Hello current and future volunteers! What better way to celebrate spring than by reading this issue of “Participating in NIH Research.” It is focused on women's health issues and offers useful information about participating in NIH clinical studies.

The Central Nervous System Effects of Pharmacologically Induced Hypogonadotropic Hypogonadism with and without Estrogen and Progesterone Replacement
Study Number: 92-M-0174
The purpose of this study is to evaluate the effect of the hormones progesterone and estrogen on women's mood, behavior, and mental functioning.

This study will evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in healthy volunteer women without PMS.

Participants will undergo the following tests and procedures: A physical examination including blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.

5HT1A and SERT Imaging During Pharmacologically Induced Hypogonadotropic Hypogonadism With and Without Estrogen and Progesterone Replacement
Study Number: 05-M-0059
This study will explore possible hormonal causes of menstrual-related mood disorders (MRMD) by stopping the menstrual cycle with a drug called Lupron and then giving in sequence two menstrual cycle hormones, progesterone and estrogen. The study will first evaluate Lupron's effectiveness in treating MRMD and will then examine the effects of giving estrogen and progesterone on mood and behavior. In addition, positron emission tomography (PET) and magnetic resonance imaging (MRI) will be used to study serotonin receptors and transporters – molecules in the brain that are thought to play a major role in mood changes related to the menstrual cycle. Menstruating women between 18 and 45 years of age who are in good health, not pregnant, and not taking medications may be eligible for this study.

Participants undergo the following tests and procedures: Physical examination, blood draw, and Lupron drug treatment. A total of six PET scans are done at three different times during hormone treatment and MRI scans.

An Endocrine Model For Postpartum Mood Disorders
Study Number: 95-M-0097
The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. This protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms.

This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters as well as response to o-CRH (a separate protocol done in collaboration with NICHD).

FSH-Stimulated Inhibin B as a Marker for Early Ovarian Insufficiency
Study Number: 00-CH-0189
The purpose of this study is to gain information about normal ovarian function that will be useful in developing a test for early detection of ovarian failure. The ovaries produce female hormones, such as estrogen, that are important in maintaining a woman's health. When the ovaries do not work properly, problems can develop. Unfortunately, there is no test that can detect ovarian failure early in its course. By the time premature ovarian failure is diagnosed in young women, two-thirds have already developed osteopenia (loss of some bone mass) and nearly one in ten have osteoporosis, (greater loss of bone mineral density that weakens bones and increases the risk of fractures). Women with normal ovarian function ages 18 to 25 may be eligible for this study.

Participants will undergo the following tests and procedures: Full medical history, physical examination, blood tests, hormone injections, and vaginal ultrasound examination.

More Clinical Trials

• Individuals 18 and older needed for an MRI / Imaging study.
• Tongue movement study for individuals 21–80 years
• Tongue movement study for individuals 60–80 years
• Healthy Children needed for Mood and Anxiety Disorder study

Search for more examples of clincal trials for healthy volunteers at http://clinicalstudies.info.nih.gov/. Please type the word “Healthy” for a full listing of Healthy Volunteer opportunities.

	Dr. Peter J. Schmidt joined the NIMH after completing his medical internship and psychiatry residency at the University of Toronto, Canada. His laboratory is interested in the neurobehavioral effects of gonadal steroids in humans, including the roles of  gonadal steroids in mood-state regulation in women with menstrual-related mood disorders, perimenopause-related depression and puerperal depression. Q: How long have you been working with healthy volunteers in your studies? A: Basically, since day one. We've relied on the contributions of our healthy volunteers since Dave Rubinow founded the program in 1981. Q: What other doctors do you work with? A: There are several physicians who either work in our group or with us in collaboration including Pedro Martinez, Khursheed Khine, Lynnette Neiman, and Karen Berman. Q: Is your focus primarily adult or pediatric? A: Mostly adults. Q: How many healthy volunteers do you usually work with every year? A: Around fifty. Q: Why are healthy volunteers so important for your research? A: Healthy volunteers help us to determine the way the brain functions under normal or “disease-free” conditions. We are able to use this information to compare with the measurements in our patients to figure out how hormones affect the brains of women with mood problems. Q: What is your motto regarding your research? A: Everybody on my team shares the same spirit and dedication. We all believe that we are indebted to the people who volunteer for our studies and we feel that it is a privilege to work with the volunteers. If it weren't for volunteers, our research wouldn’t be possible. Because of the volunteerism of both our patients and our normal volunteers, we’ve been able to run one of the longest standing women's health studies at the NIH.

National Institute of Mental Health Studies the Role of Hormones in Postpartum Depression Each year postpartum depression (PPD), a common and serious condition, affects millions of women worldwide, occurring in approximately 10% of women after childbirth. Symptoms include sadness, anxiety, trouble sleeping, tearfulness, hopelessness, fear of hurting the baby, an inability to enjoy anything and rarely, in its most severe form, psychosis. Despite the prevalence of this condition, there have been relatively few studies examining the potential causes and treatment of PPD. Early studies focused largely on the role of psychosocial events surrounding pregnancy and delivery. More recent studies have suggested a role for hormones in precipitating depression. Following delivery, the levels of both estrogen and progesterone drop dramatically, and some researchers believe that the precipitous change in these hormones may be responsible for depression in a subgroup of women. However, there is no evidence that women with PPD have abnormal levels of hormones produced either during or after pregnancy, so how could the hormones be involved in PPD? One possible answer was provided in a study by Bloch, et. al. who demonstrated that women with a history of PPD are more sensitive to the changes in the levels of estrogen and progesterone than are women without a history of PPD. Therefore, the hormone levels are not abnormal, but the response to them is. What is it that makes some women vulnerable to depression in relation to these hormonal changes related to childbirth? If changes in hormone levels after delivery contribute to PPD, would supplementing these hormones during the postpartum period help relieve the depression? The answers to both of these questions currently remain unanswered, however, there is evidence that postpartum depression may have a genetic component, particularly in its most severe form (postpartum psychosis). Identifying genes that might contribute to a vulnerability to developing PPD might be helpful, not only in identifying women at risk but potentially for targeting effective treatments for this disorder. Surprisingly few treatment studies of PPD exist, but preliminary evidence suggests that estrogen supplementation may treat or guard against the development of postpartum depression.