Women With PMDD Respond to Stress And Pain Differently Due To Depression

 A severe mood disorder, premenstrual dysphoric disorder (PMDD), affects 5 percent to 7 percent of all women of reproductive age in the United States, but it is often misdiagnosed as major depression or other mood disorder.

A recent study further establishes that PMDD is biologically different from premenstrual symptoms, and that women with PMDD who have experienced depression could make up a subset.

The findings are important because they give physicians more reason to search for a more specific diagnosis and could possibly lead to more precise treatments, of which there are currently few good choices, said Susan Girdler, Ph.D., professor of psychiatry at the University of North Carolina at Chapel Hill School of Medicine who led the study.

“PMDD is not garden-variety premenstrual symptoms. PMDD causes severe impairment in quality of life, equivalent to post-traumatic stress disorder, major depressive disorder and panic disorder, that continually cycles on a monthly basis. Some women spend half their lives suffering from this disorder,” said Girdler, who also is director of the Stress and Health Research Program in UNC’s Center for Women’s Mood Disorders.

In a study published in the journal Biological Psychology, Girdler and her colleagues measured biological responses to stress and pain.

Previous studies demonstrated that women with chronic major depression have a heightened biological response to stress and release more stress hormones, such as cortisol. And, Girdler and her group have previously shown that women with PMDD respond conversely, with blunted stress responses.

The current study is the first known head-to-head comparison of the two groups and confirmed earlier findings.

“We found the greatest weight of evidence that PMDD and major depression are really two distinct entities in terms of biological response to stress and with respect to pain sensitivity and pain mechanisms,” Girdler said.

But more important, Girdler said, was the finding that women with PMDD who also had experienced depression in the past looked different from PMDD women who had never been depressed. Only the PMDD women with prior depression had lower cortisol and greater sensitivity to pain compared to non-PMDD women with prior depression. These differences between PMDD and non-PMDD women were not seen in women who had no depression history.

“So while the study shows that PMDD is biologically different from major depression, a history of depression may have special relevance for women with PMDD with respect to stress hormones and pain response,” Girdler said.

Current treatments for PMDD are effective in only about half of women. But, Girdler says, gathering more biological clues about PMDD could expand the treatment options.

Girdler and her colleagues are currently enrolling women with PMDD who would receive free diagnostic and medical tests, and who may be eligible for treatment studies and studies providing monetary compensation. Interested participants should call the UNC Center for Women’s Mood Disorders at 919-966-2547.

UNC recently expanded the Center for Women’s Mood Disorders to Rex Healthcare in Raleigh, where women can be seen for both a clinical evaluation and can be enrolled in research studies.

For more information, visit: www.med.unc.edu.

New Administration Could More Effectively Alleviate Menstrual Cramp Pain

While most women experience minor pain during menstruation, for others, the pain can be severe enough to interfere with everyday activities and require medication.

New research to be presented at the 2009 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition will reveal initial findings of safety surrounding a new device that may more effectively treat menstrual pain.

“The goal of our study was to find a better way to treat menstrual cramps,” said Giovanni M. Pauletti, Ph.D., associate professor at the University of Cincinnati and the study’s presenter as well as past chair of AAPS’ National Biotechnology Conference Planning Committee.

“Existing oral medications cause significant gastrointestinal side effects for women, creating additional discomfort while alleviating menstrual pain. Results from our Phase I clinical trials show that this new vaginal device safely delivers at least 10-times more drug to the uterus as a tablet of equivalent dose,” he said.

The study, which was sponsored by UMD, Inc., a Cincinnati drug delivery company, and conducted at Women’s Health Research, Inc. involved 18 study participants, aged 18-45 years with menstrual cycles between 25-30 days. During the mid-follicular phase of the first menstrual cycle (days 7-11), nine study participants received an oral dose of 10 mg of ketorolac (Toradol), a non-steroidal anti-inflammatory medication; while nine women received a tampon coated with 10 mg of ketorolac.

During the second menstrual cycle, each subject received the opposite treatment. The results of the study demonstrated that the medication administered vaginally does not cause significant side effects but accumulates more efficiently in the desired uterine tissue than using the oral medication.

“While still early in our research, this study shows promising results which may help pave the way for new treatment options for women,” said Pauletti. “Phase II clinical trials will study efficacy of the treatment to assess whether the drug concentration is effective in reducing pain.”

For more information, visit: www.aapspharmaceutica.com.

Women With Endometriosis Are At Risk For Preterm Birth

At the 25th annual conference of the European Society of Human Reproduction and Embryology a recent study revealed endometriosis to be a risk factor for premature birth in pregnant women.

Dr. Henrik Falconer, of the Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden, said that his team had found that women with endometriosis also had a higher risk of other pregnancy complications, as well as being more likely to give birth through Caesarean section.

The researchers investigated the association between adverse pregnancy outcome, assisted reproduction technology (ART), and a previous diagnosis of endometriosis in 1,442,675 single births to Swedish women. They found 13 090 births among 8922 women diagnosed with endometriosis.

Compared with women without endometriosis, they had a 1.33 greater risk of preterm birth. Women with endometriosis were also more likely to have difficulty in conceiving and need to receive ART, which is itself a risk factor for adverse pregnancy outcome.

Among women with endometriosis, 11.9% conceived after ART compared with the 1.4% of women without endometriosis who used the technique. The risk of preterm birth associated with endometriosis among women with ART was 1.24, and among women without ART 1.37.

“Endometriosis appears to be a risk factor for preterm birth, irrespective of ART,” said Falconer. “Our findings indicate that women with endometriosis may be considered a high risk group and have special care during pregnancy.”

Endometriosis is a chronic inflammatory disease, affecting up to 15 percent of all women of reproductive age, in which the endometrial cells that line the uterus are deposited in other areas.

Such displacement of endometrial cells can lead to anatomical distortion and also the release of anti-inflammatory cytokines, signaling molecules used in communication between cells. Symptoms of endometriosis include severe pelvic pain, heavy menstrual periods, and nausea.

In addition to an increased risk of preterm birth, the researchers also found other differences in the pregnancies of women with endometriosis. “Nearly twice as many women in this group were delivered by Caesarean section,” said Falconer.

“We observed that among these women the risk of induced preterm birth was higher than for spontaneous preterm birth. We believe that women with endometriosis are more frequently scheduled for preterm Caesarean section, possibly due to placental complications,” he said.

Women with endometriosis were also more likely to suffer from pre-eclampsia, a condition that develops in the second or third trimester of pregnancy and involves the development of high blood pressure and the presence of protein in the urine. Antepartal bleeding was also found to be more common among women with endometriosis, the researchers said.

“Because endometriosis is so strongly associated with infertility,” said Falconer, “we were not surprised to find that women suffering from it were of higher maternal age and had fewer children. However, after adjusting for maternal age and other confounding factors, the strong association between endometriosis and risky pregnancies still remained.

“Our research provides clinicians with important information in the search for the factors associated with premature birth. Given that endometriosis is relatively common in women of childbearing age, we hope that our results will lead to pregnant women with this condition receiving extra attention, thus enabling them to have normal pregnancies and give birth to healthy babies,” he concluded.

This research was published in Human Reproduction, for more information: www.eshre.com.

Bleeding Disorders Going Undiagnosed, New Guidelines To Help

Nearly one percent of the population suffers from bleeding disorders, yet many women don’t know they have one because doctors aren’t looking for the condition, according to researchers at Duke University Medical Center.

An international consortium specifically outlined the definitive signs that may signal the presence of a bleeding disorder in women, in hopes to diagnose more bleeding disorders.

The new guidelines aren’t just for doctors. Women who suffer from heavy menstrual cycles should be on the lookout for these signs as well, said Dr. Andra James, a Duke obstetrician, who says about 25 percent of women with heavy menstruation may have an undiagnosed bleeding disorder.

“Heavy bleeding should not be ignored,” said James, the paper’s lead author. “When a woman’s blood can’t clot normally the most obvious sign is a heavy period.” Yet when faced with these scenarios, most doctors aren’t suspecting a blood clotting problem is to blame.

“Sometimes they think hormones are the cause, or fibroids,” said James. “In some cases they recommend removal of the uterus or offer another gynecologic explanation when the real contributing factor is a blood clotting disorder.”

In previous studies, women who ultimately were treated for a bleeding disorder reported waiting 16 years, on average, before being diagnosed.

In extreme cases, James said undiagnosed bleeding disorders have led to women bleeding to death during menstruation, childbirth and surgical procedures.

The most common inherited bleeding disorder is von Willebrand disease, said James, author of 100 Questions and Answers About von Willebrand Disease.  Common criteria for diagnosis include the presence of a family history of bleeding, personal history of bleeding and laboratory tests that indicate the lack of a protein called von Willebrand factor which is essential for clotting.

Without the laboratory test, the consortium advised women and doctors should be on the lookout for the following:

• Heavy blood loss during menstruation
• Family history of bleeding disorder
• Notable bruising without injury
• Minor wound bleeding that lasts more than five minutes
• Prolonged or excessive bleeding following dental extraction
• Unexpected surgical bleeding
• Hemorrhaging that requires blood transfusion
• Postpartum hemorrhaging, especially if occurs more than 24 hours after delivery.

“Too often women think heavy bleeding is okay because the women in their family — who may also have an undiagnosed bleeding disorder — have heavy periods as well,” said James.

“We want women who continually experience abnormal reproductive tract bleeding, specifically heavy menstrual bleeding, to be alert to these other signs and approach their physicians about being evaluated.” In addition, she says doctors should be asking the right questions and ordering appropriate laboratory tests in suspected patients.

“Not every patient who has abnormal reproductive tract bleeding has a bleeding disorder, and most don’t,” James says. “But since up to one-quarter do, this needs to be recognized. Once treated, these women can expect to have normal periods and go through childbirth safely.”

The consortium’s meeting received financial support from CSL Behring and the consortium’s recommendations are published online and will appear in the July issue of the American Journal of Obstetrics and Gynecology.

More information can be found at, www.duke.edu.

Relapse Common Among Women Who Stop Taking Antidepressant Medication For PMS

About half of women whose symptoms of severe premenstrual syndrome are relieved by the antidepressant sertraline appear to experience relapse within 6-8 months after stopping medication, according to a new article. Women with more severe symptoms and those who took the drug for a shorter period of time may be more likely to relapse.

Premenstrual syndrome (PMS) is one of the most common health problems reported by women of reproductive age, according researchers at the University of Pennsylvania School of Medicine, Philadelphia. Several antidepressant medications, including sertraline hydrochloride, have been approved to treat the most severe form of PMS (known as premenstrual dysphoric disorder, or PMDD).

“There is little information about the optimal duration of treatment, although anecdotal reports and small pilot investigations suggest that premenstrual symptoms return rapidly in the absence of effective medication,” researchers said.

Dr. Ellen W. Freeman and colleagues at the University conducted an 18-month study involving 174 women with PMS or PMDD. Participants were randomly assigned to either a short-term or long-term treatment group; neither the women nor the researchers knew the treatment assignments. The 87 women assigned to short-term treatment took sertraline for four months and then were switched to placebo for 14 months, while the 87 assigned to long-term treatment took sertraline for 12 months and placebo for six months.

A total of 125 of the 174 patients (72 percent) showed improvement following treatment, most within the first four months. Relapse—defined as a return to the level of symptoms experienced before treatment—occurred in 41 percent of women after long-term treatment (median or midpoint time to relapse, eight months) and 60 percent of women after short-term treatment (median time to relapse, four months).

“Patients with severe symptoms at baseline were more likely to experience relapse compared with patients in the lower symptom severity group and were more likely to experience relapse with short-term treatment,” the authors wrote. “Duration of treatment did not affect relapse in patients in the lower symptom severity group.” The 41 patients (24 percent) who experienced remission, or a reduction of premenstrual symptoms to the normal post-menstrual level, after four months of treatment were least likely to experience relapse.

“How long medication should be continued after achieving a satisfactory response and the risk of relapse after discontinuing treatment are important concerns for women and clinicians, given the possible adverse effects and cost of drugs vs. the benefit of medication that improves symptoms, functioning and quality of life,” the researchers said. “These findings suggest that the severity of symptoms at baseline and symptom remission with treatment should be considered in determining the duration of treatment.”

This study was supported by a grant from the Institute of Child Health and Human Development, National Institutes of Health. Sertraline and placebo tablets were provided by Pfizer Inc.

For more information on the article “Time to Relapse After Short- or Long-term Treatment of Severe Premenstual Syndrome With Sertaline,” published in the Archives of General Psychiatry, visit: www.jamamedia.org

Enzyme May Be The Cause Of Endometriosis

Scientists at the University of Liverpool have identified an enzyme that could be responsible for endometriosis, a common cause of pelvic pain in women.

Endometriosis is patches of the inner lining of the womb appear in parts of the body other than the womb cavity. It can cause severe pain and affects approximately 15 percent of women of reproductive age. Endometriosis is also associated with infertility, with 50 percent of infertile women affected by the condition.

Researchers discovered that an enzyme, called telomerase, is released by cells in the inner lining of the womb during the latter stages of the menstrual cycle in women who are affected by endometriosis. Telomerase is not commonly found in the cells that make up the body, but is uniquely found in the inner lining of the womb and in some special cells, such as sperm and egg cells. The enzyme is also found in cancer cells and is thought to be responsible for replicating DNA sequences during cell division in chromosomes, said researchers.

Dr. Dharani Hapangama, from the University’s Department of Reproductive and Developmental Medicine, explained “Endometriosis occurs when cells of the inner lining of the womb are found growing outside of the uterus. At the time of a woman’s menstruation cycle these cells, called endometrial cells, are shed and can be expelled into the abdominal cavity. If these cells continue to live and are implanted in the pelvis and abdomen it can cause severe pain and in serious cases can lead to infertility.”

“We found the telomere – a region at the end of all chromosomes that prevents the chromosome destroying itself during cell division – is abnormally long in women with endometriosis. During menstruation telomeres normally shorten in length with each cycle of cell division until they reach a certain length at which they can no longer divide. An enzyme called telomerase can extend the length of the telomeres so that they can continue to divide and this can happen in some special cells such as sperm and egg cells, but not normally in cells that make up the organs of the body,” she said.

“Our research shows, however, that cells in the lining of the womb are unique in that they can express this enzyme in the early stages of the menstrual cycle when cell division is important, but not during the latter stages when implantation of the fertilized embryo becomes a priority,” she said.

“Women who have endometriosis express this enzyme in both the early and late stages of the menstrual cycle which means that the cells will continue to divide and lose their ‘focus’ in supporting the establishment of a pregnancy. As a result the lining of the womb may be more hostile to an early pregnancy, and the cells that are shed at this late stage in the menstrual cycle may be more ‘aggressive’ and more able to survive and implant outside the uterus, causing pain in the pelvic or abdomen area,” she concluded.

The study was published in the journal Human Reproduction; and more information can be found by visiting: www.liv.ac.uk.