Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 2012 2024-03-04 15:29:23 |
2 Reference format revised. + 3 word(s) 2015 2024-03-05 02:08:00 | |
3 rollback to version 1 -3 word(s) 2012 2024-03-11 10:05:13 | |
4 Reference format revised. Meta information modification 2012 2024-03-11 10:11:06 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Godley, F.; Meitzen, J.; Nahman-Averbuch, H.; O’neal, M.A.; Yeomans, D.; Santoro, N.; Riggins, N.; Edvinsson, L. Effect of Sex Hormones on Migraine. Encyclopedia. Available online: (accessed on 21 April 2024).
Godley F, Meitzen J, Nahman-Averbuch H, O’neal MA, Yeomans D, Santoro N, et al. Effect of Sex Hormones on Migraine. Encyclopedia. Available at: Accessed April 21, 2024.
Godley, Frederick, John Meitzen, Hadas Nahman-Averbuch, Mary Angela O’neal, David Yeomans, Nanette Santoro, Nina Riggins, Lars Edvinsson. "Effect of Sex Hormones on Migraine" Encyclopedia, (accessed April 21, 2024).
Godley, F., Meitzen, J., Nahman-Averbuch, H., O’neal, M.A., Yeomans, D., Santoro, N., Riggins, N., & Edvinsson, L. (2024, March 04). Effect of Sex Hormones on Migraine. In Encyclopedia.
Godley, Frederick, et al. "Effect of Sex Hormones on Migraine." Encyclopedia. Web. 04 March, 2024.
Effect of Sex Hormones on Migraine

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin.

sex hormones migraine estrogen oxytocin progesterone testosterone prolactin vasopressin

1. Sex Hormone Fluctuation as a Trigger of Migraine

Migraine tends to follow a classic temporal pattern throughout a cisgender woman’s life that corresponds with sex hormone fluctuations during reproductive milestones in the female lifespan. Puberty is a key period with significant changes in sex hormone levels. Interestingly, in children and adolescents, the prevalence of migraine headaches is nearly equivalent in boys and girls [1], but during puberty, the prevalence of migraine between men and women diverges and is 3–4 times higher in women compared to men [2][3]. This sex difference corresponds to the onset of menarche and falls after menopause.
Migraine symptoms can be linked to menstrual cycle changes (menstrual migraine) and 18–25% of women with migraine experience migraine or headaches during menstruation [4]. Menstrual migraine can be associated with a higher frequency of migraine-accompanying symptoms and more frequent and severe migraine attacks [5]. A comparison of women with and without migraine shows that those with migraine are characterized by faster late-luteal-phase estrogen decline compared to women without migraine. Thus, the timing and rate of estrogen withdrawal has been proposed to be a marker of vulnerability to migraine in women [6]. Contraceptive pills reduce the number of migraine attacks, migraine days, pain scores, disability scores, and migraine medication use while reducing the frequency of aura, and lowering, but not eliminating, the risks of cardiovascular complications or other side effects [7][8][9]. Another strategy is to use estrogen supplementation with a pill, vaginal gel or patch during the menstrual week.
Migraine is a heterogeneous disease associated with many possible combinations of genetic defects which share a common phenotype of intermittent pain or other hypersensitivities. This accounts for the unpredictable response of migraineurs to medications and the effect of hormones on the nociceptive system is no exception. 
Migraine disease has a complex relationship with pregnancy. For 8% of women with migraine, their headaches worsen during the first trimester. This is especially true for migraine without aura, which is more hormonally driven [10][11][12]. The majority of women with migraine generally experience reduced migraine symptoms by the third trimester [13]. However, many women have the acute onset of headaches during pregnancy. 
Perimenopause, the period of two to eight years when menses first become irregular prior to the year after the end of menses, is a time when hormonal fluctuations are still occurring, and pre-existing migraine symptoms can remain unchanged, improve, or worsen [14][15][16]. In total, 8–13% of women report their first migraine during perimenopause [17][18]. However, many women see a decrease in headache prevalence during this period [19][20], most prominently in women who already suffer from migraine with aura [21]. For unexplained reasons, mid-facial pain and pressure and vestibular migraine can become prominent symptoms during perimenopause and menopause [22]. Hormone replacement therapy, or menopause replacement therapy (MRT), usually a continuous dosing of estrogen alone or estrogen plus progestin (ethinyl estradiol 5 µg combined with norethindrone acetate 1 mg, estradiol 1 mg combined with 0.5 mg norethindrone acetate, or transdermal estradiol combined with one-quarter or one-half of a 5 mg norethindrone daily) [23], remains an option, particularly for those women who have not had a hysterectomy because estrogen alone increases the risk of endometrial cancer. Transdermal estrogen patches or gels can be efficacious and less risky than systemic estrogen replacement in treating migraine [4][16][24].
The bottom line is that current sex hormone supplements play a valuable role in mitigating the symptoms of migraine, but, because they are still associated with serious complications, especially migraine with aura, and exacerbate migraine symptoms in some, many medical professionals choose not to use hormone supplements in their migraine treatment plan. For example, plant-derived hormones (phytoestrogens) and the derivative bio-identical hormones are effective in reducing menstrual-related migraine headaches [25], but there is no rigorous scientific evidence that these supplements are safer or more natural compared to the current hormonal interventions. Phytoestrogen-containing foods, such as soy, are recommended over supplements, and all phytoestrogens should be avoided if there is a chance of pregnancy because these compounds might adversely affect the endocrine system. It is speculated that they might be safer in older women, such as those suffering from menopausal symptoms, particularly hot flashes [26][27], but currently there is not enough evidence to conclude that the benefits of phytoestrogens outweigh their potential health risks [28], and they do not appear to be ideal migraine preventive agents. Thus, since many women with migraine are unable to find an effective preventive therapy, there remains the challenge to understand how sex hormone supplements work, with the goal that select metabolites or synthetic derivatives might be both efficacious and safer than current hormonal therapies.

2. Which Sex Hormones Should Be the Target?

2.1. Estrogen

Estrogen plays a complicated role in migraine disease. Both drops and fluctuations in estrogen are associated with migraine symptoms, but its effect varies between individuals because of different receptors, metabolites, and interactions with other hormones. The dominant understanding of how crucial estrogen is in protecting individuals from migraine symptoms is what happens when estrogen levels decline: the estrogen withdrawal hypothesis. This hypothesis theorizes that drops in plasma estrogen trigger migraine attacks and neuroinflammation, eventually leading to chronic sensitization [29]. There are several possible mechanisms to explain his theory. One explanation is that estrogen suppresses pain by binding to estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta), which are primarily associated with cell nuclei in the trigeminal ganglia. Activation of these nuclear receptors regulates inflammatory genes that ultimately suppresses cell excitability [30].

CGRP is believed to be among the critical neuropeptides responsible for the throbbing pain associated with a migraine attack and the neuroinflammation that causes both pain and that perhaps cause neuroplastic neural changes responsible for chronic central sensitization [31]. Specifically, estrogen may also increase neurogenic vasodilation and gene regulation.
While the estrogen withdrawal hypothesis focuses primarily on the trigeminal nerves, it is important to recognize the wider-ranging actions of estrogen in other parts of the body and brain [32]. A second mechanism to explain the estrogen withdrawal theory was demonstrated in an animal model where reduced levels of estrogen were shown to increase the frequency of cortical spreading depressions, the electrophysiological event believed to be responsible for triggering the trigeminal system and headaches, as well as auras [33].

2.2. Progesterone

Progesterone, the second major sex hormone, is produced in the ovaries, adrenal glands and placenta, and primarily helps maintain pregnancy. Progesterone with estradiol is found at the onset of menstrual migraines. Nonetheless, it is more likely that the withdrawal of estradiol, rather than progesterone, initiates migraine headaches. Instead, progesterone appears to protect neurons by suppressing neuroinflammation and reducing trigeminal nerve sensitivity.
It may be in the interplay with additional factors where progesterone plays an integral role in pain modulation. In a longitudinal study of fibromyalgia, it was high levels of progesterone and testosterone together that were associated with less pain [34]. Progesterone and testosterone are able to penetrate the blood-brain barrier and function as precursors for neurosteroids. There is an example of a progesterone derivative which enhances GABA function by modulating GABA receptors and, in turn, inhibits neuronal sensitivity [35][36].
Currently, synthetic progesterone is used as a form of birth control and a migraine preventive agent in the form of a continuous low dose of progestin. Bio-identical progesterone can be delivered in three formulations: orally, topically, and as a suppository. Progesterone may improve insomnia as a mild sedative, and improve sleep apneas by stimulating respiration [37].

2.3. Testosterone

A popular belief is that testosterone is the male hormone whereas estrogen is the female hormone. However, this is an oversimplification, as both estrogen and testosterone have important roles to play in individuals of either sex [38]. In both males and females, the balance between estrogen and testosterone production throughout life influences the function of both reproductive and nonreproductive organs [38].
Testosterone could be a potential therapeutic target, as it has an antinociceptive effect [39][40][41][42][43]. In animal studies, after gonadectomy or the blocking of testosterone receptors, animals appeared more sensitive to nociceptive stimuli [44][45][46][47][48]. The few human studies performed support an analgesic effect of testosterone, as higher testosterone levels are associated with lower experimental pain sensitivity [49]. Studies on the relationship of testosterone to migraine are few. Testosterone levels are lower in adults with migraine vs. without migraine, and are related to migraine severity. Interestingly, even when similar testosterone levels are found, men with migraine more frequently report symptoms of androgen deficiency compared to men with no migraine. However, one study found that no differences in testosterone levels were found in women with vs. without migraine, and that migraine pain intensity was not correlated with testosterone levels. 
Testosterone appears to be able to effectively reduce symptoms by suppressing spreading depressions, increasing serotonin, stabilizing cerebral blood flow, and reducing cell excitability and neuroinflammation [50]. These metabolic effects may explain the findings that testosterone treatment can improve clinical pain and experimental pain sensitivity in patients with chronic pain, including in patients with temporomandibular joint pain, fibromyalgia, and migraine [51][52][53][54], and that testosterone treatment delivered by a subcutaneous implant significantly reduces migraine intensity [53]

2.4. Oxytocin

Oxytocin’s (OT) therapeutic effects in migraine are complex and widespread in the nervous system, including at the level of the primary sensory neuron, spinal cord, and in a variety of brain regions associated with pain processing and modulation [55][56][57].
The effect of OT on migraine has been shown via a case report in which intravenous OT provided analgesia and migraine relief [58]. In addition, double-blind, placebo-controlled clinical studies have shown evidence that intranasal OT sprays are efficacious for treating migraine pain in adult men and women [55][59] and experimental-evoked pain in men [60]. A benefit of oxytocin as a treatment for migraine is that it is routinely administered intranasally for inducing labor, postpartum care, and for enhancing lactation, and its safety profile is well documented. In addition, intranasal oxytocin in humans has no major side effects [61].
OT is a neuropeptide that exerts its pain-inhibitory effects both at the level of the primary afferent fiber and in the central nervous system. The first mechanism is via the descending neural pathway from the paraventricular nucleus (PVN) to the dorsal horn of the spinal cord [62][63]. Signals from the PVN release oxytocin in the spinal dorsal horn that activate GABAergic interneurons in the dorsal horn which secondarily recruit other inhibitory GABAergic interneurons and suppress pain signals carried by ascending A-delta and C-fibers [64][65][66][67]. The second mechanism is where OT released from the supraoptic nucleus (SON) in the hypothalamus, periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and the spinal dorsal horn [68][69] modulates central endogenous pain pathways by raising nociceptive thresholds [70][71]
OTR mRNA and proteins are expressed in nociceptive C-fibers and Aδ-fibers in the adult rat trigeminal ganglia [72], and have a high level of co-expression with CGRP in trigeminal ganglia neurons [55]. OT dose-dependently blocks the release of calcitonin gene-related peptide (CGRP) from trigeminal afferent neurons innervating the dura in vitro [72]

2.5. Vasopressin

Arginine vasopressin (AVP) is a neuropeptide hormone that has an antidiuretic effect in low concentrations, but at higher concentrations it causes vasoconstriction. Together, these effects raise blood pressure. AVP also has a role in pain, behavior, platelet aggregation, and blood coagulation functions.
Much of AVP is synthesized in the SON of the hypothalamus and, while AVP is largely stored in and secreted from the pituitary, AVP-containing hypothalamic fibers are widely distributed in the CNS [73]. These fibers reach different centers in the brainstem and, in particular, the trigemminal nuclei. The AVP receptors (VP1 and VP2) are found in the trigeminal ganglion [72]

2.6. Prolactin

Prolactin (PRL) is a hormone that is responsible for lactation, breast development, and hundreds of other actions needed to maintain homeostasis. PRL is chemically related to growth hormones and placental lactogen hormones. In an animal model, high levels of prolactin increased meningeal trigeminal pain sensitivity by only affecting CGRP in female rodents [74]


  1. Szperka, C. Headache in Children and Adolescents. Continuum 2021, 27, 703–731.
  2. Tonini, M.C. Gender differences in migraine. Neurol. Sci. 2018, 39, 77–78.
  3. Vetvik, K.G.; MacGregor, E.A. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017, 16, 76–87.
  4. MacGregor, E.A.; Frith, A.; Ellis, J.; Aspinall, L.; Hackshaw, A. Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen. Neurology 2006, 67, 2154–2158.
  5. Chalmer, M.A.; Kogelman, L.J.A.; Ullum, H.; Sørensen, E.; Didriksen, M.; Mikkelsen, S.; Dinh, K.M.; Brodersen, T.; Nielsen, K.R.; Bruun, M.T.; et al. Population-Based Characterization of Menstrual Migraine and Proposed Diagnostic Criteria. JAMA Netw. Open 2023, 6, e2313235.
  6. Pavlović, J.M.; Allshouse, A.A.; Santoro, N.F.; Crawford, S.L.; Thurston, R.C.; Neal-Perry, G.S.; Lipton, R.B.; Derby, C.A. Sex hormones in women with and without migraine: Evidence of migraine-specific hormone profiles. Neurology 2016, 87, 49–56.
  7. Calhoun, A.H.; Batur, P. Combined hormonal contraceptives and migraine: An update on the evidence. Clevel. Clin. J. Med. 2017, 84, 631–638.
  8. Warhurst, S.; Rofe, C.J.; Brew, B.J.; Bateson, D.; McGeechan, K.; Merki-Feld, G.S.; Garrick, R.; Tomlinson, S.E. Effectiveness of the progestin-only pill for migraine treatment in women: A systematic review and meta-analysis. Cephalalgia 2018, 38, 754–764.
  9. Lyall, M.; de Oliveira, B.R.; Mody, S.K. Considerations for Contraceptive Use Among Patients with Migraines. Curr. Obstet. Gynecol. Rep. 2023, 12, 57–63.
  10. Aubé, M. Migraine in pregnancy. Neurology 1999, 53 (Suppl. S1), S26–S28.
  11. Ertresvåg, J.M.; Zwart, J.A.; Helde, G.; Johnsen, H.J.; Bovim, G. Headache and transient focal neurological symptoms during pregnancy, a prospective cohort. Acta Neurol. Scand. 2005, 111, 233–237.
  12. Kvisvik, E.V.; Stovner, L.J.; Helde, G.; Bovim, G.; Linde, M. Headache and migraine during pregnancy and puerperium: The MIGRA-study. J. Headache Pain 2011, 12, 443–451.
  13. Goadsby, P.J.; Goldberg, J.; Silberstein, S.D. Migraine in pregnancy. BMJ 2008, 336, 1502–1504.
  14. Mueller, L. Predictability of exogenous hormone effect on subgroups of migraineurs. Headache 2000, 40, 189–193.
  15. Hodson, J.; Thompson, J.; Al-Azzawi, F. Headache at menopause and in hormone replacement therapy users. Climacteric J. Int. Menopause Soc. 2000, 3, 119–124.
  16. Ibrahimi, K.; Couturier, E.G.M.; MaassenVanDenBrink, A. Migraine and perimenopause. Maturitas 2014, 78, 277–280.
  17. Granella, F.; Sances, G.; Zanferrari, C.; Costa, A.; Martignoni, E.; Manzoni, G.C. Migraine without aura and reproductive life events: A clinical epidemiological study in 1300 women. Headache 1993, 33, 385–389.
  18. Cupini, L.M.; Matteis, M.; Troisi, E.; Calabresi, P.; Bernardi, G.; Silvestrini, M. Sex-hormone-related events in migrainous females. A clinical comparative study between migraine with aura and migraine without aura. Cephalalgia 1995, 15, 140–144.
  19. Wang, S.J.; Fuh, J.L.; Lu, S.R.; Juang, K.D.; Wang, P.H. Migraine prevalence during menopausal transition. Headache 2003, 43, 470–478.
  20. Freeman, E.W.; Sammel, M.D.; Lin, H.; Gracia, C.R.; Kapoor, S. Symptoms in the menopausal transition: Hormone and behavioral correlates. Obstet. Gynecol. 2008, 111, 127–136.
  21. Mattsson, P. Hormonal factors in migraine: A population-based study of women aged 40 to 74 years. Headache 2003, 43, 27–35.
  22. Park, J.H.; Viirre, E. Vestibular migraine may be an important cause of dizziness/vertigo in perimenopausal period. Med. Hypotheses 2010, 75, 409–414.
  23. Pavlović, J.M. Evaluation and management of migraine in midlife women. Menopause 2018, 25, 927–929.
  24. Kaiser, H.J.; Meienberg, O. Deterioration or onset of migraine under oestrogen replacement therapy in the menopause. J. Neurol. 1993, 240, 195–196.
  25. Burke, B.E.; Olson, R.D.; Cusack, B.J. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed. Pharmacother. 2002, 56, 283–288.
  26. Patisaul, H.B.; Jefferson, W. The pros and cons of phytoestrogens. Front. Neuroendocrinol. 2010, 31, 400–419.
  27. Chen, M.N.; Lin, C.C.; Liu, C.F. Efficacy of phytoestrogens for menopausal symptoms: A meta-analysis and systematic review. Climacteric 2015, 18, 260–269.
  28. Rietjens, I.M.C.M.; Louisse, J.; Beekmann, K. The potential health effects of dietary phytoestrogens. Br. J. Pharmacol. 2017, 174, 1263–1280.
  29. Sarajari, S.; Oblinger, M.M. Estrogen Effects on Pain Sensitivity and Neuropeptide Expression in Rat Sensory Neurons. Exp. Neurol. 2010, 224, 163–169.
  30. Welch, K.M.A.; Brandes, J.L.; Berman, N.E.J. Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. Neurol. Sci. 2006, 27 (Suppl. S2), S190–S192.
  31. Wattiez, A.S.; Sowers, L.P.; Russo, A.F. Calcitonin gene-related peptide (CGRP): Role in migraine pathophysiology and therapeutic targeting. Expert Opin. Ther. Targets 2020, 24, 91–100.
  32. Rettberg, J.R.; Yao, J.; Brinton, R.D. Estrogen: A master regulator of bioenergetic systems in the brain and body. Front. Neuroendocrinol. 2014, 35, 8–30.
  33. Kudo, C.; Harriott, A.M.; Moskowitz, M.A.; Waeber, C.; Ayata, C. Estrogen modulation of cortical spreading depression. J. Headache Pain 2023, 24, 62.
  34. Schertzinger, M.; Wesson-Sides, K.; Parkitny, L.; Younger, J. Daily Fluctuations of Progesterone and Testosterone Are Associated with Fibromyalgia Pain Severity. J. Pain 2018, 19, 410–417.
  35. Chuang, S.H.; Reddy, D.S. 3β-Methyl-Neurosteroid Analogs Are Preferential Positive Allosteric Modulators and Direct Activators of Extrasynaptic δ-Subunit γ-Aminobutyric Acid Type A Receptors in the Hippocampus Dentate Gyrus Subfield. J. Pharmacol. Exp. Ther. 2018, 365, 583–601.
  36. Reddy, D.S. Neurosteroids: Endogenous role in the human brain and therapeutic potentials. Prog. Brain Res. 2010, 186, 113–137.
  37. Andersen, M.L.; Bittencourt, L.R.A.; Antunes, B.I.; Tufik, S. Effects of Progesterone on Sleep: A Possible Pharmacological Treatment for Sleep-Breathing Disorders? CMC 2006, 13, 3575–3582.
  38. Simpson, E.R. Sources of estrogen and their importance. J. Steroid Biochem. Mol. Biol. 2003, 86, 225–230.
  39. Bartley, E.J.; Palit, S.; Kuhn, B.L.; Kerr, K.L.; Terry, E.L.; DelVentura, J.L.; Rhudy, J.L. Nociceptive processing in women with premenstrual dysphoric disorder (PMDD): The role of menstrual phase and sex hormones. Clin. J. Pain 2015, 31, 304–314.
  40. Bartley, E.J.; Palit, S.; Kuhn, B.L.; Kerr, K.L.; Terry, E.L.; DelVentura, J.L.; Rhudy, J.L. Natural variation in testosterone is associated with hypoalgesia in healthy women. Clin. J. Pain 2015, 31, 730–739.
  41. Choi, J.C.; Park, Y.H.; Park, S.K.; Lee, J.S.; Kim, J.; Choi, J.I.; Yoon, K.B.; Lee, S.; Lim, D.E.; Choi, J.Y.; et al. Testosterone effects on pain and brain activation patterns. Acta Anaesthesiol. Scand. 2017, 61, 668–675.
  42. Choi, J.C.; Chung, M.I.; Lee, Y.D. Modulation of pain sensation by stress-related testosterone and cortisol. Anaesthesia 2012, 67, 1146–1151.
  43. Teepker, M.; Peters, M.; Vedder, H.; Schepelmann, K.; Lautenbacher, S. Menstrual variation in experimental pain: Correlation with gonadal hormones. Neuropsychobiology 2010, 61, 131–140.
  44. Aloisi, A.M.; Ceccarelli, I.; Fiorenzani, P. Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats. Ann. N. Y. Acad. Sci. 2003, 1007, 232–237.
  45. Ceccarelli, I.; Scaramuzzino, A.; Massafra, C.; Aloisi, A.M. The behavioral and neuronal effects induced by repetitive nociceptive stimulation are affected by gonadal hormones in male rats. Pain 2003, 104, 35–47.
  46. 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. 2005, 1052, 105–111.
  47. Aloisi, A.M.; Ceccarelli, I.; Fiorenzani, P.; De Padova, A.M.; Massafra, C. Testosterone affects formalin-induced responses differently in male and female rats. Neurosci. Lett. 2004, 361, 262–264.
  48. Stoffel, E.C.; Ulibarri, C.M.; Craft, R.M. Gonadal steroid hormone modulation of nociception, morphine antinociception and reproductive indices in male and female rats. Pain 2003, 103, 285–302.
  49. Basaria, S.; Travison, T.G.; Alford, D.; Knapp, P.E.; Teeter, K.; Cahalan, C.; Eder, R.; Lakshman, K.; Bachman, E.; Mensing, G.; et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency: A randomized controlled trial. Pain 2015, 156, 280–288.
  50. Ahmad, A.H.; Ismail, Z. c-fos and its Consequences in Pain. Malays. J. Med. Sci. 2002, 9, 3–8.
  51. White, H.D.; Brown, L.A.J.; Gyurik, R.J.; Manganiello, P.D.; Robinson, T.D.; Hallock, L.S.; Lewis, L.D.; Yeo, Y.-T.J. Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response. Int. Immunopharmacol. 2015, 27, 249–256.
  52. Fischer, L.; Clemente, J.T.; Tambeli, C.H. The protective role of testosterone in the development of temporomandibular joint pain. J. Pain 2007, 8, 437–442.
  53. Glaser, R.; Dimitrakakis, C.; Trimble, N.; Martin, V. Testosterone pellet implants and migraine headaches: A pilot study. Maturitas 2012, 71, 385–388.
  54. English, K.M.; Steeds, R.P.; Jones, T.H.; Diver, M.J.; Channer, K.S. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation 2000, 102, 1906–1911.
  55. Tzabazis, A.; Kori, S.; Mechanic, J.; Miller, J.; Pascual, C.; Manering, N.; Carson, D.; Klukinov, M.; Spierings, E.; Jacobs, D.; et al. Oxytocin and Migraine Headache. Headache 2017, 57 (Suppl. S2), 64–75.
  56. Rash, J.A.; Aguirre-Camacho, A.; Campbell, T.S. Oxytocin and pain: A systematic review and synthesis of findings. Clin. J. Pain 2014, 30, 453–462.
  57. Shamay-Tsoory, S.G.; Abu-Akel, A. The Social Salience Hypothesis of Oxytocin. Biol. Psychiatry 2016, 79, 194–202.
  58. Phillips, W.J.; Ostrovsky, O.; Galli, R.L.; Dickey, S. Relief of acute migraine headache with intravenous oxytocin: Report of two cases. J. Pain Palliat. Care Pharmacother. 2006, 20, 25–28.
  59. Wang, Y.L.; Yuan, Y.; Yang, J.; Wang, C.H.; Pan, Y.J.; Lu, L.; Wu, Y.Q.; Wang, D.X.; Lv, L.X.; Li, R.R.; et al. The interaction between the oxytocin and pain modulation in headache patients. Neuropeptides 2013, 47, 93–97.
  60. Paloyelis, Y.; Krahé, C.; Maltezos, S.; Williams, S.C.; Howard, M.A.; Fotopoulou, A. The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials. J. Neuroendocrinol. 2016, 28.
  61. MacDonald, E.; Dadds, M.R.; Brennan, J.L.; Williams, K.; Levy, F.; Cauchi, A.J. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology 2011, 36, 1114–1126.
  62. Iwasaki, M.; Lefevre, A.; Althammer, F.; Creusot, E.C.; Łąpieś, O.; Petitjean, H.; Hilfiger, L.; Kerspern, D.; Melchior, M.; Küppers, S.; et al. An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats. Nat. Commun. 2023, 14, 1066.
  63. Swanson, L.W.; McKellar, S. The distribution of oxytocin- and neurophysin-stained fibers in the spinal cord of the rat and monkey. J. Comp. Neurol. 1979, 188, 87–106.
  64. Breton, J.D.; Veinante, P.; Uhl-Bronner, S.; Vergnano, A.M.; Freund-Mercier, M.J.; Schlichter, R.; Poisbeau, P. Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition. Mol. Pain 2008, 4, 19.
  65. Rojas-Piloni, G.; López-Hidalgo, M.; Martínez-Lorenzana, G.; Rodríguez-Jiménez, J.; Condés-Lara, M. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation. Brain Res. 2007, 1137, 69–77.
  66. Condés-Lara, M.; González, N.M.; Martínez-Lorenzana, G.; Delgado, O.L.; Freund-Mercier, M.J. Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. Brain Res. 2003, 976, 75–81.
  67. Miranda-Cardenas, Y.; Rojas-Piloni, G.; Martínez-Lorenzana, G.; Rodríguez-Jiménez, J.; López-Hidalgo, M.; Freund-Mercier, M.J.; Condés-Lara, M. Oxytocin and electrical stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects that are reversed by an oxytocin antagonist. Pain 2006, 122, 182–189.
  68. Yang, J.; Liang, J.Y.; Li, P.; Pan, Y.J.; Qiu, P.Y.; Zhang, J.; Hao, F.; Wang, D.X. Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides. Peptides 2011, 32, 1255–1261.
  69. Yang, J.; Li, P.; Liang, J.Y.; Pan, Y.J.; Yan, X.Q.; Yan, F.L.; Hao, F.; Zhang, X.Y.; Zhang, J.; Qiu, P.Y.; et al. Oxytocin in the periaqueductal grey regulates nociception in the rat. Regul. Pept. 2011, 169, 39–42.
  70. Yang, J.; Yang, Y.; Chen, J.M.; Liu, W.Y.; Wang, C.H.; Lin, B.C. Central oxytocin enhances antinociception in the rat. Peptides 2007, 28, 1113–1119.
  71. Yang, J.; Yang, Y.; Chen, J.M.; Liu, W.Y.; Lin, B.C. Investigating the role of the hypothalamic supraoptic nucleus in nociception in the rat. Life Sci. 2008, 82, 166–173.
  72. Warfvinge, K.; Krause, D.N.; Maddahi, A.; Grell, A.-S.; Edvinsson, J.C.A.; Haanes, K.A.; Edvinsson, L. Oxytocin as a regulatory neuropeptide in the trigeminovascular system: Localization, expression and function of oxytocin and oxytocin receptors. Cephalalgia 2020, 40, 1283–1295.
  73. Warfvinge, K.; Krause, D.N.; Maddahi, A.; Edvinsson, J.C.A.; Edvinsson, L.; Haanes, K.A. Estrogen receptors α, β and GPER in the CNS and trigeminal system—Molecular and functional aspects. J. Headache Pain 2020, 21, 131.
  74. Avona, A.; Mason, B.N.; Burgos-Vega, C.; Hovhannisyan, A.H.; Belugin, S.N.; Mecklenburg, J.; Goffin, V.; Wajahat, N.; Price, T.J.; Akopian, A.N.; et al. Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior. Ann. Neurol. 2021, 89, 1129–1144.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , , , ,
View Times: 64
Revisions: 4 times (View History)
Update Date: 11 Mar 2024