Musings: Blog of the JAAPA Editorial Board

Musings

Blog of the JAAPA editorial board.

Monday, September 18, 2017

Elyse J. Watkins, DHSc, PA-C; Sheri Lim, DO

Fifteen years have passed since the preliminary results of the Women’s Health Initiative (WHI) upended the hormone replacement recommendations for menopausal symptom management. PAs in primary care and women’s health are at the forefront of recognizing and providing care for women with both vasomotor and vaginal complaints attributed to either natural or surgical menopause. Understanding the history and continued challenges with hormone replacement therapy is important.

In 1991, the National Institutes of Health (NIH) launched the landmark WHI to assess quality of life and major causes of death and disability in postmenopausal women.1 The study was designed to specifically address cardiovascular disease, osteoporosis, colorectal and breast cancer, and the role of hormone therapy in the prevention of these diseases. The three key components were a double-blind, placebo-controlled randomized controlled clinical trial, a community prevention study, and an observational study.

The clinical trial, which enrolled more than 68,000 women ages 50 to 79 years, had three arms: hormone therapy with conjugated equine estrogen and/or medroxyprogesterone acetate, dietary modifications, and calcium/vitamin D supplementation. Women had the option of enrolling in one or all three study arms.1

The community prevention study specifically addressed community-based healthful behavior modification strategies at 11 CDC-funded university-based prevention research centers across the country. It was designed to assess behavior change and disease prevention predominantly among black women.1

The observational study was offered to women who were ineligible for the clinical trial. This study included almost 94,000 women and sought to identify risk factors and biologic markers for disease. The study gave the researchers a population to compare with the clinical trial findings and let them further stratify the population by sociodemographics.1

The clinical trial
Women without a uterus were given either conjugated equine estrogen 0.625 mg every day or a placebo. Women with a uterus were given the same estrogen plus medroxyprogesterone acetate 2.5 mg every day or a placebo. In 2002, the NIH stopped the estrogen plus progestin arm of the study due to concerns about safety. Women taking conjugated equine estrogen and medroxyprogesterone acetate had an increased risk of myocardial events, cerebrovascular events, peripheral thrombotic events, breast cancer, and dementia. In early 2004, the NIH stopped the estrogen without progestin arm of the study due to safety concerns. Women taking conjugated equine estrogens had significantly higher rates of cerebrovascular events and peripheral thrombotic events. However, women taking estrogen had a decreased risk of fracture, but a negligible effect on colorectal or breast cancer.

The fallout
When the findings of the study were released to the public, many PAs and physicians were met with angry and confused patients. Many women abruptly stopped their hormone therapy. Some of us who were working in women’s health asked our office staff to identify all patients on hormone therapy and requested that they come in for an appointment to discuss stopping therapy. The pharmaceutical salespeople representing the estrogen used in the clinical trial were scrambling to maintain a sense of order and actively engaging in damage control. The effects of this pivotal moment in women’s health are still being felt by many prescribers and patients today with continued confusion of the treatment of menopausal symptoms and the role of hormone therapy.

Jewitt and colleagues quantified prescribing patterns after the WHI.2 They analyzed data regarding estrogen plus progestin use from the National Health and Nutrition Examination Survey and the National Prescription Audit 1970-2003. The authors found that estrogen and progestin use tripled in the 1980s compared with the 1970s. Hormone therapy use among women ages 45 to 64 years peaked in 1999 at almost 14%. However, after the WHI, use of hormone therapy in this age group declined to 2.7%. These statistics illustrate the effect of the WHI on hormone therapy prescribing practices across the United States.

Where are we now?
In 2016, deVilliers and colleagues summarized updated guidelines from a 2013 Global Consensus on Menopausal Hormone Therapy paper written by several international menopause and osteoporosis professional organizations.3 This new guideline summarizes the current state of the evidence and offers prescribers a concise guide to hormone therapy. It also allows providers to relay current, evidence-based information to their patients so that they can make informed decisions about whether to use hormone therapy.

Summary of the evidence
The consensus is that the benefits of estrogen therapy are likely to outweigh risks if estrogen therapy is initiated within 10 years of menopause or by age 60 years.4-6 However, the addition of a progestin to an estrogen regimen reveals a less robust benefit.3 A progestin is required in a women with an intact uterus if she is to take oral or transdermal estrogens to decrease the risk of endometrial hyperplasia. Data indicate that women who take estrogen and progestin in a combined hormone regimen have a statistically significant increased risk for breast cancer and thromboembolic events. Use of estrogen alone does not increase the overall risk for breast cancer, but the addition of medroxyprogesterone (the progestin used in the WHI), increases the overall risk, independent of age at initiation of hormone therapy. An increased risk for the development of cardiovascular disease in combined regimens was not statistically significant.7 Women with a lower baseline risk of cardiovascular disease also appear to benefit more from hormone therapy.5 Women who have risk factors for heart disease, thrombotic events, and breast cancer must be assessed individually with careful attention paid to modifiable risk factors and patient expectations.

Treatment strategies
Healthcare providers are advised to use the lowest dose to achieve maximal effectiveness in patients opting to use hormone therapy, and to use FDA-approved products that have undergone rigorous safety and efficacy testing. As such, individually compounded hormone regimens, including those that use micronized progesterone and/or estradiol, are not recommended due to concerns about potency, purity, and variability in bioavailability.4 The current recommendation based upon the most recent evidence about treatment duration is to use estrogen with progestin for no more than 5 years, and estrogen alone for no more than 10 years.3 Transdermal hormone therapy may offer a lower risk of thromboembolic events, including stroke.3 Women with symptomatic vulvovaginal atrophy with little or no vasomotor symptoms should be treated with nonhormonal lubricants first. If this therapy fails to ameliorate symptoms, patients should be offered treatment with topical vaginal estrogen.7 Available vaginal agents include creams, gels, rings, and pellets. Women with a uterus who use vaginal estrogens do not require progestin therapy. Systemic estrogen for women with vulvovaginal symptoms should only be considered if vasomotor symptoms occur as well.      

Overall quality of life, such as mood, sleep, and sexual function, may improve with hormone therapy. Estrogen may provide a benefit for early postmenopausal women experiencing depression and anxiety but antidepressant therapy is still first-line treatment for mood disorders.4-6 The antidepressants most often used are selective serotonin reuptake inhibitors and norepinephrine-serotonin reuptake inhibitors. In a study by Yaday and Volkar, gabapentin reduced menopausal hot flashes and nighttime awakenings.8

Menopausal hormone therapy is the only intervention that reduces post-menopausal hip and vertebral fractures, including in women with preexisting osteopenia. In women age 60 years and older, hormone therapy is considered second-line therapy for fracture prevention. Bisphosphonates are still first-line pharmacologic options for the prevention of osteoporotic fractures in postmenopausal women considered to be at high risk for a fracture per the National Osteoporosis Foundation guidelines.9

Cardioprotection may occur when estrogen alone is used within 10 years of menopause and among women younger than age 60 years. Data suggest that estrogen use in this population may decrease the risk of myocardial infarction and all-cause mortality but the US Preventive Services Task Force advises against using hormone therapy for cardiovascular disease prevention.3,6,10 Estrogen plus progestin in women within 10 years of menopause and younger than age 60 years reveals less compelling evidence of benefit.

Premature ovarian failure and surgical menopause
Women who undergo premature ovarian failure and surgical menopause before age 40 years have an increased risk of adverse cardiovascular events and osteoporosis.4-6 The addition of estrogen for these women has been shown to mitigate these risks. However, women with premature ovarian failure who still have a uterus will need treatment with a progestin in addition to estrogen to help prevent endometrial hyperplasia. Use of estrogen in women with premature ovarian failure has not shown an overall reduction in risk of dementia, but further studies may help elucidate this relationship. Hormone therapy for these women should be prescribed until about age 50 years, the average age of menopause. Longer duration of therapy requires individualized assessment not only of risks, but symptom severity. Patient preference and expectations must also be taken into account.

Alternatives for menopausal symptoms
Level A recommendations for prescription alternatives to hormone therapy include selective serotonin reuptake inhibitors and norepinephrine inhibitors, gabapentin, and ospemifene. Paroxetine is the only FDA-approved nonhormonal intervention indicated for relief of vasomotor symptoms. Ospemifene, an oral selective estrogen receptor modulator, is approved for postmenopausal moderate-to-severe dyspareunia but not vasomotor symptoms.4 In late 2016, the FDA approved the use of a dehydroepiandrosterone (DHEA) vaginal suppository for menopausal dyspareunia due to vaginal and/or vulvar atrophy.11

All women should be counseled with respect to achieving or maintaining a healthful weight, obtaining adequate exercise, stopping tobacco use, minimizing alcohol consumption, and preserving a positive quality of life. Some women may ask about complementary and alternative therapies, such as acupuncture and nutriceuticals, but there is no clear evidence to recommend for or against the use of these therapies.

Conclusion
Women younger than age 60 years who are within 10 years of menopause and are experiencing moderate to severe symptoms of menopause, such as hot flashes, may benefit from hormone therapy. Women desiring hormone therapy should use the lowest effective dose for the shortest duration of time to relieve symptoms. Women experiencing only vaginal symptoms should receive topical vaginal estrogen if lubricants fail to relieve symptoms.

Therapy should be individualized and consideration given to individual risk factors and expectations for quality of life. The route of administration and duration of treatment should align with the patient’s baseline risk assessment after a careful analysis of risk and benefit as well as patient preference. Lastly, hormone therapy should not be used solely for the prevention of chronic diseases, such as cardiovascular disease or osteoporosis.

REFERENCES

1. National Institutes of Health. Women’s health initiative.

2. Jewitt PI, Gangnon RE, Trentham-Dietz A, Sprague BL. Trends of postmenopausal estrogen plus progestin prevalence in the United States between 1970 and 2010. Obstet and Gynecol. 2014;124(4): 727-733.

3. de Villiers TJ, Hall JE, Pinkerton JV, et al. Revised global consensus statement on menopausal hormone therapy. Climacteric. 2016;19(4):313-315.      

4. American College of Obstetricians and Gynecologists. Practice Bulletin: Management of menopausal symptoms. Obstet Gynecol. 2014;123(1), 202-216.

5. Kaunitz AM, Manson JE. Management of menopausal symptoms. Obstet Gynecol. 2015;126(4): 859-876.

6. Moyer VA. US Preventive Services Task Force. Menopausal hormone therapy for the primary prevention of chronic conditions: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158:47-54.

7. Boardman LA. What is new in hormonal management and menopause? Best articles from the past year. Obstet Gynecol. 2014;123(3):661-663.

8. Yaday M, Volkar J. Potential role of gabapentin and extended-release gabapentin in the management of menopausal hot flashes. Int J Gen Med. 2013;6:657-664.      

9. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014;25(10):2359-2381.

10. Nabel EG. The Women's Health Initiative—a victory for women and their health. JAMA. 2013;310:1349-1250.

11. US Food and Drug Administration. FDA approves Intrarosa for postmenopausal women experiencing pain during sex.

Elyse J. Watkins and Sheri Lim are assistant professors at High Point (N.C.) University. The views expressed in this blog post are those of the authors and may not reflect AAPA policies.


Tuesday, September 5, 2017

Ellen D. Mandel, DMH, MPA, MS, PA-C

An article in this month’s issue titled “Infertility: A primer for primary care providers” aids our diagnosis and management of a common issue, failure of reproduction. As I navigate this article, reviewing the important phases of the menstrual cycle and the diagnostics and treatment for the “her” of the equation, I am once again struck by the intricacies of conception and how one should not take it for granted. And, as we know, there are couples thwarting the march of procreation.

However, I am most struck (maybe a better word is dismayed) by the statistic that “18% to 27% of the men from infertile couples lacked any evaluation,” which translates into a large number of men possibly having undiagnosed male factor infertility. This gives me pause. If having a baby “together” is a goal, then a full diagnostic workup should be a requirement of treatment, not an option.

According to the IVF Worldwide website, men and women react differently to infertility. This is no surprise. Women are more open about infertility issues, desiring discussion with their partner, family, and friends. However, if the infertility is due to a male factor, it is held in secret, as the woman seeks outside counseling, alone. This places quite a burden on the woman. The website relates that if male factor infertility is diagnosed, “some men can feel that they are less of a man.” Their masculinity is under siege, leading to both feelings of, and actual physical impotency. The website does not state that if female factor infertility is diagnosed, that the woman may feel like less of a woman.

If we allow an incomplete workup of infertility, we become part of the problem, not a solution. If a male factor is isolated, then the man needs emotional support along with the woman. A descriptive phenomenological study looked at 10 infertile men, isolating several themes. These include new somatic complaints (anorexia, chronic headache, insomnia), new-onset loss of libido and impotency, and the wife’s disinterest in sex with her infertile husband. However, these are the downsides. This study also reported that male factor infertility brought some couples closer.

Although modern science affords singles and couples reproductive options, the “classic” male and female coital approach prevails (for now). Somehow, sperm and egg must meet each other, in a laboratory or the fallopian tube. As PAs, we should cover all our bases when working up infertility, providing medical and psychological support. This includes the holders of both the XX and XY chromosomes.


Ellen D. Mandel is a clinical professor in the Department of PA Studies at Pace University-Lenox Hill Hospital in New York City. The views expressed in this blog post are those of the author and may not reflect AAPA policies.


Monday, August 21, 2017

Amy M. Klingler, MS, PA-C

This summer, I have spent a lot of time thinking about blacking out. But rather than syncope or substance abuse, I have been thinking about the total eclipse of the sun. On August 21, in many communities across the country, including mine, the moon will cross in front of the sun. Stanley, Idaho, is almost exactly in the center of the path of totality, where duration of darkness will last the greatest amount of time. For 2 minutes and 13 seconds, starting at 11:28:18 a.m., the skies will go dark, stars will twinkle, the temperature will drop, and crickets will (allegedly) start chirping. As a result of this unique experience, my town of roughly 200 year-round residents is expected to swell to 20,000 people on the days surrounding the eclipse. Normally, visitors to our area are a self-selected group of recreationalists who are used to hiking, biking, boating, climbing, and fishing. During the eclipse week, however, we are expecting tourists of all nationalities, ages, and fitness levels to descend on our area to bear witness to this astronomical phenomenon.

While I have been wondering where all of these people will poop, pee, and dispose of their trash, I have been planning for how to provide their medical care. I have recruited additional paid and volunteer staff, expanded clinic hours, and created an incident management plan for our emergency services. Based on my research and consulting with other clinicians who have experienced a total or partial eclipse, I am preparing to treat the standard urgent care medical issues along with increased numbers of patients with dehydration, sunburns, musculoskeletal injuries, intoxication, the consequences of on- and off-road motor vehicle crashes, and the inevitable retinal burn.

Altitude illness often is a concern for people visiting Stanley, which is situated at an elevation of 6,300 ft. Although I don’t think of it as extreme elevation, patients often become symptomatic after traveling here. I was thrilled to read the article Out of air: Is going to high altitude safe for your patient? in this month’s issue of JAAPA. The article provides a great review of the effects of altitude on underlying medical conditions, the risk of patients with certain medical conditions for developing altitude illness, and prevention and treatment of altitude illness. I hope at least some of the stargazers will take the recommended precautions before heading this way to stand in the shadow of the moon.

Amy M. Klingler practices at the Salmon River Clinic in Stanley, Idaho. The views expressed in this blog post are those of the author and may not reflect AAPA policies.
 


Monday, August 7, 2017

Zachary Hartsell, MHA, PA-C, DFAAPA

As a PA who has worked internationally, I was drawn to the special article by Kerlen and Ballweg in the August 2017 issue of JAAPA. Ando Kerlen is a Dutch-trained PA who has also worked in South Africa and Australia; Ruth Ballweg is an education leader who has promoted the PA profession internationally for decades. This combination of contributors provides both an interesting perspective as well as experience in developing the PA profession internationally and navigating different healthcare systems. Kerlen and Ballweg outline some of the similarities in the PA profession between these countries as well as the differences in their development based on culture and healthcare system needs. What was interesting is that two common themes emerged for PA development in other countries: provider maldistribution and patient accessissues that the United States also faces.

Another theme of the article that resonated with me was the give-and-take Kerlen described when practicing in another country. In both developing PA professions in South Africa and Australia, Kerlen relates that he not only contributed to the development of the profession but also learned significantly from the providers with whom he worked. This give-and-take is an element that I can relate to in my own international experience. I also feel that it is an important element in the success of advancing an international PA profession in the future. I believe that the future international success of the profession will rely on exchanges of ideas as opposed to applying a set model.

I worked in Scotland as part of a National Health Service research project studying the effect of PAs on different healthcare care environments throughout the country.1 I worked in an ED outside of Glasgow from the end of 2007 through 2008.2 From the start, my experience was much more than simply introducing the PA profession to the NHS. The experience was truly two-sided. In that year, I not only helped demonstrate the value of PAs but I was able to grow significantly as a provider while being introduced to new models of care delivery. Many of the things I learned in Scotland, I still use today.

Although the pilot project was found to be overall successful, I understand the PA profession in Scotland continues to develop slowly. Colleagues have told me that the profession is facing many of the political challenges described by Kerlen, and which PAs in other countries also face. Nevertheless, the PA profession in the United Kingdom continues to move forward and with continued support can be a source of unique insight into innovative care delivery models for PAs here in the United States (for example, innovations in population health and home-based care). Likewise, the Netherlands PA profession is well established and has produced interesting research on the use of PAs in inpatient units.3 Perhaps the development of the PA profession in South Africa and Australia can yield innovative models for using PAs in caring for rural or underserved populations. Both are problems that we struggle with today.

A robust international network is important to the PA profession. PAs in the United States, the country with the most established of the PA professions, should lead the way in developing this network. Examples of the type of support that could be beneficial would be greater recognition of international PA trends and successes, research into differences between PA deployment models, and advocacy support. In launching this type of support, we also should understand that this exchange should not be one-sided. The real benefit comes from our learning about the deployment of PAs and workforce models that have been proven to solve similar healthcare problems faced by other countries.

REFERENCES
1.  Farmer J, Currie M, Hyman J, et al. Evaluation of physician assistants in National Health Service Scotland. Scottish Medical J. 2011;56:130-134.

2. Hartsell Z, Kehoe K. A day in the life. JAAPA. 2008;21(8):20,22.

3. Timmermans MJ, van Vught AJ, Maassen IT, et al. Determinants of the sustained employment of physician assistants in hospitals: a qualitative study. BMJ Open. 2016;6(11):e011949.

Zachary Hartsell is program director and vice chair of operations and workforce development and an associate professor in the PA program at Wake Forest University in Winston-Salem, N.C. The views expressed in this blog post are those of the author and may not reflect AAPA policies.


Monday, July 24, 2017

Brian K. Yorkgitis, PA-C, DO

The growing opioid epidemic increases pressure on the healthcare community to tackle this issue. The rate of opioid-related deaths has increased over time. The CDC estimated more than 33,000 deaths in 2015% were attributed to opioids. Included in this number is deaths caused by prescription medications, which was estimated at close to 22,500 in 2015.1 In 2013, the NIH estimated 2 million people suffered from substance use disorder related to prescription opioid pain medications, with the number only expected to rise. Each day, 1,000 people are treated in EDs for inappropriate prescription opioid use.2

No one chooses to become part of this statistic; they have a disease. As clinicians, we must focus on how we can help patients through prevention and treatment. We must think carefully each time we prescribe an opioid. Every time I approach a patient in pain, I hope to get it RIGHTT…

Risk for adverse event—Look for patient risk factors for opioid abuse or misuse (use the opioid risk tool developed by Webster).3 Use your state’s prescription drug monitoring program if available.

Insight in to pain—Set functional goals for pain relief rather than a number. Most of the time, you can’t make patients pain-free so the goal is to keep them functional.

Going over pain plan—Discuss with your patient a stepwise approach to analgesia. Use nonopioids first, such as NSAIDs, acetaminophen, gabapentin, or pregabalin. If opioids are needed, use them in conjunction with nonopioid adjuncts to allow the minimal dose of opioid possible.

Halting opioids—Opioid duration should be as short as possible. Communicate with your patient the duration that you would expect a patient with that condition to require opioids. Advise them that longer durations are associated with increased risk of dependence.

Throwing away unused medications—Discuss methods to dispose of unused opioids to prevent diversion (local drop-off locations, mixing unused pills in kitchen waste or cat litter).

Trouble—If you feel your patient is developing trouble with opioids, offer assistance instead of chastising.

Be a PArtner in this growing problem through these simple steps. Invest the time in getting it RIGHTT; the return on your investment could be lifesaving.

REFERENCES
1. National Institutes of Health, National Institute on Drug Abuse. Overdose death rates. 

2. Centers for Disease Control and Prevention. Prescription opioid overdose data.

3. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Med. 2005;6(6):432-442.

Brian K. Yorkgitis practices in the Division of Acute Care Surgery at the University of Florida-Jacksonville. The views expressed in this blog post are those of the author and may not reflect AAPA policies.