrome, gender aspects, sex differences, sex hormones, estrogen, progesterone, testosterone


In recent years, the subject of sex differences in the pain experience attracts a growing interest. The epidemiological and clinical data indicate that women have increased risk of chronic pain, and according to some sources, even experience more intense pain.
The hypothetical biological mechanisms underlying sex differences in pain perception consist in the modulating effects produced by sex hormones in relation to the neural substrate. This is confirmed by data on the distribution of gonadal hormones and their receptors in the areas of the peripheral and central nervous system that provide nociceptive transmission.
The complexity of the estradiol and progesterone effects on pain sensitivity lies in the fact that, according to various data, both have pre-nociceptive and antinociceptive effects, and testosterone appears to be more characterized by antinociceptive properties. The lion’s share of researches demonstrates the effect of a clinical pain exacerbation during the menstrual cycle.
There is irrefutable information about gender differences in responses to drug and non-drug pain treatment, although the results vary depending on a specific therapy and may depend on pain characteristics. Since the recommended dosage of a medication is often based on an “average” male weigh 70 kg, female patients may be facing the risk of increased therapeutic or adverse effects of a drug. The cause is in a higher average percentage of body fat, a lower mean body weight, which contributes to higher median drug concentrations compared with male patients.
At present, the available evidence does not allow adapting the methods of pain syndrome treatment to a gender. However, such innovations are quite possible and desirable in the foreseeable future. Additional studies will be required to clarify the mechanisms that determine sex differences in pain responses in order to provide adequate pain relief, according to the patient’s needs.


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Author Biography

K O Ostrovska, Zdorovoe pokolenie, Private Clinic, Dnipro, Ukraine

The Ukrainian Society for Gender and Anti-Aging Medicine


Robinson ME, Riley JL III, Myers CD, et al. Gender role expectations of pain: relationship to sex differences in pain. J Pain2001; 2: 251–7.

Wise EA, Price DD, Myers CD, Heft MW, Robinson ME. Gender role expectations of pain: relationship to experimental pain perception. Pain 2002; 96: 335.

Defrin R, Shramm L, Eli I. Gender role expectations of pain is associated with pain tolerance limit but not with pain threshold. Pain 2009; 145: 230–6.

Walsh CA, Jamieson E, MacMillan H, Boyle M. Child abuse and chronic pain in a community survey of women. J Interpers Violence 2007; 22: 1536–54.

Fillingim RB, Edwards RR. Is self-reported childhood abuse history associated with pain perception among healthy young women and men? Clin J Pain 2005; 21: 387–97.

Edwards PW, Zeichner A, Kuczmierczyk AR, Boczkowski J. Familial pain models: the relationship between family history of pain and current pain experience. Pain 1985; 21: 379.

Fillingim RB, Edwards RR, Powell T. Sex-dependent effects of reported familial pain history on recent pain complaints and experimental pain responses. Pain 2000; 86: 87–94

Gerdle B, Bjork J, Coster L, Henriksson K, Henriksson C, Bengtsson A. Prevalence of widespread pain and associations with work status: a population study. BMC Musculoskeletal Disorders 2008; 9: 102.

Edwards RR, Augustson E, Fillingim RB. Differential relationships between anxiety and treatment-associated pain reduction among male and female chronic pain patients. Clin J Pain 2003; 19: 208–16.

Fillingim RB, Doleys DM, Edwards RR, Lowery D. Clinical characteristics of chronic back pain as a function of gender and oral opioid use. Spine 2003; 28: 143–50.

Keefe FJ, Lefebvre JC, Egert JR, Affleck G, Sullivan MJ, Caldwell DS. The relationship of gender to pain, pain behavior, and disability in osteoarthritis patients: the role of catastrophizing. Pain 2000; 87: 325–34.

Barnabe C, Bessette L, Flanagan C, et al. Sex differences in pain scores and localization in inflammatory arthritis: A systematic review and metaanalysis. J Rheumatol 2012; 39: 1221–30.

Tang YR, Yang WW, Wang YL, Lin L. Sex differences in the symptoms and psychological factors that influence quality of life in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol 2012; 24: 702–7.

Robinson ME, Wise EA, Riley JLI. Sex differences in clinical pain: a multi-sample study. J Clin Psychol Med Settings 1998; 5: 413–23.

Turk DC, Okifuji A. Does sex make a difference in the prescription of treatments and the adaptation to chronic pain by cancer and non-cancer patients? Pain 1999; 82: 139–48.

Ruau D, Liu LY, Clark JD, Angst MS, Butte AJ. Sex differences in reported pain across 11000 patients captured in electronic medical records. J Pain 2012; 13: 228–34.

Craft RM. Modulation of pain by estrogens. Pain 2007; 132: S3– S12.

Craft RM, Mogil JS, Aloisi AM. Sex differences in pain and analgesia: the role of gonadal hormones. Eur J Pain 2004; 8: 397

Greenspan JD, Craft RM, LeResche L, et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain 2007;132:S26-S45.

Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009;10:447–85.

Aloisi AM, Bonifazi M. Sex hormones, central nervous system and pain. Horm Behav 2006;50:1–7.

Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: data from the American migraine study II. Headache 2001;41:646–57.

Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci 2006; 26: 5777–85.

Cairns BE, Gazerani P. Sex-related differences in pain. Maturitas 2009; 63: 292–6.

LeResche L, Mancl L, Sherman JJ, Gandara B, Dworkin SF. Changes in temporomandibular pain and other symptoms across the menstrual cycle. Pain 2003; 106: 253.

Ader DN, South-Paul J, Adera T, Deuster PA. Cyclical mastalgia: prevalence and associated health and behavioral factors. J Psychosom Obstet Gynaecol 2001; 22: 71–6.

Silberstein SD, Merriam GR. Sex hormones and headache. J Pain Symptom Manag 1993; 8:98.

Huerta-Franco MR, Malacara JM. Association of physical and emotional symptoms with the menstrual cycle and life-style. J Reprod Med 1993; 38: 448–54.

Riley JL III, Robinson ME, Wise EA, Price DD. A meta-analytic review of pain perception across the menstrual cycle. Pain 1999; 81: 225.

LeResche L, Saunders K, Von Korff MR, Barlow W. Use of exogenous hormones and risk of temporomandibular disorder pain. Pain 1997; 69: 153.

Tedford WH, Warren DE, Flynn WE. Alteration of shock aversion thresholds during the menstrual cycle. Percept Psychophys 1977; 21: 193–6.

Goolkasian P. Cyclic changes in pain perception: an ROC analysis. Percept Psychophys 1980; 27: 499.

Dao TT, Knight K, Ton-That V. Modulation of myofascial pain by the reproductive hormones: a preliminary report. The J Prosthet Dent 1998; 79: 663–70.

Hapidou EG, Rollman GB. Menstrual cycle modulation of tender points. Pain 1998; 77: 151.

Sherman JJ, LeResche L, Mancl LA, Huggins K, Sage JC, Dworkin SF. Cyclic effects on experimental pain response in women with temporomandibular disorders. J Orofac Pain 2005; 19: 133–43.

Berman SM, Naliboff BD, Suyenobu B, et al. Sex differences in regional brain response to aversive pelvic visceral stimuli. Am J Physiol 2006; 60: R268–R76.

Berman S, Munakata J, Naliboff BD, Chang L, Mandelkern M, Silverman D. Gender differences in regional brain response to visceral pressure in IBS patients. Eur J Pain 2000; 4: 157.

Moulton EA, Keaser ML, Guliapalli RP, Maitra R, Greenspan JD. Sex differences in the cerebral BOLD signal response to painful heat stimuli. Am J Physiol 2006; 60: R257–R67.

Kern MK, Jaradeh S, Arndorfer RC, Jesmanowicz A, Hyde J, Shaker R. Gender differences in cortical representation of rectal distension in healthy humans. Am J Physiol 2001; 281: G1512–G23.

Derbyshire SWG, Nichols TE, Firestone L, Townsend DW, Jones AKP. Gender differences in patterns of cerebral activation during equal experience of painful laser stimulation. J Pain 2002; 3: 401.

Vincent K, Warnaby C, Stagg CJ, Moore J, Kennedy S, Tracey I. Brain imaging reveals that engagement of descending inhibitory pain pathways in healthy women in a low endogenous estradiol state varies with testosterone. Pain 2013; 154: 515–24.

Blomqvist A. Sex hormones and pain: a new role for brain aromatase? J. Comp. Neurol. 423 (2000) 549–51.

Aloisi AM, Ceccarelli І, Fiorenzani Р, De Padova AM, Massafra C. Testosterone affects formalin-induced responses differently in male and female rats, Neurosci. Lett. 361 (2004) 262–64.

Gaumond I, Arsenault P, Marchand S. Specificity of female and male sex hormones on excitatory and inhibitory phases of formalin-induced nociceptive responses, Brain Res. 1052 (2005) 105–11.

Stoffel EC, Ulibarri CM, Folk JE, Rice KC, Craft RM. Gonadal hormonemodulation of mu, kappa, and delta opioid antinociception in male and female rats, J. Pain 6 (2005) 261–74.

Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses, Neurosci. Biobehav. Rev. 24 (2000) 485–501.

Aloisi AM, Ceccarelli І, Fiorenzani Р. Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats, Ann. N. Y. Acad. Sci. 1007 (2003) 232–7.

Sternberg WF, Mogil JS, Kest B, Page GG, Leong Y, Yam V, et al. Neonatal testosterone exposure influences neurochemistry of non-opioid swim stress-induced analgesia in adult mice, Pain 63 (1995) 321–6.

Berkley KJ. Sex differences in pain. Behav Brain Sci 1997;20:371– 80.

Unruh AM. Gender variations in clinical pain experience. Pain 1996;65:123–67.

Hargreaves R. New migraine and pain research. Headache 2007; 47:S26–43.

Aloisi AM, Bachiocco V, Costantino A, et al. Cross-sex hormone administration changes pain in transsexual women and men. Pain 2007;132:S60–7.

Procacci P, Buzzelli G, Passeri I, et al. Studies on the cutaneous pricking pain threshold in man. Circadian and circatrigintan changes. Res Clin Stud Headache 1970;3:260–76.

Tedford WHJ, Warren DE, Flynn WE. Alteration of shock aversion threshold during the menstrual cycle. Percept Psychophys 1977; 21:193–6.

Brincat M, Moniz CF, Kabalan S, et al. In skin collagen content and metacarpal index after the menopause and its prevention with sex hormone replacement. Br J Obstet Gynaecol 1987;94:126–9.

LeResche L, Saunders K, Von Korff MR, et al. Use of exogenous hormones and risk of temporomandibular disorder pain. Pain 1997;69:153–60.

Brandes JL. The influence of estrogen on migraine: a systematic review. JAMA 2006;295:1824–30.

Martin VT, Lipton RB. Epidemiology and biology of menstrual migraine. Headache 2008;48:S124–30.

Cassidy EM, Tomkins E, Sharifi N, et al. Differing central amine receptor sensitivity in different migraine subtypes? A neuroendocrine study using buspirone. Pain 2003;101:283–90.

Hayashi T, Yamada K, Esaki T, et al. Effect of estrogen on isoforms of nitric oxide synthase: possible mechanism of anti-atheroscle- rotic effect of estrogen. Gerontology 1997;43:24–34.

Levine JD, Taiwo YO. Beta-estradiol induced catecholamine-sensitive hyperalgesia: a contribution to pain in Raynaud’s phenomenon. Brain Res 1989;487:143–7.

Calderone KL. The influence of gender on the frequency of pain and sedative medication administered to postoperative patients. Sex Roles 1990; 23: 713–25.

Leresche L. Defining gender disparities in pain management. Clin Orthop Relat Res 2011; 469: 1871–7.

Weisse CS, Sorum PC, Sanders KN, Syat BL. Do gender and race affect decisions about pain management? J General Inter Med 2001; 16: 211.

Alqudah AF, Hirsh AT, Stutts LA, Scipio CD, Robinson ME. Sex and race differences in rating others’ pain, pain-related negative mood, pain coping, and recommending medical help. J Cyber Ther Rehabil 2010; 3: 63–70.

Wandner LD, Stutts LA, Alqudah AF, et al. Virtual human technology: patient demographics and healthcare training factors in pain observation and treatment recommendations. J Pain Res 2010; 3: 241–7.

Hirsh AT, George SZ, Robinson ME. Pain assessment and treatment disparities: a virtual human technology investigation. Pain 2009; 143: 106–13.

Hillary D. White, Thomas D. Robinson A novel use for testosterone to treat central sensitization of chronic pain in fibromyalgia patients. Int Immunopharm 2015; 27: 244–8.

Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 2004:44:499–523.

Soldin OP, Chung SH, Mattison DR. Sex differences in drug disposition. J Biomed Biotechnol 2011; doi: 10.1155/2011/187103. Epub 2011 Feb 23.

Nicolson TJ, Mellor HR, Roberts RR. Gender differences in drug toxicity. Trends Pharmacol Sci 2010;31(3):108–14.

Anderson GD. Gender differences in pharmacological response. Int Rev Neurobiol 2008;83:1–10.

Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol Res 2007; 55: 81–95.

Chen, M. L. 2000. Gender-related differences in drug pharmacokinetics: Do they translate into clinical outcome? Report to the FDA Office of Women’s Health.

Dominick KL, Ahern FM, Gold CH, Heller DA. Gender differences in NSAID use among older adults with osteoarthritis. Ann Pharmacother. 2003 Nov;37(11):1566–71.

Bäckryd E. Gender differences in dispensed analgesics in Sweden during 2006–2015 – an observational, nationwide, whole-population study. Int J Womens Health. 2018 Jan 18;10:55–64.

Sunil Nikose, Mridul Arora, Pradeep Singh, Devashree Nikose, Swapnil V Gadge and Sohael Khan Gastrointestinal Adverse Effects due to Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Non-Traumatic Painful Musculoskeletal Disorders J Gastrointest Dig Syst 2015, 5:6.

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How to Cite
Ostrovska KO. Gender aspects of the pain syndrome. PMJUA [Internet]. 2019Apr.29 [cited 2019Jun.25];4(1):50-. Available from: