Hormones & Menopause

Understanding "Burning Mouth Syndrome" in Post-Menopausal Women

Linda M. Bartoshuk, Ph.D., Professor of Surgery

Burning mouth syndrome (BMS), an intense and painful burning sensation in the mouth, occurs predominantly in women after menopause when the incidence rate can be as high as 33 percent. BMS is associated with severe damage to tasting function, often to the part of the tongue that detects bitter tastes. Dr. Bartoshuk’s research on this under-recognized syndrome has led to specific recommendations for treatment.

Highlighted Study Findings

Dr. Bartoshuk suspected that BMS was a sensory phantom (that is, caused by abnormal activation of the part of the brain that recognizes oral pain). Her funded study allowed her to confirm this hypothesis. Two new discoveries emerged from the research, showing that those with BMS had severe taste damage (most typically, they could not taste bitter on the tips of their tongues), and they were also “supertasters,” (individuals born with unusually large numbers of taste buds). To understand why these findings are important, it is helpful to know the sensory system involved in taste. The taste of food activates “taste nerves,” which then carry the sensory information to the brain. In addition to receiving taste input, this same area in the brain is responsible for blocking oral pain. When taste is damaged, this part of the brain no longer inhibits the oral pain. This results in abnormal activity in a specific part of the brain producing oral pain sensations. This type of damage in “supertasters” results in particularly intense BMS. As a result of this work, we now understand why postmenopausal women are at special risk for BMS. First, women are more likely than are men to be “supertasters.” Second, the ability to taste bitter, which functions as a poison detector, varies with the menstrual cycle, peaks in early pregnancy and diminishes after menopause. This pattern suggests that the ability to taste bitter might be protective during pregnancy. However, the loss of the ability to taste bitter at menopause puts supertasting women at special risk for BMS. Dr. Bartoshuk’s findings led to specific recommendations for treatment, using an oral lozenge containing a substance known as capsaicin. This substance, which is commonly found in cayenne pepper, acts by desensitizing the pain receptors in the mouth that are responsible for BMS.

Determining If Menstrual Cycle Timing May be Key for Women Athletes' Surgical Recovery

Jeanette Ickovics, Ph.D.

Jeannette Ickovics, Ph.D., Associate Professor of Epidemiology and Public Health
(Collaborator: Marc Galloway, M.D.)

Laboratory studies suggest that pain threshold and immune responses vary according to the menstrual cycle. This study was designed to determine if surgical outcomes can be improved by correlating surgical procedures with the phase of the menstrual cycle. The study also was designed to examine post-surgery differences in social support and adherence to exercise regimens for men and women, both of which have been shown to influence the rate of recovery.

Highlighted Study Findings

Women are 4-5 times more likely to injure their knees severely during sports, for example by earing the anterior cruciate ligament (ACL) which provides stability to the knee, thus resulting in a greater rate of these surgical repairs in women than men. This study proposed to investigate gender differences in recovery trajectories following knee surgery, based on the rate and extent of rehabilitation throughout the six months after surgery. Due to a small sample, this investigation could not pursue the question of whether surgical outcomes could be improved by correlating surgical procedures with phases of the menstrual cycle. However, the investigators were able to gather preliminary data on social support and its relationship with recovery. There was a significant interaction between gender and perceived social support on two measures of pain at 6 months post-surgery; women who had lower perceived social support reported higher pain than women with higher perceived support, whereas men reported similar levels of pain regardless of their social support. Among ACL patients, men reported slightly higher knee function at 3 weeks and 6 months, although there were no gender differences on biomechanical function, or patients’ ratings of their pain. These findings bolster the importance of social support in surgical recovery and pain management.

Determining Optimal Therapy to Control GI Bleeding

Deborah Proctor, M.D., Associate Professor of Internal Medicine

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder, more common in women than men and characterized by abnormal vascular bleeding in different organs - particularly the gastrointestinal (GI) tract, which results in the need for multiple blood transfusions for many years. In this pilot study, Dr. Proctor aimed to determine how the use of oral estrogen-progesterone hormone therapy could reduce bleeding and subsequent need for blood transfusions based on anecdotal clinical data suggesting hormonal therapy may act to induce wound healing.

Highlighted Study Findings

Dr. Proctor conducted this study to evaluate the use of combination estrogen/progesterone hormone therapy to control GI tract bleeding with HHT. At the time this study was proposed, YNHH was a referral center for this disorder, however immediately after funding, this pattern changed preventing Dr. Proctor from enrolling multiple subjects as planned. Nonetheless, Dr. Proctor studied and published the data on a case study demonstrating promise for this therapy in a 51-year-old woman with HHT who had severe anemia and GI bleeding. The patient entered the study and received Ovcon 50, a high-dose combination hormone pill. Over the course of four months, the woman’s transfusion requirements decreased markedly. As a result of treatment, she no longer needed blood transfusions. Although this was a single patient, the case demonstrated that hormone therapy may be successful in some patients with HHT and GI bleeding.

Finding Out How Estrogen Affects Body Fluid Regulation

Nina S. Stachenfeld, Ph.D.

Nina S. Stachenfeld, Ph.D., Assistant Professor of Epidemiology and Public Health

Improper body fluid balance can lead to debilitating illnesses (including certain cardiovascular diseases), surgical complications, and problems with body temperature regulation. Vulnerability to these diseases, complications and conditions increases dramatically in women, as does changes in body fluid regulation, when radical shifts in sex hormones occur with menopause. This suggests that female sex hormones play a role in the interaction of body fluid regulation and disease vulnerability. Dr. Stachenfeld examined the actions of estrogen and progesterone on the systems that regulate body fluid balance.  This study was directed at understanding body fluid regulation as it relates to prevention and/or treatment of acute conditions and chronic diseases affecting women.

Highlighted Study Findings

This study was designed to characterize the actions of estrogen and progesterone on the systems that regulate body fluid balance and affect disease vulnerability. Because estrogen and progesterone have opposing effects on water regulation, and increase concurrently, albeit cyclically, in women of reproductive age, it has been difficult to study the individual actions of these hormones. In this investigation, the natural production of estrogen and progesterone in young women was prevented using an agent that suppresses ovarian function. Each hormone was then added back either as estrogen alone or estrogen plus progesterone to determine how these hormones alter body fluid distribution. The findings support a role for estrogen in the maintenance of body fluids by adjusting vascular functioning. The findings further indicate that high plasma progesterone levels reverse the protective effects of estrogen on plasma volume. Understanding the role of estrogen and progesterone on body fluid regulation is necessary in strategies for decreasing surgical complications due to fluid imbalance. In addition to improving our understanding of the role of sex hormones on body fluid regulation, this study demonstrated the influence of fluid dynamics on responses to temperature challenges and facilitated in the development of new strategies to help women avoid heat exhaustion or heat stroke.

Understanding Gender Differences in Brain that Affect Smoking Behaviors

Julie K. Staley, Ph.D.

Julie K. Staley, Ph.D., Associate Professor of Psychiatry and Diagnostic Radiology

Smoking is the leading preventable cause of death and disease in women, yet women find it more difficult than men to quit smoking, as evidenced by the lower quit rates for women seen annually since assessment began in the mid-1960s. Although not fully understood, the evidence that exists on the nature of cigarette smoking in women appears to show that the neurochemical basis of cigarette smoking differs between men and women, suggesting that gender-specific treatments are needed to assist women in their efforts to quit. In addition, emerging evidence suggests that the effects of nicotine vary across different phases of the menstrual cycle in women. Dr. Staley employed brain-imaging technology to investigate gender differences in nicotine receptors in the brain, and whether possible alteration in nicotine receptors across the menstrual cycle potentially could affect the efficacy of nicotine replacement therapies for women attempting to quit smoking.

Highlighted Study Findings

In previous work, Dr. Staley made the important discovery that women have higher nicotinic acetylcholine receptor availability than men. This new Ethel F. Donaghue Women’s Health Investigator Program-funded study was directed toward identifying and understanding possible alterations in nicotine receptors across the menstrual cycle in order to inform development of cessation therapies, particularly nicotine replacement therapy, for women. In imaging women who were nonsmokers, the results did not suggest that nicotine receptor availability varied during the menstrual cycle. Thus, change in receptor availability did not appear to account for variable success in smoking cessation over the cycle. The study did not rule out the possibility that women smokers may have alterations in receptors across the menstrual cycle. Dr. Staley’s findings laid some of the early groundwork for research that continues in the area of smoking cessation and the menstrual cycle. Following the sad and untimely death of Dr. Staley, her post-doctoral student, Dr. Kelly Cosgrove, carried Dr. Staley’s work forward and has now shown that nicotinic acetylcholine receptor availability is affected by sex hormones and is correlated with cigarette craving in women smokers. These findings are being used to inform drug development.

Pilot Project Study was funded in 2006, Dr. Staley †

Comparing Calcium with an Anti-Depressant to Treat Pre-Menstrual Dysphoric Disorder

Kimberly Ann Yonkers, M.D.

Kimberly Ann Yonkers, M.D., Associate Profssor of Psychiatry

Premenstrual Dysphoric Disorder (PMDD), which is characterized by emotional and physical symptoms, affects women’s relationships and interests, and can cause functional impairment within home and work environments. Dr. Yonkers compared an antidepressant (Sarafem® or Prozac®) commonly used in treating PMDD to calcium based on clinical observations and trials suggesting that calcium may work well in PMDD. Calcium had never been directly compared to an antidepressant used for PMDD. If its efficacy were confirmed, the more benign side-effect profile of calcium, in addition to the lower cost of calcium compared to an anti-depressant, would provide positive benefit to the many women who need and receive treatment for PMDD. In addition, her study was designed to determine if the addition of calcium to the antidepressant enhanced treatment response.

Highlighted Study Findings

Dr. Yonkers recruited and randomized 49 women subjects diagnosed with PMDD to either the antidepressant agent or calcium. The study was extended and expanded with a no cost extension in order to recruit the sample necessary. Preliminary data analysis shows there is little support for the efficacy of calcium as a treatment for PMDD, although results confirmed efficacy for fluoxetine. Moreover, calcium augmentation does not appear to be an effective strategy for enhancing the antidepressant treatment response.