Table 1.

Sex Hormones in Pain-Related Conditions.

Pain-Related Condition	Major Biochemical Pathways	Main Findings
Headaches	Estrogen CGRP	Biological females are more likely to experience headaches due to the impact of estrogen on the potent vasodilator, CGRP. This is especially prevalent during pregnancy and in biological females receiving estrogen oral contraceptive pills. Male transgender patients receiving hormone replacement therapy experienced more pain than their female transgender counterparts highlighting the impact of sex hormones on pain perception.
Temporomandibular Disorders	Estrogen Neuropeptide Y Galanin mRNA	Biological females are more likely to experience temporomandibular pain prior to estrogen peak and ovulation. Females receiving steady estrogen replacement through oral contraceptives, were less likely to experience pain. Elevated neuropeptide Y and galanin mRNA are also commonly observed, contributing to the impact of estrogen on pain perception.
Fibromyalgia	VMAT-2 Estrogen	Postmenopausal women are more likely to experience pain related to fibromyalgia. Estrogen replacement reduces the pain by 50%, confirming the benefit of steady estrogen levels as opposed to the cyclical pattern. In-utero exposure to female hormones places transgender men at higher risk of fibromyalgia than transgender women patients despite hormone replacement therapy.
Visceral Pain	Estrogen Androgens Testosterone	Lack of estrogen increased stress-induced pain sensitivity while testosterone administration reduced the pain sensitivity, confirming the protective features of male sex hormones. Female hormone replacement increased pain sensitivity suggesting similar results in transgender women patients.
Musculoskeletal Pain	TRPV1 Testosterone	Increased mechanical sensitivity is seen in biological female rats and male rats that are not producing the appropriate testosterone levels. Pain is up regulated by the presence of TRPV1 receptors. Testosterone replacement reduced the pain in males but did not influence the female rats.
Female Reproductive Organs	Estrogen NMDA TRPA1 TRPV1	Estrogen upregulated the expression of NMDA, TRPA1, and TRPV1, and all of which play a role in increasing pain perception and enhancing molecular signaling of pain. Transgender men and women are at risk for breast pain. In transgender men, the physical binding increases their pain levels while in transgender women, the hormone replacement therapy seems to precipitate the pain most likely due to tissue changes.