Women and Estrogen and Prevalence in Temporomandibular Disorders

Women and Estrogen and Prevalence in Temporomandibular Disorders

I have a very strong interest in better understanding the potential causes of erosion to the condylar head of the Temporomandibular Joint, either unilateral or bilateral. As we know, this can happen to young females premenstrual and can be a sign of Idiopathic Condylar Resorption, Rheumatoid Arthritis, or early onset of Degenerative Joint Disease. I also feel I am seeing this in my roughly mid-60s-year-old females as well, post menopause, some on Hormone replacement therapy, estrogen patches, etc.  We know there are estrogen receptors in the TM Joints and, as a result, that can be a driver for females to suffer from TMD more frequently than men. 

Researchers have found estrogen may influence pain receptors, which may highlight the differences between male-female TMD-related pain. Fluctuation of estrogen levels occurs before puberty, during menstruation, and after menopause, all of which may impact a woman’s pain threshold. Subsequently, pain onset occurs after puberty and peaks in reproductive years, but tapers after menopause. Evidence suggests that estrogen inhibits inflammatory processes associated with TMD-related pain. During periods of high estrogen concentration levels, the inflammatory process is inhibited and TMD-related pain decreases. Contrastingly, during the menstrual cycle, post-menopause, and following an ovariectomy, low levels of estrogen occur; consequently, lower levels of estrogen induce pro-inflammatory effects within the TMJ, resulting in higher pain levels. 

Although TMD pain varies throughout the menstrual cycle, it is the highest immediately before menses, due to low estrogen levels. Low levels of estrogen are also present in post-menopausal women, which coincides with an increase in TMD-related pain. 

Researchers found estrogen elevates sodium channel plasma, contributing to increased nociception and hyperalgesia, suggesting that the presence of estrogen may lead to TMD-related pain. 

Research shows that higher levels of ERα expression could indicate more inflammation and that lower levels of ERβ expression may also lead to increased inflammation. Within the synovium of the TMJ, estrogen acts on the central nervous system to regulate the inflammatory process. Inflammation of the synovium may lead to inadequate lubrication and nourishment of the cartilage and disc. This is one of the huge values of knowing and using the Rocabado Pain Map I teach during my TMD Course. This pain map allows you to discern which if any synovial tissue is inflamed and then provide the appropriate treatment or possibly an indication for ordering a cone beam scan to see if there is any active inflammation causing erosion of the condylar head. It can help to be preventative as well, meaning trying to catch these inflamed synovial tissues early and hoping to intervene before things get worse. 

Taken together, the studies suggest that estrogen may have a biphasic effect on TMD with high and fluctuating levels promoting certain types of TMD and with low levels potentiating other kinds of TMD. 

Other recent studies have shown that TMD pain is reduced when estrogen levels are high. During pregnancy, there is a dramatic increase in estrogen levels. In one study, the prevalence of TMD was 2–3 lower in pregnant versus nonpregnant age-matched females. Further, in two longitudinal studies, it was shown that reported orofacial pain diminished significantly during the third trimester of pregnancy and increased post-partum, suggesting that TMD-related pain is reduced at high estrogen levels. One possible explanation for discordant results between pregnancy and hormone replacement is an altered sensitivity of tissue to fluctuating estrogen levels, rather than low or high concentrations. 

At this time, we have no definitive answers to how estrogen signaling promotes TMD in females. However, there are four theories to explain the observed effects.  

1. Fluctuations in estrogen levels promote TMD pain. Similar to TMD, the prevalence of migraines without aura is greater in females than in males but not at all ages. Before puberty, the prevalence of migraines is similar between the sexes. However, after puberty, migraines are 2–4 times more likely to occur in females than age-matched males with the peak prevalence occurring in women between the ages of 35–45. The estrogen withdrawal hypothesis suggests that fluctuating estrogen levels pre- and post-menstrual cycles and during peri-menopause predispose women to migraines. Therefore, a similar mechanism may occur in TMD, whereby TMJ pathology may be similar in the sexes but fluctuating levels of estrogen make women more likely to experience longer-lasting pain.  
2. Estrogen protects the TMJ from degeneration and conversely, low levels of estrogen predispose post-menopausal women to TMJ-DD. The vast majority of studies have shown that women over the age of 50 are more likely than age-matched men to suffer from TMJ-DD ( Disc Disorders).  
3. Sex differences in estrogen signaling are contributing to TMD symptoms. ERβ signaling inhibits TMJ growth in female but not in male mice. Taken together, ERβ and/or a hypothalamus ERα negative signaling pathway may cause inhibition of TMJ repair making women more prone to TMD.  
4. Lastly, differences in TMJ anatomy and structure may result in altered biomechanics that predispose the female joint to more mechanical fatigue. The male condyle is larger than the female, on average, and exhibits a longer condylar lingual length with long elliptical condyles compared to the smaller, round condyles of a female TMJ. These anatomical differences result in sex differences in joint loading. Static and dynamic mechanical analyses of aged male and female articular fibrocartilage-subchondral bone units resulted in significant differences in energy dissipation and load to the tissues. In males, the subchondral bone withstands the majority of load whereas in females, the articular fibrocartilage bears a significant proportion of the load. Dynamic stereometry assessment using Magnetic resonance (MR), and cone-beam computed tomography (CBCT) data were used to illustrate an increased energy density in the TMJ of female subjects suggesting an increase in biomechanical fatigue compared to males. 

It remains frustrating that we do not have better, consistent information or knowledge about estrogen and its role in Temporomandibular Disorders. It would be interesting to see the potential effects of birth control in the early years or the estrogen patch in later years, if in any way there is any correlation, etc.  

Results suggested that women using a 185 mg annual cumulative estrogen dosage exhibited a 36% increased probability of receiving a referral for TMD-related care. Interestingly, the probability of receiving a referral for TMD-related care escalated to 84% likelihood among women using a 220 mg annual cumulative estrogen dosage. And of course, other studies have refuted this! 

Robinson JL, Johnson PM, Kister K, Yin MT, Chen J, Wadhwa S. Estrogen signaling impacts temporomandibular joint and periodontal disease pathology. Odontology. 2020 Apr;108(2):153-165.