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Trends in Pharmacy Compounding
for Women’s Health in North Carolina:
Focus on Vulvodynia
Susan H. Corbett, PharmD, Gary Cuddeback, PhD, MPH, Jasmine Lewis, BS,
Swasan As-Sanie, MD, and Denniz Zolnoun, MD, MPH
Objectives: To identify trends in compounding pharmacies with a
focus on women’s health and, more specifically, the types and combi-
nations of medications used in the treatment of vulvodynia.
Methods: This survey study was conducted with 653 nonchain
pharmacies that compound medications. Each pharmacy was asked
to complete a 19-item online survey assessing general practice and
common compounding indications, focusing on women’s health.
Results: Of the 653 pharmacies contacted, 200 (31%) responded to our
survey. Women’s health issues ranked third (19%) among the common
indications for compounding, preceded by otolaryngology (30%) and
dermatology (28%). Of the medications compounded for women’s
health, the most common indication was bioidentical hormone therapy
(73%) followed closely by vaginal dryness (70%)and low libido (65%).
Vulvodynia, or vulvar pain, was the fourth most common indica-
tion for compounding medication for women’s health issues (29%).
Vulvovaginal infections were reported as an indication for compounding
medications by 16% of respondents.
Conclusions: Vulvovaginal symptoms are a common indication for
compounding medications in women’s health. Further research in
understanding the rationale for using compounded medications, even
when standard treatments are available for some of these symptoms
(eg, vaginal dryness, vulvovaginal infections), is warranted.
Key Words: compounding pharmacy, vulvodynia, vulvovaginal
infections
Compounding pharmacies have come under much scru-
tiny following the fungal meningitis outbreak caused
by preservative-free methylprednisolone linked to the New
England Compounding Center in Framingham, Massachusetts.
1
As of February 4, 2013, the Centers for Disease Control and
Prevention reported 696 cases of fungal meningitis across 20
states, resulting in 45 deaths (the initial outbreak occurred in
2012).
2
As a result of this tragedy, the Verifying Authority and
Legality in Drug Compounding Act was introduced in Congress
in November 2012.
1
The purpose of this act is to give the US
Food and Drug Administration the necessary authority to
oversee compounding pharmacy practices across the country.
1
Unfortunately, the 2012Y2013 outbreak is not the only inci-
dence of patient harm caused by compounded preparations during
Key Points
&Compounding pharmacies are important for patients who
have medical conditions such as vulvodynia that have few, if
any, commercially available treatments.
&Congressional efforts to tighten regulations on com-
pounding pharmacies, although necessary, will undoubtedly
affect health care, with a potentially profound impact on
women’s health issues.
&For better patient outcomes from medications prescribed to a
compounding pharmacy, we believe proper communication
between the doctor and pharmacist and the pharmacist and
patient is essential to ensure medications are compounded in
the most effective manner as possible.
Original Article
Southern Medical Journal &Volume 107, Number 7, July 2014 433
From the UNC Pelvic Pain Research Center, Divisionof Advanced Laparoscopy
and Pelvic Pain, Department of Obstetrics and Gynecology, University of
North Carolina School of Medicine, Chapel Hill, the School of Social Work,
and the Cecil G. Sheps Center for Health Services Research, University of
North Carolina, Chapel Hill, the Department of Obstetrics and Gynecology
and Centerfor Neurosensory Disorders, University of NorthCarolina, Chapel
Hill, and the Department of Obstetrics and Gynecology, Division of Mini-
mally Invasive Gynecologic Surgery, University of Michigan, Ann Arbor.
Reprint requests to Dr Denniz Zolnoun, Department of Obstetrics and Gyne-
cology, University of North Carolina School of Medicine, Chapel Hill, NC
27599Y7570. Email: denniz_zolnoun@med.unc.edu
This research was supported in part by the National Vulvodynia Association,
National Institute of Health award K23 HD 053631, UL1RR025747 from
the National Center for Research Resources, and the Department of
Obstetrics and Gynecology at the University Of North Carolina School of
Medicine and at the University of North Carolina at Chapel Hill.
The authors have no financial relationships to disclose and no conflicts of
interest to report.
Accepted February 4, 2014.
Copyright *2014 by The Southern Medical Association
0038-4348/0Y2000/107-433
DOI: 10.14423/SMJ.0000000000000138
Copyright © 2014 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
the last decade nor was the 2012 compounding act the only leg-
islation proposed to implement stricter regulation of compounding
pharmacy practices. In 2007, the Safe Drug Compounding Act
wasintroducedinanattempttoprovidetheFoodandDrugAd-
ministration with tighter regulatory control over compound-
ing pharmacies and the medications compounded.
3
Although
in some respects necessary, tighter governance of compounding
pharmacy practices has the potential to adversely affect ad-
vances in novel therapeutics and compromise patient care.
4
One patient-specific population likely to be negatively or
positively affected by the aforementioned legislation is women
with vulvovaginal conditions such as vulvodynia. With limited
commercially available therapies, patients and clinicians alike
routinely refer to compounding pharmacies for treatment op-
tions. Despite a population prevalence of approximately 15%,
vulvodynia remains an elusive disorder characterized by
chronic vulvar burning, stinging, rawness, soreness, or pain in
the absence of objective clinical or laboratory explanations.
5
Vulvodynia and related pain disorders may be considered a
‘‘pseudo-orphan disease,’’ which is a condition that is ‘‘not
adopted by the pharmaceutical industry because it provides little
financial incentive for the private sector to make and market new
medications to treat or prevent it.’’
6
Alternatively, according to
US criteria, a rare disease, one that affects fewer than 200,000
people, can be given orphan status. Clearly, vulvodynia is not a
rare condition because it affects approximately 1 in 10 women
at some point in life. In addition, it is not feasible to obtain
pharmaceutical investment in research and development because
the condition is deemed etiologically heterogeneous with con-
siderable controversy on nomenclature and treatment.
7
Vulvodynia has received increasing attention by both the
medical profession and media, and more women are aggres-
sively seeking care.
5
No standard treatment exists, however,
leaving many women and their treating physicians to rely on
compounded medications and word of mouth to control the
symptoms of this complex condition. The extent to which the
compounded formula is based on rational pharmacological
principles with potential or definite benefit (eg, Bendectin,
combination of doxylamine succinate and pyridoxine hydro-
chloride, for treatment of nausea during pregnancy
8
) versus an
expensive and potentially ineffective venture for the desperate
or misinformed patient is unknown. Our hypothesis was that
compounding for women’s health constitutes a significant portion
of compounding pharmacies’ practice. Focusing on vulvodynia,
we further sought to characterize common indications and
specific formulations dispensed by compounding pharmacies.
Methods
We identified all registered pharmacies (n = 2304) across
North Carolina by contacting the North Carolina Board of Phar-
macy. After excluding chain pharmacies (44%, n = 1020), we
attempted to ascertain whether the remaining nonchain pharma-
cies (56%, n = 1284) compounded medications for human use.
After three attempts at contacting nonchain pharmacies, we were
unable to determine the compounding status for 127 pharmacies
(10%), 114 pharmacies could not be reached, and 13 pharmacies
refused to participate. Of the remaining 1157 nonchain phar-
macies contacted, 504 (44%) pharmacies indicated that they
did not compound medications for human use; therefore, our
cohort consisted of 653 (56%) registered pharmacies in North
Carolina that compounded medications for human use (Fig.).
We administered a 19-item online questionnaire to assess
demographics, practice patterns, common compounding indi-
cations, and types of medications compounded. This 19-item
questionnaire, focusing on compounding practices surround-
ing women’s health and, more specifically, vulvodynia, was de-
veloped in consultation with the survey methodology team
at the University of North Carolina Social Sciences Research
Center (Odum Institute).
We did not offer an incentive for participating in this study;
however, to increase the response rate, we sent e-mail or postal
reminders, depending on a respective pharmacy’s preference.
Up to three reminders were mailed 8 to 10 weeks apart during
the study period. With each reminder, individual pharmacies
were provided with their unique four-digit identification code
along with detailed instructions on accessing the online survey.
Skip patterns were used in the survey. For example, if
the pharmacists entered 0 for the percentage of compounded
medications dispensed on average per day for human, adult, or
women’s health, they were directed to the end of the survey. This
Fig. Disposition of responders.
Corbett et al &Trends in Pharmacy Compounding for Women_s Health
434 *2014 Southern Medical Association
Copyright © 2014 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
strategy was used to limit responses from pharmacies that did
not meet the qualifications for study participation.
Results
The daily prescription volume for commercially avail-
able medications was normally distributed in our cohort. The
200 pharmacies that responded to our survey represented an
unskewed geographic distribution across the state of North
Carolina. Of the 200 respondents, 75 pharmacies filled 101 to
200 (38%) prescriptions per day. Forty-five pharmacies (22%)
and 35 pharmacies (18%) dispensed 201 to 300 and G100 pre-
scriptions per day, respectively. Thirty-four pharmacies (17%)
indicated prescription volumes of 9300 prescriptions per day.
Data were missing for 11 pharmacies (5%).
The majority of pharmacies (79%, n = 149) compounded
medications for both adults and children and 21% (n = 40)
compounded for adults only. Of the 195 pharmacies reporting
the number of prescriptions compounded per day, the majority
(90%, n = 175) filled G25 compounded prescriptions per day;
7% (n = 14) reported compounding between 26 and 50 pre-
scriptions per day, whereas only 3% (n = 6) reported com-
pounding 951 medications on average per day.
Three common reasons for compounding medications
were combination of medications not commercially available
(44%, n = 86), drug not commercially available (24%, n = 46),
and dosage form not commercially available (22%, n = 43).
Furthermore, reflecting on the 30 days preceding the survey,
the most common indications for compounding medica-
tions represented as an average percent were otolaryngological
applications (eg, magic mouthwash, nasal irrigations) (30%),
dermatological preparations excluding vulvovaginal prepa-
rations (28%), and women’s health issues (eg, vulvovaginal
pain, vaginal infection, vaginal dryness, sexual dysfunction,
bioidentical hormone therapy) (19%).
Eighty-six of the pharmacies surveyed reported dispensing
compounded medications for women’s health issues. Among
the 86 pharmacies, 73% (n = 63) reported compounding for
bioidentical hormone therapy, 70% (n = 60) for vaginal dryness,
65% (n = 56) for low libido, 29% (n = 25) for vulvar pain, 27%
(n = 23) for other health issues, and 16% (n = 14) for vulvovaginal
infections. (Respondents could report compounding for multiple
indications, thus allowing the percent sum to exceed 100%.)
Among the 25 respondents who reported compounding
medications for vulvar pain during the previous 30 days, most
(92%, n = 23) reported that of the total number of prescriptions
compounded for women’s health, G25% were for the indication of
vulvar pain. The top five frequently occurring medications used
at least once during the preceding 12 months in compounding
preparations for vulvar pain were lidocaine (60%, n = 15), es-
tradiol (52%, n = 13), estriol (52%, n = 13), testosterone
(52%, n = 13), and progesterone (44%, n = 11). Respondents
also were queried on the different strengths of estradiol they
used in compounded preparations for vulvar pain in the pre-
ceding 12 months. Among the 13 respondents who reported
compounding with estradiol, the strength most often used
was 0.01% (85%, n = 11), followed by 0.02% (54%, n = 7),
0.025% and 0.03% (both at 31%, n = 4).
The most common combination of medications com-
pounded for vulvar pain was estradiol, lidocaine, and testosterone;
however, there was considerable variation in the combinations
used. On average two, but as many as four medications, were
compounded in preparations for vulvar pain. In addition, the
two most common bases used in compounded preparations for
vulvar pain were emollient cream (40%, n = 10) and petrolatum
(36%, n = 9).
Compared with pharmacies that reported having no phar-
macists with special training in compounding medications (65%,
n = 130), pharmacies reporting having at least one or more
pharmacistswith special training (35%, n = 70), on average, filled
a greater percentage of prescriptions for compounded medica-
tions specifically for women’s health issues in the 30 days pre-
ceding the survey (5% vs 41%, respectively), and this difference
was statistically significant (t(91) = j9, PG0.001). When asked
about the specific categories of medications compounded within
the previous 30 days, the 70 pharmacies reporting one or more
pharmacists with special training in compounding medications
reported the following four reasons for compounding: women’s
health issues (41%), dermatological conditions (18%), otolar-
yngological conditions (14%), and pain management (9%).
Discussion
Compounding pharmacies play a pivotal role in meeting
the unique needs of patients and providers. In many situations,
patients and providers turn to compounding pharmacies as a
last resort to treat medical conditions. In some conditions,
compounded medications are simply a different formulation (eg,
suppository vs oral suspension) of an already-effective therapy
with well-characterized pharmacokinetics and dosing. In other
instances, however, compounded medications serve as the final
effort in treating conditions with no known standard of treat-
ment; alleviating vulvovaginal complaints often falls into this
category.
Legislative attempts to tighten governmental control of
compounding pharmacies without a contextual assessment of
the role of compounding pharmacies in patient care will not be
sufficient to meet the intended objective of quality assurance
in dispensing practices. Scientific merit aside, women view
compounded formulations as ‘‘safe, with fewer side effects and
are equally or more effective for symptom management.’’
9
Development of guidelines and standards in dispensing prac-
tices will serve to ensure the safety in patient care and prac-
titioners, and although such a practice has long been endorsed
and implemented in some areas of compounding practices, no
such recommendations have been established in compounding
formulations in women’s health.
10
Although a study targeted independent community phar-
macies in Illinois, Missouri, Kansas, and Iowa,
11
to our knowl-
edge ours is the first statewide survey in North Carolina to focus
Original Article
Southern Medical Journal &Volume 107, Number 7, July 2014 435
Copyright © 2014 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
on compounding practices with a special focus on women’s
health, specifically vulvodynia. One limitation of our study that
should be noted was the poor response rate of 30%, likely
meaning that our respondents are not universally representative.
We believe that the respondent pharmacies are more conscien-
tious, thus representing the ‘‘cream of the crop’’ of compounding
pharmacies. We are unable to comment about the direction of
bias in our results; however, our findings were consistent with the
study’s clinical observation. Nevertheless, it is curious that a high
percentage of compounded medications were for the indications
of hormonal therapy and vaginal dryness, areas in which there
are a number of commercially available alternatives.
Another interesting result was the most common base used
to compound medications for vulvar pain, emollient cream.
When referring to the vulvar region, a wet mucosal surface, a
sticky base (eg, hydrophilic petrolatum) would be the best
delivery vehicle; therefore, use of emollient cream could lead
to decreased absorption of medications and ultimately decreased
efficacy. The obvious question is why would compounding
pharmacies use a suboptimal base? On the surface the answer
seems simpleVlack of communication among physicians,
pharmacists, and patients; however, in reality, this lack of
communication is an immense and complex problem that is
compromising patient care.
10
Often when physicians write pre-
scriptions, they do not include a medical indication on the pre-
scription. In many situations, the pharmacist does not ask the
patient details about the prescription before compounding, and
therefore the pharmacist compounds the medication in the most
common base.
To address these deficiencies, practice standards for
compounding preparations such as those that exist for the
standard preparation for total parenteral nutrition are necessary.
Based on our experience in this study, we believe that such
standards should include but not be limited to the medication
indication, area of application (mucosal surface vs nonmucosal
surface), doctor-to-pharmacist communication to ensure com-
plete understanding of medication usage, and pharmacist-to-
patient communication before compounding the medication to
ensure that the medication is compounded in the most effective
manner as possible for the individual patient. Matheny and
Martin discussed the vital role that compounding pharmacies
play in providing medications not commercially available, and
included questions that patients should ask their compounding
pharmacist regarding the compounding facility and quality of
medication.
12
We want to conduct a follow-up survey focused on
vulvodynia, but narrow our compounding pharmacy participants.
Specifically, we want to focus on those compounding phar-
macies that meet both criteria of only compound medications
(ie, do not dispense commercially available medications) and at
least one pharmacist who has special training in compounding
medications. It is our belief that such compounding pharmacies
would produce different responses that demonstrate more effi-
cacious patient care.
Conclusions
Compounding pharmacies play a critical role in com-
pounding medications that are not commercially available for
disorders such as vulvodynia without consensus treatment.
Women’s health issues are the third leading reason for
compounding medications, with 13% (n = 25) of pharmacies
compounding medications for vulvar pain. Given both the
lack of commercially available medications and consensus
guidelines for the treatment of vulvodynia, our results provide
critical knowledge about conventional medical practices.
Focusing on the larger landscape of women’s health, it is
unfortunate that scientifically proven and effective formula-
tions, such as Bendectin, which irrefutably improves the nausea
and vomiting associated with pregnancy, are not the corner-
stone of compounding practice. Conversely, low libido, which
has limited data on mechanisms of action and treatment effi-
cacy, is the third most common indication for compounding.
Based on our study, it seems that we do not completely use the
power of compounding pharmacies to address the unmet needs
of millions of women.
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Corbett et al &Trends in Pharmacy Compounding for Women_s Health
436 *2014 Southern Medical Association
Copyright © 2014 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.
