ABNORMAL UTERINE BLEEDING
Our expert is Christine Isaacs, M.D., Associate Professor, Obstetrics and Gynecology, Virginia Commonwealth University. She is the Division Head of General Ob/Gyn and the Director of Midwifery Services. Her clinical specialties include Natural Childbirth, Laparoscopic and Abdominal Surgery, Women’s Reproductive Health, Contraceptive Management, and Peri- and Postmenopausal Health.
If there is a medical topic you would like to see explored here, please let me know!
WHAT IS NORMAL UTERINE BLEEDING?
To understand abnormal bleeding, we need to know what is normal. Most ovulatory menstrual cycles occur in intervals of 21-35 days, with the average duration of flow being 4-7 days. For two years after menarche, irregular menses are common and usually considered normal, but after that, the length of the menstrual cycle remains relatively constant throughout the reproductive years, and during this period in a woman’s life, blood loss should be relatively predictable and consistent.
CATEGORIZING ABNORMAL UTERINE BLEEDING IS IMPORTANT FOR TREATING IT
We need to use universal nomenclature for describing abnormal uterine bleeding (AUB). This is an important issue because one-third of all outpatient visits to the gynecologist are for AUB, and AUB accounts for more than 70% of all gynecologic consults in the perimenopausal and postmenopausal years.
Knowing the nomenclature is important to clinicians because being able to categorize the different causes of AUB helps with establishing the diagnosis and treatment of various conditions. It also provides an opportunity to collect data, promote research, and further advance women’s health globally.
THE PALM-COEIN CLASSIFICATION SYSTEM
The acronym PALM-COEIN helps the clinician create and think through the different diagnoses for AUB. The PALM part refers to structural causes, including Polyps, Adenomyosis, Leiomyomas, and Malignancies. The COEIN part of the acronym refers to nonstructural causes including Coagulopathy, Ovulatory dysfunction, Endometrial origins, Iatrogenic causes, and etiologies Not yet classified.
THE DESCRIPTIONS A PATIENT GIVES OF HER SYMPTOMS MAY NOT MATCH CLINICAL REALITY
If a patient is close to menarche or menopause, irregular menses can be expected. Otherwise, something to keep in mind is that when she’s describing “heavy” or “light” bleeding, she might not mean what you are thinking by these terms. Her frame of reference is subjective, and what she perceives as heavy bleeding may in fact be relatively normal and what she perceives as normal may be excessive. Since her subjective experience may not reflect the actual clinical severity of the situation, try to clarify and elaborate on the extent to which there’s a significant change in what she’s used to.
RULE OUT PREGNANCY
It’s important always to rule out pregnancy when making the diagnosis of AUB. It’s rare for a contraceptive device, when used correctly, to fail, but it can occasionally happen, even in the case when the contraception being used is a tubal ligation or long-active reversible contraception such as an implantable device or intrauterine device. Therefore, an appropriate first step may be a pregnancy test. As an example, if a 38-year-old woman with a normal menstrual history is suddenly having unexplained bleeding, the possibility of pregnancy is something to consider.
WHEN AN ENDOMETRIAL BIOPSY IS NEEDED
An endometrial biopsy should be performed when trying to rule out malignancy or premalignant endometrial cells. In general, this should be part of the work-up for a woman over age 45 with AUB. If she is less than 45 but there is a clinical suspicion that she is at risk for endometrial hyperplasia/cancer, such as in the case of morbid obesity or polycystic ovarian syndrome (PCOS), an endometrial biopsy may be warranted.
SYMPTOMS OF COAGULOPATHY
Some young women will present for the first time to an urgent care center, emergency room, or women’s health office with recurrent excessive menstrual bleeding noted since menarche. These women should have a medical history directed to screen for an underlying disorder of hemostasis. A history that also includes bleeding associated with dental work or surgery, and easy bruising, epistaxis, gum bleeding, or a family history of bleeding should prompt testing for coagulopathies such as von Willebrand’s Disease. A 16-year-old female who is found to be newly anemic and fatigued should raise some clinical suspicion for a coagulopathy. While she may describe her monthly menses as “normal” upon initial questioning, her frame of reference is limited and may understate a true pathology.
NEWS YOU CAN USE: RECENT STUDIES THAT MAY CHANGE YOUR PRACTICE
Our expert is Melissa McNeil, MD, MPH, Chief, Section of Women’s Health, Division of General Internal Medicine, University of Pittsburgh. She is affiliated with multiple hospitals in the area, including Magee-Women’s Hospital of UPMC and UPMC Presbyterian Shadyside. She received her medical degree from the University of Pittsburgh School of Medicine and has been in practice for 34 years.
Dr. McNeil was one of the most popular speakers at the Academy of Women’s Health April 2014 Conference in Washington with her talk on Recent Studies That Changed My Practice. This week’s blog post is a refresher, for those who were lucky enough to hear Dr. McNeil, and an introduction for those who didn’t. Her clinical pearls involve the latest research that she believes can change how people think about their practice today. If there’s a story relating to women’s health that you’d like to see explored here, just let me know!
ORAL ESTRADIOL CARRIES LESS RISK FOR CLOTS THAN CONJUGATED EQUINE ESTROGENS
New research shows considerable variation in the risk of venous thrombosis when using different forms of estrogen therapy. In a comparison of transdermal estrogen, oral estradiol and conjugated equine estrogens (CEE), the results were: transdermal estrogen posed the least risk of venous thrombosis; oral estradiol was in the middle of the risk category; and CEE posed the highest risk. All estrogen therapies carry an increased risk for venous thrombosis, but the conjugated equine estrogen carries a higher risk, and in addition, it may pose a higher risk of myocardial infarction. Providers should consider the differences in these risks when making decisions about which hormone therapy preparation to prescribe.
EXTEND USE OF TAMOXIFEN FROM 5 YEARS TO 10 YEARS
It has long been known that a five-year program of using adjuvant tamoxifen for treating estrogen receptor positive breast cancer reduces recurrence for the first decade and reduces mortality by a third through the first 15 years. However, new data suggest that women should consider continuing with tamoxifen for 10 years rather than stopping at 5 years. A randomized study of 12,894 women studied the effects on both mortality and recurrence for those who ended their treatment in 5 years and those who continued for 10 years. Women who continued their treatment for 10 years experienced a further reduction in recurrence and mortality. The take-home message is that longer hormone therapy for breast cancer is better.
RECOMMEND ULIPRISTAL FOR EMERGENCY CONTRACEPTION
Emergency contraception (EC) is designed to prevent ovulation that has not yet occurred. Since sperm can live for five days, the goal of EC is to prevent follicular rupture during those five days. The traditional emergency contraceptive that we have been using, levonorgestrel (LNG), may be no more effective than a placebo when used in the late follicular phase. Ulipristal, in contrast, can prevent follicular rupture for a full five days. Ulipristal is therefore the drug of choice for emergency contraception. It is effective in 75- 80% of cases. A disadvantage of ulipristal is that it is not currently available over the counter.
RADIOTHERAPY FOR BREAST CANCER INCREASES THE RISK OF LATER CVD
A prior history of ionizing radiation for breast cancer is a risk factor for ischemic heart disease and should be assessed when thinking about risk factors for coronary artery disease. The radiation may have been life-saving, but exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the risk of subsequent ischemic heart disease. The risk begins as early as 5 years after radiotherapy and substantially changes the risk assessment of women for CAD.
POPULATON-BASED ANNUAL MAMMOGRAPHY IN WOMEN AGED 40-59 DOES NOT REDUCE MORTALITY
Mammogram screening has yet to show mortality benefits for women who are under 60 and who have an average risk for breast cancer. While population-based screening doesn’t provide health benefits, there are also serious costs involved. Twenty-two percent of screenings result in false positives, which generate unnecessary additional tests and personal anxiety. Instead of population-based screenings, the timing of when to begin screening and the interval between screenings needs to be individualized according to the patient’s personal risk of breast cancer and her own choices. In the case of women who are at high risk for breast cancer, there are other interventions that have been established to decrease risk by up to 50%. Tamoxifen or raloxifene should be considered for targeted chemoprevention for women who are at high risk.
HIV PREVENTION IN A CLINICAL CARE SETTING
Our expert is Jeanne Marrazzo, MD, MP. She is a Professor in the Division of Allergy and Infectious Diseases in the Department of Medicine, University of Washington. Her research includes biomedical prevention of HIV. As the Medical Director of the Seattle STD/HIV Prevention Training Center, she is also involved in education for providers and students.
If there is a medical topic you would like to see explored here, please let me know!
BE ALERT TO THE POSSIBILITY OF ACUTE HIV INFECTION IN YOUR PATIENTS
Although the incidence of new HIV-1 infections has decreased by 1/3 in the years since 2001, there will nevertheless be approximately 2.3 million new cases worldwide this year. Of these, 50,000 will occur in the United States. Roughly 15,000 will be women.
EARLY DETECTION NEEDED TO SLOW THE EPIDEMIC
In the past decade, we have had extraordinary success with approaches to prevention. These include: prevention of mother-to-child HIV transmission; medical male circumcision; pre-exposure prophylaxis; vaginal microbicides; and prevention of transmission to uninfected partners of an HIV-infected person with the help of effective antiretroviral therapy. What’s needed now for slowing the epidemic further still is prevention and also early detection. This means more broadly based testing coupled with high levels of both treatment and adherence.
HIV PREVENTION IS A PART OF PRIMARY CARE FOR WOMEN
Some still think of HIV as a gay man’s disease, and tend to leave women out of the risk assessment and decision-making. This is unfortunate because women are vulnerable to HIV. Further, 16% of HIV positive individuals do not know they have it, and they account for a disproportionate number of new infections. We recommend that everyone have an HIV test at least once in their lifetime, and more often if they are at increased risk of acquiring HIV. Have a conversation about HIV with your patients and recommend that at some point they be tested.
INTEGRATE BEHAVIORAL RISK ASSESSMENT WITH TARGETED RISK REDUCTION
Individuals who are not infected with HIV but are at high risk should be receiving interventions. Is the woman dating a guy whose HIV status is unclear and she’s concerned? Or maybe she knows he is HIV positive but it’s under control with antiretroviral medications? Maybe her partner is HIV positive, she wants to become pregnant and is worried about delivering a healthy child? Has she recently been diagnosed with a sexually transmitted infection? Does she use injected drugs or share needles? In any of these cases, consider pre-exposure or post-exposure prophylaxis.
PROPHYLAXIS AND RISK REDUCTION
Many insurance plans will cover pre-exposure prophylaxis for women at high risk. We recommend daily emtricitabine/ tenofovir disoproxil fumarate for pre-exposure prophylaxis in the cases of those at high risk for HIV. For persons who inject drugs, harm reduction services should be provided, including needle and syringe exchange programs or supervised injection. They should also have access to medically assisted therapies, including opioid agonists and antagonists, and low-threshold detoxification and drug cessation programs. Post-exposure prophylaxis is recommended for all persons who have sustained a mucosal or parenteral exposure to HIV from a known infected source, and this should be initiated as soon as possible.
CONTRACEPTION FOR WOMEN LIVING WITH HIV OR WITH A PARTNER WITH HIV
If a woman is concerned about becoming infected with HIV, counsel her to use condoms. If she is HIV-positive, hormonal contraception does not increase the risk of complications of HIV and should be offered as needed.
MANAGING URINARY TRACT INFECTIONS
Our expert is Thomas M. Hooton, MD, Associate Chief of Staff, Miami Veterans Healthcare System and Professor of Clinical Medicine at the University of Miami Miller School of Medicine. His specialty is infectious diseases.
If there is a medical topic you would like to see explored here, please let me know!
URINARY TRACT INFECTIONS (UTIs) ARE COMMON
UTI is the most common bacterial infection encountered in the ambulatory care setting in the United States. By age 32, half of all women report having had at least one UTI, and among young, healthy women with cystitis, the infection will recur in 25% of them within six months. The recurrence rate increases when there’s more than one prior UTI.
BACTERIAL CULTURE USUALLY NOT NEEDED FOR UNCOMPLICATED UTI
We define an uncomplicated UTI as one involving a healthy, ambulatory, non-pregnant woman with no history of genitourinary, anatomic, or functional abnormalities. UTIs in everyone else are considered complicated. In the case of an uncomplicated UTI, there is such a high correlation between the typical UTI symptoms and laboratory confirmation of infection that a bacterial culture is usually not needed. If you do perform a urine culture in these cases, you may be wasting two or three days waiting for the results and meanwhile, your patient is suffering. Our recommendation for women with typical UTI symptoms is: treat her immediately with antibiotics, and have her call you if she doesn’t get better. An exception to this is if she’s sexually active and has a history of STDs, you might want to culture for chlamydia. If your patient is hospitalized or in a nursing home or using a catheter or has symptoms or signs of kidney infection (e.g., fever), or is otherwise thought to have a complicated UTI, we recommend, across the board, having a culture taken.
E. coli causes 90% of UTIs, and in women the voided urine culture is highly predictive of bladder infection when it comes to finding E. coli bladder infections. On the other hand, there’s a risk that the lab culture will give a false negative for E. coli, given that most laboratories do not routinely report colony counts less than 104 CFU/ml. Such laboratories will miss as many as 20- 30% of symptomatic UTIs. Further complicating interpretation, enterococci and group B streptococci in voided urine may represent urethral contamination rather than bladder infection. If a woman is not symptomatic, even when bacteria are found in the culture, it is not necessary to treat.
AIM TO REDUCE ANTIMICROBIAL USE
There is an increase in antimicrobial resistance worldwide. As just one example, between the years 2000 and 2010, the Surveillance Network reports that urinary E. coli resistance for ciprofloxacin increased from 3% to 17%. In this regard, antibiotic resistance prevalence varies by uropathogen, but for commonly used oral drugs it may be as low as 5% for nitrofurantoin to >50% for amoxicillin. Because resistance complicates treatment, we need to practice antimicrobial stewardship. In cases where the UTI symptoms are mild, the infection may clear on its own. Randomized trials using placebos show that most patients tend to get better over time and that the body’s own immune system can take care of most infections. In the case of a very mild UTI, a reasonable strategy for handling it, if your patient is agreeable to this approach, is to increase fluids, take a urinary analgesic, and delay antibiotics for a couple of days and see if the UTI clears on its own. In cases where antibiotic therapy is needed, choose a short course treatment. There are no first-line recommended regimens that would last seven days.
STRATEGIES TO REDUCE RISK OF UTI RECURRENCE
In older women, topical vaginal estrogens have been helpful. Cranberry is a widely used OTC product, but there is conflicting evidence as to whether or not it is effective in decreasing UTI risk. Another OTC product, D-mannose, a natural sugar, inhibits the attachment of E. coli to urinary mucosa, which means that the bacteria can be flushed out when voiding. We don’t have a lot of data on D-mannose yet, but absence of data doesn’t mean it doesn’t work. Fortunately, both cranberry and D-mannose can be obtained without a prescription. Another strategy is avoiding using either a diaphragm or a spermicide-coated condom for birth control (if another method can be used), since both of these have been shown to increase the risk of UTI. There are also behavioral changes that may be effective, such as drinking more water and not delaying going to the bathroom to urinate. Of course sexual intercourse is the strongest risk factor for UTI, so reducing its frequency, if feasible, should be effective in reducing the risk of UTI.
INVITE YOUR PATIENT WITH RECURRING UTI TO KEEP A DIARY
There are several strategies that haven’t been tested, but they may work for your individual patient. Ask her to see what in her daily routine seems to correlate with recurrent UTI. As noted above, if cranberry or D-mannose seem to work, then by all means encourage their use. See if increasing the amount of fluids consumed daily makes a difference. Some have suggested an association with tight-fitting underwear versus looser cotton underwear, and shower versus tubs baths. If the patient thinks something they have tried works, then encourage its use as long as it seems safe. Antibiotics are highly effective but should be discouraged until antibiotic-sparing approaches have been tried and used only in patients with frequent recurrences of bothersome symptomatic UTIs.
Menopause and Cardiovascular Disease
Our expert is Virginia M. Miller, PhD, Professor of Physiology and Surgery at the Mayo Clinic, where she is Principal Investigator of a Specialized Center for Research of Sex Differences and Research Director for Building Interdisciplinary Research Careers in Women’s Health. Dr. Miller’s work includes studying how estrogen affects progression of atherosclerosis and changes in brain structure and cognition at menopause. If there is a medical topic that you would like to see explored here, please let me know.
MENOPAUSE HAS AN IMPACT ON CARDIOVASCULAR DISEASE
Menopause is associated with dramatic changes in the sex steroid estrogen, and these changes can accelerate the development of cardiovascular disease. Women lag behind men in developing cardiovascular disease until menopause and then the risk for developing cardiovascular disease increases to become about the same as for men.
ESTROGEN TREATMENTS ARE NOT ALL THE SAME
There are benefits and harms associated with the use of estrogen treatment for menopausal symptoms and one of the major issues that needs to be addressed, both by scientists and clinicians, is the tendency to lump all estrogen treatments together. The Women’s Health Initiative, which showed adverse cardiovascular consequences for hormone replacement therapy, used conjugated equine estrogen (CEE) for women without a uterus and, in women with a uterus, the estrogen was used with a synthetic progestogen. However, other estrogen preparations, such as oral estradiol and transdermal estrogen, have different and more favorable risk profiles.
ONE SIZE DOES NOT FIT ALL
It is important to keep in mind the age and underlying health conditions of the women who are using these products. Data from observational and epidemiological studies and the Women’s Health Initiative show that attention needs to be given to the health status of women when prescribing hormone replacement therapy. Those who are at low risk for a cardiovascular disease may do well with hormone replacement therapy, in contrast to those who have higher cardiovascular risk factors.
HRT NEEDED FOR PREMATURE OR SURGICALLY INDUCED MENOPAUSE
Another very strong case of one size not fitting all is women who have either had premature menopause or a surgically induced menopause. After the Women’s Health Initiative study, it seemed as if hormone replacement therapy was bad for everyone, but in these two cases, the benefits clearly outweigh the harm. Depriving these women of HRT increases the risk of mortality. Women in these two categories benefit if they receive HRT until natural menopause would have occurred.
CLINICIANS NEED TO REQUEST ADDITIONAL STUDIES
The cardiovascular system of women differs greatly from that of men, primarily because of the need to adjust to pregnancy. This leads to the assumption that treatment results will not be the same for women as for men. Although there have been some published studies on the differences in response to different treatments, more women are needed in clinical trials, and clinical trial data analysis needs to be done by sex. To develop the guidelines for what treatments are effective for women, more data are needed to provide useful information for clinicians to use in their practices. We need a groundswell of clinicians asking for these kinds of studies.