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Classification: A

Drug products: Dolatramyl, Gemadol, Nobligan®, Nobligan® retard, Tiparol®, Tiparol® OD, Tiparol® Retard, Tradolan®, Tradolan® Retard, Tramadol 2care4, Tramadol Actavis, Tramadol Alternova, Tramadol Aurobindo, Tramadol HEXAL, Tramadol Krka, Tramadol Retard Actavis, Tramadol Retard Hexal, Tramadol Retard Krka, Tramadol Retard Medartuum, Tramadol Retard Mylan, Tramadol STADA®, Tramadol Vitabalans, Tramuno, Zaldiar

ATC code: N02AJ13, N02AX02

Substances: tramadol, tramadol hydrochloride


Studies show similar effect of tramadol on pain relief in men and women. In an observational study on patients undergoing laparoscopic cholecystectomy, women and men reported the same pain level before tramadol injection. Women reported more pain and received a higher mean dose tramadol during the first postoperative hour. However, the decrease in pain was similar between men and women after 30 minutes.
Tramadol-induced seizures are dose-dependent in a similar way in men and women.

Additional information

The prevalence of several clinical pain conditions is higher in women than in men. Differences in pharmacokinetics, sex hormones, stress response, or socio-cultural aspects may be of importance [1-3]. Therefore, sex and gender differences of pain medications are difficult to interpret [4].

Pharmacokinetics and dosing

A study in healthy Iranian volunteers (12 men, 12 women) showed no differences in pharmacokinetics of a single dose of 100 mg tramadol [5]. The original manufacturer reports that dose-normalized AUC values for tramadol are higher in healthy women than men, but that the results shows considerable overlap in AUC values between men and women. The scientific data backing this statement has not been presented [6].In a prospective observational study in patients undergoing laparoscopic cholecystectomy (60 men, 60 women), mean dose of tramadol was higher in women during the first postoperative hour in order to achieve a similar degree of analgesia (40 mg vs. 27.8 mg). Baseline pain score was similar in men and women. The difference in doses was not significant during the later period [7]. The original manufacturer recommends no dosage adjustment based on patient's sex [6].


The effect of sex on pain perception has been analyzed in a prospective observational study in patients after laparoscopic cholecystectomy (60 men, 60 women). Patients assessed postoperative pain based on a numerical rating score and also indicated the degree of pain improvement after receiving tramadol 10 mg i.v. Baseline pain score was similar in men and women. Women expressed more pain at 20 and 30 min after first tramadol administration and required more tramadol during the first postoperative hour (see Pharmacokinetics and dosing). The decrease in pain was similar in men and women after 30 min postoperatively [7].A randomized, placebo-controlled trial (63 men, 167 women) showed that the analgesic effect of 200 mg tramadol once daily for osteoarthritis was similar in men and women [8].

Adverse effects

No studies on differences between men and women using therapeutic recommended doses have been found. There is a risk of seizure when using high doses of tramadol in both men and women (see Other information).

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

There is a risk of seizure when using high doses of tramadol [9]. An observational study (112 men, 23 women) analyzed the relation between seizure and tramadol intoxication in Iranian patients with a history of tramadol overdose and experience of seizure or loss of consciousness. Seizures correlated with higher reported doses in a similar way in men and women [10]. Another Iranian study (197 men, 35 women), retrospectively analyzed the prevalence, type and site of injuries due to tramadol-induced seizures. The prevalence of trauma was 24.6% and the occurrence of trauma was independent of patient's sex [11].

Updated: 2022-12-22

Date of litterature search: 2015-02-23


  1. Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132 Suppl 1:S26-45. PubMed
  2. Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52-8. PubMed
  3. Sorge RE, Totsch SK. Sex Differences in Pain. J Neurosci Res. 2017;95(6):1271-1281. PubMed
  4. Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
  5. Ardakani YH, Rouini MR. Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers. Biopharm Drug Dispos. 2007;28:527-34. PubMed
  6. Conzip (tramadol hydrochloride). DailyMed [www]. US national Library of Medicine. [updated 2014-10-01, cited 2015-02-23]. länk
  7. Hussain AM, Khan FA, Ahmed A, Chawla T, Azam SI. Effect of gender on pain perception and analgesic consumption in laparoscopic cholecystectomy: An observational study. J Anaesthesiol Clin Pharmacol. 2013;29:337-41. PubMed
  8. Malonne H, Coffiner M, Sonet B, Sereno A, Vanderbist F. Efficacy and tolerability of sustained-release tramadol in the treatment of symptomatic osteoarthritis of the hip or knee: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther. 2004;26:1774-82. PubMed
  9. Nobligan (tramadol). Summary of Product Characteristics. Medical Products Agency Sweden; 2014.
  10. Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC. Factors related to seizure in tramadol poisoning and its blood concentration. J Med Toxicol. 2011;7:183-8. PubMed
  11. Farajidana H, Hassanian-Moghaddam H, Zamani N, Sanaei-Zadeh H. Tramadol-induced seizures and trauma. Eur Rev Med Pharmacol Sci. 2012;16 Suppl 1:34-7. PubMed
  12. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Mia von Euler, Karin Schenck-Gustafsson

Approved by: Karin Schenck-Gustafsson