T Cell Therapies Offer a New Way to Treat Gynecologic Cancers

Source: Memorial Sloan Kettering - On Cancer
Date: 09/30/2020
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The American Cancer Society estimates that more than 113,000 people in the United States are diagnosed with a gynecologic cancer every year. Memorial Sloan Kettering is a leader in treating people with these cancers, which include tumors of the cervixovaries, and uterus.

Among the new treatments being developed for gynecologic cancers are a type of immunotherapy called T cell therapies. These are treatments in which a patient’s own immune cells are modified to recognize and attack cancer cells. MSK doctors and scientists were the first to develop these treatments for leukemia and lymphoma. Now, many researchers are focused on further advancing this approach to make it effective against solid tumors.

“For certain blood cancers, cellular therapy can be remarkably potent, perhaps even curative,” says physician-scientist Christopher Klebanoff, whose lab is focused on developing new cell therapy approaches. One challenge of immunotherapy is directing the immune cells only to tumors so they don’t cause injury to healthy tissues.

Treating Cancer with CARs and TRUCKs

The most well-known cell therapy is chimeric antigen receptor (CAR) T therapy, which has shown success in treating certain blood cancers. CAR T modifies a patient’s immune cells (T cells) so they can recognize a protein (called an antigen) on the outer surface of cancerous cells. These supercharged T cells then seek out and destroy the cancer. For many cancers, especially cancers originating from a solid organ, the antigen isn’t quite as easy for the T cell to find, making cell therapies more challenging to develop.

This has led to a related tactic called T cell receptor (TCR) therapy, in which T cells are engineered to detect antigens on the inside of the cancer cell. “The ability to do this is one of the greatest tricks in biology,” Dr. Klebanoff says. “That is, how can you allow an immune cell to look inside other cells to detect if the proteins inside are normal or abnormal?”

As it turns out, the way this “looking” works is actually indirect: As part of normal cellular operations, proteins eventually get broken down and recycled to make new proteins. One step in this recycling process displays protein fragments on the surface of cells — allowing them to be seen by engineered T cells. TCR therapies are designed to take advantage of this natural process that the immune system uses to survey tissues in the body.

Some of the newest cell therapies known as TRUCKs — T cells redirected for antigen‐unrestricted cytokine‐initiated killing — work by combining the antitumor abilities of CAR T or TCR therapy with a molecule called a cytokine. The cytokine recruits another wave of immune cells to the tumor.

A Personalized Approach to Cancer Care

Medical oncologist Roisin O’Cearbhaill is the research director for the Gynecologic Medical Oncology Service and a leader in studying new cell therapies and immunotherapy approaches for treating gynecologic cancers, including a treatment for cervical cancer and other tumors caused by the human papillomavirus (HPV). “We’re building up our clinical trial program at MSK so that we will be able to offer more cellular therapies for patients with gynecologic cancers,” she says.

“With cell therapies, we use our knowledge about specific molecular and genomic properties of the patient’s cancer,” Dr. O’Cearbhaill explains. “And we may also use certain markers on their blood cells in order to get the best possible match for a targeted therapy for that individual patient.”

“For each of our patients, we take a very personalized approach to match the best possible medicines, including experimental medicines offered in clinical trials, with the patient’s disease,” Dr. Klebanoff says. “I’m a big believer in the concept of partnership and shared purpose, and this is how we work in collaboration with our patients. We have a shared purpose to try to improve things both for them and for others with similar diseases in the future.”

Clinical Trials Offering Cell Therapies for Gynecologic Cancers

MSK currently has a number of clinical trials that are examining this approach.

  • Dr. O’Cearbhaill is co-leading a phase I study with Dr. Klebanoff that is assessing the safety and effectiveness of using a TCR therapy called KITE-439 to treat cancers caused by a strain of HPV called HPV 16. The majority of cervical cancers as well as many cancers of the mouth, throat, vagina, vulva, penis, and anus are associated with HPV 16. In this study, a patients’ immune cells are modified to recognize and attack tumor cells that contain HPV 16.
  • The doctors are also co-leading a phase I trial for a cell therapy called KITE-718, which targets cancers containing MAGE-A3/A6, a protein found in some ovarian and cervical cancers as well as other kinds of cancer.
  • To study another treatment for ovarian cancer and cancers of the fallopian tubes and the peritoneal cavity (the lower abdomen), Dr. O’Cearbhaill is leading a phase I trial for a CAR T therapy that targets a protein called MUC16, which is made by many of these tumors. MUC16, also called CA125, is best known as a biomarker used to monitor treatment for ovarian cancer.
  • Dr. O’Cearbhaill is also leading a phase I/II trial for a TRUCK drug called TC-210, which is being tested in combination with chemotherapy. This cell therapy targets tumors that make a protein called mesothelin, which is found in several cancers, including some ovarian tumors.

Reality Check: Study Examines Metastasis after Breast Cancer Surgery

Source: Memorial Sloan Kettering - On Cancer
Date: 04/13/2018
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Earlier this week, scientists from the Massachusetts Institute of Technology published a study looking at some of the ways in which breast cancer spreads, or metastasizes, in mice. They reported data showing that surgery may trigger an immune response that makes it easier for cancer to spread throughout the body. Additionally, the study pointed to anti-inflammatory drugs like aspirin and ibuprofen as a possible way to decrease cancer’s ability to spread.

The news media reported on the research, which is still in early stages. These headlines may be scary or confusing for people facing a recent diagnosis, as well as for those who have already had surgery.

We spoke with Larry Norton, Memorial Sloan Kettering’s Senior Vice President and Medical Director of the Evelyn H. Lauder Breast Center, about what people should know about the study and why it shouldn’t affect decisions about treatment.

Can you tell us how this study was conducted?

This was a study done in the lab using a mouse model. The mice had been injected with cancer cells and then underwent simulated surgeries. Those mice later developed tumors. However, when the mice were given an anti-inflammatory drug at the time of the surgical procedure, the tumors were smaller.

I want to emphasize that this is an excellent lab experiment, and it fits in with much of the lab research we’re doing here at MSK. But it’s far from ready to influence clinical care.

What is the take-home message from the findings?

There is nothing in this study that should lead to any changes in the way we treat breast cancer. I don’t want anyone to read the media coverage of this study and think that they shouldn’t have surgery. That would be a disaster.

From studies conducted in London way back in the 1800s, we know that before doctors started doing surgery for breast cancer, everyone with breast cancer died. Some died soon after diagnosis, within months or a few years, and some lived for many years. But everyone eventually developed metastases and died from them. Surgery is still the mainstay of treatment for breast cancer and is the most important way to prevent metastases.

We have come a long way in the diagnosis and treatment of breast cancer since those early days, and today most people do very well. It’s true that some people still develop metastases, even if their cancer is caught early. Therefore, it’s clear that some tumors seed metastases very early in their development, long before they are ever detected and surgically removed. So it is not the surgery that causes the metastases.

What about taking anti-inflammatory drugs like aspirin or ibuprofen to reduce any potential risk?

I think a lot of people will hear about the study and grab onto this notion of taking these drugs at the time of surgery. But just because these drugs are available over the counter, it doesn’t mean they’re completely without risk. We know they can increase bleeding, and that may turn out to be more harmful than the response to inflammation.

It’s important to note that today many people with breast cancer get drug therapy before or immediately after their surgery. This includes chemotherapy and steroids. The steroids we give are much more potent than aspirin as far as their anti-inflammatory abilities. So there’s no reason to automatically assume that a small additional boost from aspirin or ibuprofen would make a difference. It’s an interesting question and it merits further research, but it’s something that needs to be studied with controlled clinical trials in patients.

What is MSK’s role in studying cancer metastasis?

MSK is conducting a great deal of research on the question of metastases. For example, Sloan Kettering Institute Director Joan Massagué is a world leader in studying how cancer metastasizes. Many of his studies also have looked the role of the immune system in suppressing cancer cells that have broken off from a tumor. He’s conducted research on how these cells later wake up and start to cause trouble. The biology is complex, and there are still a lot of things we don’t know. But everyone agrees this is a very important area of research, and one we will continue to study.

Is there anything else you’d like to say about the research?

This study was an interesting piece of well-conducted science. It’s certainly adding to our knowledge and giving us some ideas for new things to look at in the lab and in the clinic. But while it would be terrific if stopping metastasis were as easy as taking an over-the-counter anti-inflammatory drug, everyone studying metastasis knows that it’s not.

However, this work and much of the other work on this topic is pointing us in a good direction, with the ultimate aim of stopping cancer cells from spreading from the very beginning, or even before the beginning — as in cancer prevention. I do believe that the future is bright in this regard, although there is much work still to do to make it a reality.

What Women Should Know about Breast Density and Cancer Risk

Source: Memorial Sloan Kettering - On Cancer
Date: 10/26/2018
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In 2009, Connecticut was the first state to pass a law that requires radiologists to notify women who have had screening mammograms if they have dense breasts. Since then, more than 30 states have followed suit. Having dense breasts is a risk factor for breast cancer.

Breast density has to do with the amount of fibrous and glandular tissue that a woman has in her breasts compared with the amount of fat.

  • About 10% of women have extremely dense breasts.
  • Around 40% have heterogeneous density, which means their breasts are mostly dense with some areas of fat.
  • Another 40% have scattered density, which means they have some areas of density but most areas are not dense.
  • Only about 10% of women have breasts that are mostly fatty, with little or no fibrous and glandular tissue.

We spoke with Sandra Brennan, Director of Radiology at MSK Westchester, about what doctors know about breast density and what steps women with dense breasts can take to increase the likelihood that any cancer they may develop is detected early.

What does it mean when a woman is told that she has dense breasts?

Having dense breasts makes it more difficult for cancer to be picked up by a mammogram. The dense tissue looks white on the image, and that can obscure cancerous masses.

Women with dense breasts also have an elevated risk of breast cancer. The 10% who have the most dense tissue have a risk that’s four to six times higher compared with those whose breasts are the least dense. This is because glandular tissue is more likely to become cancerous. But even women with breasts that are mostly fatty can develop breast cancer.

What causes dense breasts?

Mostly it’s just part of the natural makeup of your body. Density is affected by age and hormones. Taking hormone replacement therapy will increase breast density, and conversely, taking tamoxifen (Nolvadex®), an estrogen-receptor drug used to treat some types of breast cancer, will decrease it. A woman’s breasts may become less dense as she ages. But that doesn’t always happen. Sometimes a woman with dense breasts can keep that density even as she gets older.

Is there anything women can do to reduce their breast density?

It’s not something you can really change. There are no foods or supplements that make a difference. Some women may have changes in the amount of fat in their breasts if they lose or gain weight. Women with a low body mass index tend to have dense breasts.

What are the screening recommendations for women with dense breasts?

We know that 3-D mammography, also known as tomosynthesis, is better at detecting masses in dense breasts than traditional 2-D mammography. This is because it looks at the breasts in visual slices and removes some of the masking effect of the overlying dense tissue. We offer 3-D mammograms as an option for standard screening to all women who get screened at MSK, both in Manhattan and at our regional sites.

Women with dense breasts should discuss with their doctor whether they should have supplemental screening with ultrasound. Screening breast ultrasound can pick up additional cancers that we might not see on a mammogram in women with dense breasts.

For women at a higher risk unrelated to their breast density, we recommend an annual screening with a breast MRI. This may detect small tumors that a mammogram misses. Women at a higher risk include those with inherited mutations in BRCA1 or BRCA2, a history of lobular carcinoma in situ, a previous biopsy that found atypical tissue, or a history of radiation to the chest wall at a young age. Breast MRIs are not routinely recommended for women with an average risk, including those with dense breasts, because the high number of false positives can lead to unnecessary biopsies.

Why are we hearing more about breast density now?

Radiologists have known about breast density since we began doing mammograms. It came to the public’s attention when breast density notification laws were passed. These laws came about largely because of patient activism.

What are some of the screening tests and other services that are available at MSK Westchester?

We offer 2-D and 3-D mammography, screening breast ultrasounds, and breast MRIs. Breast cancer screening services are available to MSK employees and their family members, MSK patients, and women in the community. Any woman who needs a screening mammogram can make an appointment to get one at MSK. We accept outside prescriptions for screening mammography and breast ultrasounds.

For those who need a breast biopsy, we perform a number of nonsurgical procedures at MSK Westchester. These include percutaneous ultrasound-guided core biopsies, fine-needle aspirations, stereotactic breast biopsies, and MRI-guided biopsies. People who are having surgery at Memorial Hospital in Manhattan can have their preoperative seed localizations and sentinel node injections done at MSK Westchester.

We are excited that we’ll soon be able to offer contrast-enhanced mammography at MSK Westchester. This technique, which gives us a vascular map of the breast, similar to an MRI, was first piloted at MSK’s Evelyn H. Lauder Breast Center in Manhattan. We are glad to expand that service to the regional sites, including MSK Westchester and MSK Commack. It’s a very specialized procedure that, to the best of my knowledge, is not available anywhere else in Westchester County.

For MSK’s Gynecologic Oncologists, Uncommon Cancers Aren’t Always Rare

Source: Memorial Sloan Kettering - On Cancer
Date: 09/27/2019
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In its annual listing of the country’s best hospitals, U.S. News & World Report ranked Memorial Sloan Kettering number one in gynecology for 2019. MSK’s oncologists, surgeons, nurses, and pathologists are the leaders in diagnosing and treating well-known gynecologic cancers, such as cervical cancerendometrial cancer, and ovarian cancer.

They also have vast experience in treating uncommon gynecologic cancers. This includes types that some healthcare providers may see only once or twice in their whole careers.

Here are some of the less common gynecologic cancers that MSK’s experts are successfully treating.

Vulvar and Vaginal Cancers

Vulvar cancer affects about 6,000 women per year, and vaginal and related cancers affect another 5,000. About 60% of these cancers are associated with human papillomavirus infections; these cases tend to develop in younger women. The other 40% are often caused by a skin condition called lichen sclerosus, which usually occurs after menopause.

MSK gynecologic surgeon Mario Leitao specializes in treating vulvar and vaginal cancers. These are usually squamous cell cancers similar to those that grow on other parts of the skin. Most women with these cancers have surgery as part of their treatment.

Dr. Leitao and his colleagues have conducted clinical trials on the use of sentinel node biopsies in these surgeries, including the use of new types of imaging agents to guide the procedure. Sentinel node biopsies involve removing only one or two lymph nodes in the groin area to test if the cancer has spread. This allows women to avoid side effects, like lymphedema of the legs, a debilitating and painful swelling that can occur when all the lymph nodes in that area are removed.

For those whose cancer comes back after treatment, MSK has additional options. “Our goal is to cure women when they first present with cancer,” Dr. Leitao says. “But when things don’t go the way we want, we’re a leading center for the larger, more complex surgeries that may be required.”

A rare subset of vaginal and vulvar cancers — about 1% — is melanoma. Dr. Leitao, medical oncologist Alexander Shoushtari, and radiation oncologist Marisa Kollmeier run a clinic for women with vulvar and vaginal melanoma. Patients are often able to see all three specialists on the same day.

As with other types of melanoma, immunotherapy with checkpoint inhibitor drugs is often used to treat gynecologic melanoma. The drugs may be given in combination with radiation therapy to improve their effectiveness.

“Each of these patients is unique, and we come up with a specialized treatment plan for each of them,” Dr. Leitao explains. “They all get their tumors tested with MSK-IMPACTTM, which can teach us a lot about the mutations driving these cancers. We are learning much more about the genetic and molecular makeup of gynecologic melanomas, with the goal of developing even better treatments in the future.”

Uterine Sarcoma

Most cancer of the uterus is endometrial cancer. This starts in the tissue that lines the uterus. Uterine sarcoma, which develops in the muscle or connective tissue, is much less common. There are several types of uterine sarcoma, including leiomyosarcoma, high-grade undifferentiated sarcoma, and endometrial stromal sarcoma. Uterine sarcoma is rare, making up less than 4% of all cancers of the uterus. Only 1,200 women are diagnosed with this disease in the United States each year.

Most uterine sarcoma is treated with surgery. Gynecologic oncologist Oliver Zivanovic specializes in these procedures. “The experience of the surgeon is very important,” he notes. “When these tumors are removed, achieving negative margins is very important. Some uterine sarcomas are quite large or infiltrate into the surrounding tissue, so it’s not always an easy surgery.”

For women who need chemotherapy after surgery, Dr. Zivanovic often collaborates with MSK medical oncologist Martee Hensley, an internationally recognized leader in treating these cancers.

One of the challenges of treating uterine sarcoma is that it often doesn’t have symptoms, or its symptoms are similar to much more common noncancerous conditions, like fibroids. Additionally, because it’s so rare, uterine sarcoma has no established screening methods. But experts at MSK have reported there is one group of women who are at a higher risk of leiomyosarcoma: those who have previously been treated for retinoblastoma, a type of eye cancer in children that is often hereditary.

For these women, Dr. Zivanovic and MSK ophthalmic oncologist Jasmine Francis have established a surveillance program, which offers annual exams with imaging including MRI and ultrasound. In addition to helping women at the highest risk of developing a second cancer, the investigators say that what they learn from these women will enable them to develop better detection strategies for all cases of uterine sarcoma.

Uncommon Ovarian Cancers

All ovarian cancers are considered rare, but some types are even less common. One of these, called small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), has had only about 500 documented cases to date. Despite its low incidence, MSK researchers have conducted extensive research on SCCOHT.

In 2014, MSK gynecologic surgeon Jennifer Mueller was part of a team that found a particular mutation in a gene called SMARCA4 present in this aggressive cancer. Although the discovery has not yet yielded any targeted therapies, further studies revealed that nearly half of these mutations are inherited. This discovery has important implications for family members of women diagnosed with these tumors.

Dr. Mueller recently performed risk-reducing surgery on a young woman who learned she had the SMARCA4 mutation after her sister was diagnosed with SCCOHT. The woman had her eggs retrieved and banked before the removal of her ovaries. “If it hadn’t been for the research done at MSK, as well as the genetic counseling offered to the family, this young woman would have never known she carried this risk,” Dr. Mueller says.

Dr. Mueller treats other less-common forms of ovarian cancer, including clear cell, endometrioid, and germ cell tumors. “For any woman who has one of these rare types, I would encourage her to get a second opinion with a pathologist who has experience in diagnosing them,” she says. “Getting a proper diagnosis can have a major impact on treatment decisions, which can, in turn, affect outcomes as well as a woman’s quality of life.”

Gestational Trophoblastic Disease

Gestational trophoblastic disease (GTD) is a tumor that develops from fetal tissue after a pregnancy, including a full-term delivery, a miscarriage, or an ectopic pregnancy. If the tumor is cancerous, it is called a gestational trophoblastic neoplasm (GTN).

These tumors are treated with surgery. More advanced cases may require chemotherapy. MSK medical oncologist Carol Aghajanian is a nationally recognized leader in treating GTN when chemotherapy is needed.

“The good news is that GTNs are almost 100% curable,” Dr. Mueller says. “But because they are uncommon, it’s important to make sure that you have the correct diagnosis. If a woman is diagnosed with a cancerous form and it turns out not to be cancer, she may be given additional treatments that she doesn’t need.”

Supportive Services

For women with gynecologic cancers of all types, MSK’s Female Sexual Medicine and Women’s Health Program, run by psychologist Jeanne Carter, offers comprehensive, personalized care.

MSK also has physical therapists who specialize in pelvic physical therapy. This process can be helpful in dealing with pelvic pain and pressure, which is especially common after radiation treatments.

Research Efforts Focus on Link Between Hormonal Contraceptives and HIV Infection

Source: Brigham and Women's - On a Mission
Date: 02/20/2019
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According to the World Health Organization, more than half of all married or in-union women of reproductive age use some form of contraception. Additionally, the number of women around the globe who either use contraception or have an unmet need for family planning is expected to grow by more than 900 million over the next decade.

One popular form of birth control is injectable hormonal contraceptives, predominantly the progestin-only form known as depot medroxyprogesterone acetate (DMPA, Depo-Provera®). Yet growing evidence has linked this form of contraception to an increased risk of HIV acquisition and transmission. Researchers at Brigham and Women’s Hospital are focused on determining the underlying causes for this connection and getting the word out about this important public health issue, which affects both women and men.

“This situation is particularly concerning because DMPA is the most commonly used contraceptive method in sub-Saharan Africa, the region that bears an estimated 70 percent of the global HIV infection burden,” said director of the Laboratory of Genital Tract Biology at Brigham and Women’s Hospital and Harvard University. “Our research provides a biologic explanation for the risks and variations in vulnerability to the potential adverse effects of hormonal contraception.”

Work coming out of Dr. Fichorova’s lab also has contributed to the understanding of inflammation and dysbiosis in women and newborns. Other research has looked at how bacteria, protozoan parasites and viruses act in concert to modify human host immunity. In 2018, Dr. Fichorova’s team received an Innovation Award from the Brigham Research Institute to translate their research and recently filed inventions into a novel live biotherapeutic for treatment of vaginal dysbiosis to prevent these conditions.

For the past five years, much of Dr. Fichorova’s research has focused on understanding how and why certain types of hormonal contraceptives change a woman’s biological defenses against infections—and HIV infection in particular. “If we can unveil the molecular pathways that lead to a predisposition to infection, we can discover novel drug targets for preventive medicine,” she said. “At the same time, we hope to lift a significant barrier to the rational design of new, safer contraceptive technologies.”

In one study, Dr. Fichorova and her colleagues analyzed cervical swabs and other data taken from more than 800 women enrolled in family planning clinics in Uganda and Zimbabwe. A major finding was that DMPA was associated with cervical immune imbalance and biomarkers of inflammation that were also associated with higher risk of HIV seroconversion in these women in the next three months.

The team also found higher shedding of HIV in those who seroconverted, thus suggesting pathways for both higher acquisition and transmission of the virus. They showed that DMPA had even broader immune-suppressive effects when acting on the background of abnormal vaginal microbiota characterized by lower abundance of lactobacilli and overgrowth of potentially pathogenic residential bacteria, a condition most often diagnosed as bacterial vaginosis. The data suggested that not only sexually transmitted infections such as herpes but also non-sexually transmitted reproductive tract infections and dysbiosis can make women more vulnerable to the side effects of DMPA.

To a lesser extent, changes in the cervical immune environment were also found in women taking a type of oral contraceptive where another synthetic progestin (levonorgestrel) was combined with synthetic estrogen.

Dr. Fichorova’s lab also has brought to the spotlight the fact that certain species of lactobacilli act as a sentinel of good health in the female reproductive tract, emphasizing the importance of treating conditions that are not sexually transmitted, such as bacterial vaginosis and yeast infections. Non-sexually transmitted vaginal bacteria prevalent in bacterial vaginosis can ascend to the uterus and cause placental epigenetic changes and systemic perinatal inflammation, leading to serious adverse reproductive and child health outcomes.

“Research enabling the design of safer contraceptive technologies is urgently needed. Women of reproductive age should not have to face impossible choices between preventing an unplanned pregnancy and preventing a devastating infection,” Dr. Fichorova concluded. “Understanding, properly diagnosing and treating non-sexually transmitted vaginal dysbiosis should be promoted as a powerful tool for prevention of contraceptives’ side effects as well as adverse pregnancy outcomes.”

Guidelines on Perimenopausal Depression Recognize Vulnerable Time in Women’s Lives

Source: Brigham and Women's Hospital - On a Mission
Date: 02/07/2019
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Perimenopausal mood changes and depression are experienced in some form by about one-fourth of women undergoing the transition to menopause. Yet until recently, there was no formal direction for healthcare providers in identifying and treating this condition. That changed in September 2018, when a panel led by the National Network of Depression Centers with the support of the North American Menopause Society published the first-ever guidelines.

“The three main hormonally linked mood conditions in women are postpartum depression (PPD), premenstrual syndrome (PMS) and perimenopausal depression,” said Hadine Joffe, MD, MSc, a psychiatrist and executive director of the Connors Center for Women’s Health and Gender Biology and vice chair of psychiatry research in the Department of Psychiatry at Brigham and Women’s Hospital. Dr. Joffe also served on the task force that developed the new guidelines. “PPD and PMS have been well-studied, but much less is known about perimenopausal depression than the other two,” she added. “Until now, there hasn’t been any guidance for clinicians in recognizing this as a vulnerable period in a woman’s life.”

Dr. Joffe explained that one reason for difficulty in identifying perimenopausal depression is that the period of risk usually stretches over several years and may not be immediately recognized, in comparison to a regular, cyclical event such as PMS or the distinct experience of giving birth. “Perimenopause is more nebulous,” said Dr. Joffe, who also is director of the Women’s Hormone and Aging Research Program. “Perimenopause lasts on average about four years. It’s hard to be able to pinpoint depression that arises during this time and say, ‘Aha, this is definitely hormonally linked.’”

Dr. Joffe’s research focuses on whether perimenopausal depression is a result of changes in reproductive hormones and/or common menopause symptoms such as hot flashes and insomnia. She also studies how to treat menopause-related symptoms, including the efficacy of hormonal and nonhormonal interventions for this constellation of symptoms. Last year, she co-authored the JAMA Psychiatry editorial, Should Hormone Therapy Be Used to Prevent Depressive Symptoms During the Menopause Transition?

The new guidelines for perimenopausal depression aim to help by providing information for healthcare providers. They focused on five main areas:

  • Epidemiology of depressive symptoms and depressive disorders
  • Clinical presentation of depression
  • Therapeutic effects of antidepressant medications
  • Effects of hormone therapy
  • Efficacy of other therapies, such as psychotherapy, exercise and natural health products

As members of the Brigham’s Women’s Mental Health Division, Dr. Joffe and colleagues focus on addressing the needs of women with depression and other mental health problems related to pregnancy, postpartum, PMS, perimenopause and other hormonal changes. These guidelines will be incorporated into their clinical practices and their teaching of medical students and psychiatry residents, many of whom are interested in women’s mental health and seek this expert knowledge for their future practices.

This Brigham team also trains others through a one-year dedicated Women’s Mental Health Fellowship. Working with Dr. Joffe, trainees are taught to recognize and treat perimenopausal depression. This training is part of a unique fellowship that provides highly expert and comprehensive training across the field of women’s mental health. Dr. Joffe also lectures on the topic at national meetings and local continuing medical education courses.

The most common symptoms of perimenopause are hot flashes and sleeping difficulties — not depression. But Dr. Joffe’s research has shown that women who experience the former issues are more susceptible to developing mild symptoms of depression, especially because lack of sleep can contribute to mood disorders.

Most women with mood changes during perimenopause have milder symptoms that do not constitute a full-blown mood disorder episode. However, a smaller group develops major depression during perimenopause. Those women generally have a history of depression, Dr. Joffe said. For these women, she added, it’s important to recognize perimenopause as a period of vulnerability for recurrence. Furthermore, physicians who treat these patients should monitor them more closely during perimenopause and should be careful about withdrawing treatment when women may be more vulnerable.

Dr. Joffe emphasized another important reason for creating guidelines: offering relief for those who are suffering. “The good news is that this condition is hugely treatable, once we recognize that it’s happening. It’s also important to recognize that this is a limited period of vulnerability and that the need for treatment passes once the woman passes through menopause and all the hormone changes settle down in postmenopause.”

For mild depression that is related to the hot flashes and sleep problems caused by hormone fluctuations, the task force noted that hormone therapy may be a beneficial approach for many women, particularly those with concomitant vasomotor symptoms, although estrogen therapy is not approved for this use. “If the depression is more severe or a recurrence of an earlier incident of depression,” Dr. Joffe concluded, “the best treatment is likely to be more traditional approaches, such as antidepressants and psychotherapy.”