“Previous studies suggest that altered growth patterns in fetal life and infancy are related to increased risks of cardiovascular diseases in adulthood,” said leading investigator Romy Gonçalves, MSc, who is a PhD candidate in pediatric epidemiology at Erasmus MC, University Medical Center in Rotterdam, the Netherlands. “For example, low birth weight is associated with an unfavorable body composition, higher blood pressure, and higher levels of cholesterol and triglycerides.”

Carotid intima-media thickness and carotid distensibility can both be measured by ultrasound. “The intima-media thickness reflects the inner and middle layer of an artery, and plaque buildup can be identified this way,” Gonçalves told 

Arterial distensibility reflects the elasticity of an artery, according to Gonçalves. “Decreased distensibility is associated with increased risk of arterial wall damage,” she said. “In adults, suboptimal quality of the carotid artery, such as increased carotid intima-media thickness and reduced carotid distensibility, is related to the development of atherosclerosis and cardiovascular diseases. However, this relationship is less clear in children.”

The population-based prospective cohort study was conducted from early fetal life onward in 4,484 offspring (50.4% girls and 57.5% Dutch ethnicity) of women in Rotterdam, the Netherlands, delivering between April 2002 and January 2006.

Estimated fetal weight was measured in the second and third trimester, whereas infant weight was measured at 6, 12 and 24 months.

Follow-up measurements were available for the children at a median age of 9.7 years.

Gestational age at birth was not associated with markers of arterial health; however, a 500 g higher birth weight was linked to significantly increased carotid intima-media thickness and a lower carotid distensibility.

Compared to children with a birth weight of 2500 g to 4500 g, those weighing more than 4500 g had the lowest carotid distensibility.

In addition, compared to children with normal fetal and infant growth, children with normal fetal growth that was followed by accelerated infant growth had the highest carotid intima-media thickness.

The observed associations were mostly explained by childhood body mass index (BMI).

“We hypothesized that children born with low or high birth weight would have increased carotid intima-media thickness and lower carotid distensibility,” Gonçalves said. “But we did not find associations of low birth weight with arterial health.”

The relations of higher fetal weight and infant weight growth with arterial health outcomes are quite novel and indicate that very early-in-life increased weight gain has an effect on the carotid intima-media thickness and carotid distensibility, according to Gonçalves. “Our results suggest that high birth weight followed by higher infant and childhood weight gain is associated with an increased risk of adverse arterial health,” she said.

Gonçalves said further research is needed to examine the extent that adverse arterial health in childhood persists into adulthood. “Our outcomes imply that optimizing growth in early life might be beneficial for arterial health in later life,” she said. “Because our results were partly explained by childhood BMI, preventing high infant weight gain and childhood obesity could aid in reducing adverse arterial health.”

Exemplary prenatal care and information for caregivers and parents on reducing excessive infant weight gain could aid in reducing childhood obesity and subsequent cardiovascular diseases.

“I believe further studies should focus on longitudinal carotid measurements and determining if adverse childhood arterial health persists into adulthood,” Gonçalves said. “Thereby, it could be determined if measurements of childhood arterial health might add to prevention strategies to improve cardiovascular health later in life.”

Gonçalves R, Wiertsema CJ, Silva CCV, et al. Associations of fetal and infant growth patterns with early markers of arterial health in school-aged children. 

. Published online June 29, 2022. doi:10.1001/jamanetworkopen.2022.19225

Articles

Both higher fetal and infant weight growth patterns are linked to early markers of impaired arterial health, according to a study published in JAMA Network Open.

Fetal/infant growth patterns and early markers of arterial health

“Maternal mortality rates in the U.S. are higher than other countries with similar resources; therefore, advancing our understanding of factors that contribute to the maternal death rate is critical,” said principal investigator Heather Frey, MD, MSCI, an associate professor of maternal-fetal medicine at The Ohio State University in Ohio.

Frey noted that obesity, which affects about one-third of pregnant women, is a known risk factor for complications, such as diabetes and hypertension, in pregnancy and is associated with higher rates of mortality in non-pregnant women. “However, some of the previous research is conflicting as to the association between obesity and SMM, so we wanted to better understand this relationship,” she said.

The study accessed the vital records and linked Medicaid claims data in the state of Ohio from January 2012 to December 2017 to determine both mortality and SMM from 20 weeks’ gestation through 1-year postpartum.

In the cohort of 347,497 pregnancies among 276,691 Medicaid beneficiaries, the median maternal age at delivery was 25 years, of whom 60.6% were non-Hispanic White women. The prevalence of maternal obesity was 30.5%.

Composite SMM and/or mortality outcome occurred in 5.3% of pregnancies.

The adjusted risk ratio for an elevated risk of SMM and/or mortality during pregnancy to 1-year postpartum compared to a healthy body mass index (BMI) was 1.07 (95% confidence interval [CI]: 1.03 to 1.11) for overweight (25.0 -- 29.9 BMI); 1.19 (95% CI: 1.13 to 1.24) for class 1 obesity (30.0 -- 34.9 BMI); 1.37 (95% CI: 1.30 to 1.44) for class 2 obesity (35.0 --39.9 BMI); and 1.71 (95% CI: 1.63 to 1.80) for class 3 obesity (≥40.0 BMI).

Results were comparable when the follow-up period was shortened to 42 days postpartum or the delivery hospitalization.

Hypertension mediated 65.1% of the association between obesity and SMM and/or mortality.

“While we were not surprised that hypertension was a mediator, the proportion of the relationship between obesity and the outcome that was explained by hypertension was higher than expected,” Frey told 

. “This highlights the need to develop and implement effective interventions to reduce the risk of hypertensive complications during pregnancy, particularly among obese women.”

The frequency with which women experienced different morbidities within the timeframe also differed by maternal BMI class. For instance, women with increased BMI had high rates of sepsis, while transfusion was the most common indicator of SMM in those with lower BMI when assessed through 42 days postpartum.

“Our data suggest that women who are obese may require increased medical surveillance during pregnancy and, perhaps more importantly, after delivery,” Frey said. “Interventions to improve the delivery of postpartum care and enhance the transition of care from the obstetrician to a primary care provider are needed.”

The study also underscores the importance of identifying and managing hypertensive disorders in pregnant women, particularly those with obesity.

“Unfortunately, efforts to reduce rates of obesity in the U.S. have been largely ineffective on a population level,” Frey said. “On the individual level, though, weight reduction strategies should be employed prior to conception, which starts with appropriate counseling in the preconception period.”

But there is no perfect approach, so discussions and interventions must be tailored to the individual patient, according to Frey. “In the appropriate patient who is interested and motivated to pursue weight-loss surgery, referrals prior to conception should be facilitated,” she said.

Meanwhile, obesity is one of the most common medical comorbidities of pregnancy, and rates of obesity in the pregnant population are expected to continue to increase over the next decade. “Thus, improving our understanding of the risks associated with this condition, then identifying effective interventions to improve the health of pregnant individuals with obesity, are imperative,” Frey said.

1. Frey HA, Ashmead R, Farmer A, et al. Association of prepregnancy body mass index with risk of severe maternal morbidity and mortality among Medicaid beneficiaries. 

Published online June 28, 2022. doi:10.1001/jamanetworkopen.2022.18986

A study published in JAMA Network Open found that maternal prepregnancy obesity in the United States is associated with an elevated risk of severe maternal morbidity (SMM) and/or mortality. 

Prepregnancy BMI and risk of severe maternal morbidity and mortality

Melissa M. Mauskar, MD, is an associate professor of dermatology and obstetrics and gynecology at UT Southwestern Medical Center in Dallas, Texas. She is the founder and director of the Gynecologic Dermatology clinic at UT Southwestern.

Hunter J. Pyle is a fourth-year medical student at the UT Southwestern Medical Center in Dallas, Texas.

Audrey K. Rutherford, MD, is a dermatologist who recently graduated from the dermatology residency program at UT Southwestern in Dallas, Texas. Her current practice is in Salt Lake City, Utah, where she treats women with vulvar dermatoses as well as practices general medical, surgical, and cosmetic dermatology.

Recognizing and appropriately managing common vulvar conditions is essential to preserve patient quality of life and prevent irreversible architectural sequelae. Patients with vulvar dermatoses often report a significant delay from symptom onset to diagnosis. This delay is multifactorial and includes patient and provider reluctance to discuss vulvovaginal or other intimate symptoms. In addition, most women do not examine their vulvas.

Results of a study showed that only 15% of participants were able to correctly sketch vulvar anatomy, 67% had not heard of vulvar self-examination, and 61% approached their genitalia with feelings of shame and embarrassment.

 It is important that providers be comfortable initiating these conversations to prevent diagnostic delay and to give patients accurate information and timely treatment.

Using the correct terms allows providers to develop a wide differential diagnosis 

. An important concept in vulvovaginal dermatology is lichenoid eruption, a diverse group of inflammatory skin diseases sharing common morphology and/or histopathology. Distinguishing among the various lichenoid conditions of the genitalia, including vulvar lichen sclerosus (VLS), vulvovaginal lichen planus (VLP), and vulvar lichen simplex chronicus (LSC), is important because optimal treatments vary. 

Figure 1. Select Dermatology Terminology. 

Although all 3 conditions may present primarily with pain or pruritus, features such as anatomic involvement, risk factors, and associations may differ. VLS and VLP are primary cutaneous disorders, whereas vulvar LSC is a secondary skin condition resulting from another underlying dermatosis, infection, or psychological or neurologic condition. VLS primarily affects external genitalia, whereas VLP may affect both the vulva and vagina.

VLS is a chronic, often progressive dermatologic condition that involves the anogenital region. The prevalence of VLS is not well established, though it is likely an underrecognized and undermanaged condition. Results of large cohort study showed an estimated prevalence in the United States of 0.05%, with 79% of diagnoses in women between the ages of 45 and 65 years but 16% of diagnoses in women between the ages of 18 and 44 years.

 Most patients present with vulvar pain, pruritus, or irritation, but patients may be asymptomatic. Patients eventually diagnosed with VLS may have yeast infections for years 

Figure 2-1. Pustules on an erythematous base in a patient with vulvovaginal candidiasis.

Figure 2-2. Hypopigmented macules in a patient with vulvar lichen sclerosus.

Early detection of VLS is critical to preventing irreversible architectural sequelae and vulvar squamous cell carcinoma (SCC). Skin changes that may be evident upon vulvar inspection include white, atrophic papules that may coalesce into plaques, often affecting the labia minora or majora 

Figure 2-3. Typical hypopigmented tissue paper wrinkling in a patient with vulvar lichen sclerosus. (Figures provided by author)

Early VLS may have a nonspecific presentation, so a high degree of suspicion must be maintained. Varying degrees of architectural change may be present in later disease stages. It is important to note indurations and small erosions, which could be signs of SCC, even in younger patients. First-line treatment is early use of a superpotent topical corticosteroid with continued topical corticosteroid for maintenance therapy. Patient education emphasizing treatment adherence is critical. In a study that spanned 8 years, patients adherent to topical corticosteroid treatment did not develop SCC or precursor vulvar intraepithelial neoplasia (VIN), and adhesions and scarring developed in only 3% of patients.

 Reports of symptomatic control also were higher in adherent patients. In contrast, in patients only partially adherent with treatment, 5% developed SCC or VIN and 40% developed adhesions
and scarring.

VLP is an inflammatory condition and subtype of lichen planus (LP) that most commonly affects women between 50 and 60 years of age.

 Although the incidence and prevalence of VLP is unknown, most women with LP have genital lesions.

 Most frequently, patients will present with soreness, pruritus, or genital burning. 

Allergic and irritant contact dermatitis of the vulva

Allergic and irritant contact dermatitis (ACD/ICD) frequently occur concomitantly with other vulvar conditions as preexisting dermatosis impairs skin barrier function. In patients with vulvar ACD, the most common concomitant vulvar diagnoses are VLS followed by LSC.

 This may complicate the clinical picture and lead to diagnostic and management delays. Therefore, vulvar ACD/ICD should be considered when patients with vulvar disease are not improving with standard treatment.

Figure 2-4. Introitus erosions with surrounding lacy/reticular border in a patient with erosive vulvovaginal lichen planus.

Vulvar ICD may occur acutely or, more commonly, chronically. Symptoms in vulvar ACD may become apparent 1 to 2 days after allergen exposure, but commonly the exposure is unrecognized and may only slowly produce symptoms and eruption. This frequently leads to difficulty in identifying the culprit allergen. Patients with ACD/ICD often present with nonspecific vulvar pruritus or burning. Skin changes in vulvar ACD/ICD are similar and include erythema, edema, vesicles, bullae, and oozing. Thus, clinical differentiation of vulvar ACD/ICD is not reliable. The diagnosis of vulvar ICD is based on history and establishment of a potential irritant, whereas vulvar ACD may be established with patch testing.

Patients with vulvovaginal symptoms have often tried various topicals for symptom resolution before seeking medical attention. Common vulvar irritants include body fluids, hygiene or personal care products, heat, excessive bathing, medications, soaps, and detergents.

 The most commonly identified allergens in ACD are fragrances, preservatives, and medications including neomycin and topical anesthetics.

 Patients may have an allergy to topical corticosteroids,

 which are an important first-line treatment for many vulvar dermatoses 

ACD/ICD treatment includes discontinuing potential irritants and allergens, using petroleum on erosions, and educating patients. Patients should be counseled on the importance of cleaning the vulva with lukewarm water without harsh or fragranced soaps, cleansers, or detergents, and using sitz baths for additional symptomatic relief. Topical corticosteroid ointments may be used in severe or chronic disease, and antihistamines may be used for pruritus. Patients may benefit from a dermatology referral for patch testing to identify possible culprit allergens, which is a more appropriate testing modality to identify contact allergens than the skin prick test commonly performed by allergist physicians.

Figure 2-5. Erythematous thickened, corrugated plaques with accentuation of skin markings on the labia majora and inguinal folds characteristic of lichenification found in lichen simplex chronicus. There is also a thin white scale on the leftinguinal fold. (Figures provided by author).

LSC is a reactive skin disorder secondary to chronic skin rubbing or scratching, often in response to persistent pruritus or irritation, regardless of primary problem. It results in secondary changes of skin including thickening and lichenification 

, with a moderately well-defined scaly plaque. Patients with other vulvar dermatoses often develop LSC in response to chronic scratching. Patients with LSC can pose a diagnostic challenge as primary skin conditions cannot be appropriately diagnosed until there is improvement in LSC symptoms and cutaneous changes. LSC is typically a clinical diagnosis, and management centers on disrupting the itch-scratch cycle, in which pruritus leads to scratching, which perpetuates and worsens inflammation. First-line medical treatment often includes a short course of medium-potency topical corticosteroid to promote active lesion resolution. Upon treatment of LSC, an underlying primary vulvovaginal dermatosis may be more readily identifiable and addressed.

Genitourinary syndrome of menopause (GSM), formerly called vulvovaginal atrophy or atrophic vaginitis, refers to a collection of signs and symptoms that occur in menopausal women secondary to decreased stimulation of estrogen-sensitive tissues, including the vulva, vagina, urethra, and bladder. GSM is very common. In fact, vulvovaginal symptoms occur in 39% to 51% of postmenopausal women, with the majority having moderate to severe symptoms, and one-third stopping sexual activity because of their symptoms.

 Unfortunately, many women do not recognize vulvovaginal atrophy and are reluctant to discuss vaginal or sexual symptoms with health care professionals.16 Most women with GSM believe that their vaginal symptoms are a normal part of aging.

 Symptoms seen in GSM include genital dryness, discomfort, burning, dyspareunia, dysuria, urinary incontinence, and recurrent urinary tract infections. Physical changes may include a vaginal epithelium that is a paler pink hue with decreased rugation, diminished pubic hair, decreased turgor and elasticity of the vulva, and minimization of the labia minora. GSM is a clinical diagnosis. Women have a strong desire for health care professionals to initiate conversations regarding GSM.16 First-line treatment includes vaginal moisturizers, personal lubricants, and low-dose vaginal estrogen. Of note, multiple studies have shown no increase in risk of cardiovascular disease or cancer with low-dose vaginal estrogen use.

 In addition, low-dose vaginal estrogen has minimal systemic absorption and does not increase plasma estradiol to premenopausal levels, study results show.19 In cases of advanced symptoms, pelvic physical therapy may be beneficial, particularly for urinary incontinence
and dyspareunia.

Talking to a patient about vulvovaginal concerns

Intake Questionnaire, Select Example Questions

Before the clinic visit, intake questionnaires provide the patient with space to answer sensitive questions 

. During evaluation, review the patient’s hygienic practices and product usage. Patients should be asked whether they engage in a vulvar washing or cleaning practice. In our society, where patients unfortunately are taught that their vulvas are unclean, patients may believe that symptom resolution is only a matter of washing more thoroughly or vigorously. Such aggressive cleaning can lead to recalcitrant vulvar disease. Also note any products that patients may be using after toileting, such as wet wipes, that could lead to vulvar ACD/ICD. In reviewing medication and product usage, document the location of genital application. This can be completed during the exam with direct patient demonstrations by having the patient apply plain petroleum jelly to herself as if it were medication. Frequently patients do not directly visualize where they are applying products or are using inappropriate amounts of topical therapies, which may lead to inadequate undertreatment of some locations or inappropriate overtreatment of others.

Prior to physical examination, have a chaperone or assistant enter the room and obtain patient verbal consent. Patient communication before and during examination increases participation and facilitates patient control and autonomy. For new patients or those with notable vaginal discharge, obtain wet and KOH preps to assess for infection and diagnostic clues (such as parabasal cells in GSM). Using a hand mirror allows patients to see where medication should be applied. The patient’s position on the examination table is crucial to optimize their viewing of medication application. The patient may use petroleum jelly at this point to demonstrate how they apply medication, which provides another opportunity for redirection or educational intervention if application is incorrect.

A vulvar biopsy may be needed to diagnose conditions when the clinical diagnosis is uncertain. Biopsy type depends on clinical impression. Shave biopsy may be used for suspected VLS or VLP, whereas punch biopsy should always be used for ulcerations or suspected malignancy. Get a biopsy for suspected VLS in the crinkly area, suspected VLP at the edge of defect such that normal skin is included, and suspected malignancy in the center or border of the lesion.

During the management portion of the clinic visit, patient handouts and literature reinforce information covered during the clinic visit, and a photograph of the patient’s genital area may be obtained and annotated for patient medical or personal records after patient consent. Reviewing this photograph with the patient allows them to clearly see affected areas and visualize where topical medications should be applied. The photograph may be annotated to specify the location, amount, and frequency of topical medication application 

Figure 5. Annotated patient photograph (Figure provided by author)

After the clinic visit, give the patient this annotated photograph to take home to use as a guide for treatment application. At future clinic visits, this initial photograph may be reviewed to demonstrate clinical improvement or changes, and a new photograph may be taken and annotated to help communicate any necessary adjustments to areas of topical application.

At subsequent visits, the differential should be revisited, especially if the patient is not improving, as treatment failure may be the result of missed diagnoses. A patient may have more than 1 condition concurrently affecting the vulva and vagina, which may be causal or only associated with one another. It is equally important to rediscuss exposures, hygiene, and medications, as patient habits may evolve and complicate conditions or be misinterpreted as flares of primary processes when instead they represent a new secondary or concomitant process, such as development of new ICD. 

1.Preti M, Selk A, Stockdale C, et al. Knowledge of vulvar anatomy and self-examination in a sample of Italian women. 

. 2021;25(2):166-171. doi:10.1097/LGT.0000000000000585

2.Melnick LE, Steuer AB, Bieber AK, Wong PW, Pomeranz MK. Lichen sclerosus among women in the United States. 

. 2020;6(4):260-262. doi:10.1016/j.ijwd.2020.05.001

3.Lee A, Bradford J, Fischer G. Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women. 

. 2015;151(10):1061-1067. doi:10.1001/jamadermatol.2015.0643

4.Cooper SM, Wojnarowska F. Influence of treatment of erosive lichen planus of the vulva on its prognosis. 

. 2006;142(3):289-294. doi:10.1001/archderm.142.3.289

5.Kennedy CM, Galask RP. Erosive vulvar lichen planus: retrospective review of characteristics and outcomes in 113 patients seen in a vulvar specialty clinic. 

6.Lewis FM, Shah M, Harrington CI. Vulval involvement in lichen planus: a study of 37 women. 

7.Zendell K, Edwards L. Lichen sclerosus with vaginal involvement: report of 2 cases and review of the literature. 

. 2013;149(10):1199-1202. doi:10.1001/jamadermatol.2013.4885

8.Bradford J, Fischer G. Management of vulvovaginal lichen planus: a new approach. 

. 2013;17(1):28-32. doi:10.1097/LGT.0b013e318258bf5b

9.Fairchild PS, Haefner HK. Surgical management of vulvovaginal agglutination due to lichen planus. 

. 2016;214(2):289.e1-289.e2. doi:10.1016/j.ajog.2015.08.070

10.Trivedi MK, Woodruff CM, Kornik R, Botto N. Patch testing in vulvar allergic contact dermatitis. 

. 2018;29(2):95-96. doi:10.1097/DER.0000000000000345

11.Schlosser BJ. Contact dermatitis of the vulva. 

. 2010;28(4):697-706. doi:10.1016/j.det.2010.08.006

12.Warshaw EM, Furda LM, Maibach HI, et al. Anogenital dermatitis in patients referred for patch testing: retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 1994-2004. 

. 2008;144(6):749-755. doi:10.1001/archderm.144.6.749

13.Lewis FM, Shah M, Gawkrodger DJ. Contact sensitivity in pruritus vulvae: patch test results and clinical outcome. 

14.Dumycz K, Osinka K, Feleszko W. Contact allergens in topical corticosteroid vehicles: analysis of product composition. 

. 2017;76(4):254-255. doi:10.1111/cod.12693

15.Haefner H. The gynecologist’s guide to steroid use. February 27, 2015. Accessed July 11, 2022. https://dokumen.tips/documents/gynecologists-guide-steroid-useppt-2242015-2-steroids-a-manage-not-cure-dermatologic.html

16.Krychman M, Graham S, Bernick B, Mirkin S, Kingsberg SA. The Women’s EMPOWER survey: women’s knowledge and awareness of treatment options for vulvar and vaginal atrophy remains inadequate. 

. 2017;14(3):425-433. doi:10.1016/j.jsxm.2017.01.011

17.Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. 

. 2018;26(6):603-610. doi:10.1097/GME.0000000000001284

18.Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative Observational Study. 

. 2018;25(1):11-20. doi:10.1097/GME.0000000000000956

19.Santen RJ. Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels. 

. 2015;18(2):121-134. doi:10.3109/13697137.2014.947254

20.Edwards L. Patient information packet. Mid-Charlotte Dermatology and Research Southeast Vulvar Clinic. Accessed July 11, 2022. https://nebula.wsimg.com/70af598099d980b624b0e104369f19c6?AccessKeyId=B78439C8610A1092E451&disposition=0&alloworigin=1

Correct terms and education can help normalize the conversation for patients.


Essentials of vulvovaginal dermatology

On April 26, 2022, the FDA approved inhibitor that targets CYP51 and is available as oteseconazole (Vivjoa), an oral azole antifungal indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in women with a history of RVVC who are not of reproductive potential.1 Oteseconazole is an azole metalloenzyme a single-drug regimen or in combination with fluconazole. Antifungal therapy may be instituted before the results of the cultures are known and adjusted accordingly when results become available.2

The first 2 clinical trials (NCT03562156 and NCT03561701)3,4 included a total of 656 adults and postmenarcheal pediatric women with RVVC who were randomly assigned to receive either oteseconazole only or placebo.

A third trial (NCT03840616)5 evaluated safety of oteseconazole vs fluconazole and placebo in 219 adults and postmenarcheal pediatric women with RVVC.2

Trials 1 and 2 each included an open-label induction phase and an 11-week maintenance phase. During the induction phase, participants received 3 sequential doses of fluconazole 150 mg every 72 hours on days 1, 4, and 7. At 14 days following the first fluconazole dose, if the acute VVC episode was resolved, participants were randomly assigned 2:1 to receive either oteseconazole 150 mg or placebo for 7 days, followed by 11 weekly doses during the maintenance phase; 326 and 330 patients, respectively, entered this phase. Primary efficacy end points were the proportion of patients with greater than or equal to 1 culture-verified acute VVC episode during the maintenance phase through week 48.3 The average percentage of patients with an acute VVC episode was lower in the oteseconazole group vs the placebo group in both trials (6.7% vs 42.8% and 3.9% vs 39.4%, respectively).2

Trial 3 evaluated the efficacy and safety of oteseconazole vs fluconazole and placebo. This trial also included induction and maintenance phases. Participants received a total dose of oteseconazole 150 mg over 2 days (600 mg [4 × 150 mg] on day 1 and 450 mg [3 × 150 mg] on day 2) or 3 sequential doses of fluconazole 150 mg every 72 hours on days 1, 4, and 7. Patients returned 14 days after the first dose and moved to the maintenance phase if the acute VVC episode was resolved. During the maintenance phase, patients received oteseconazole 150 mg or placebo weekly for 11 weeks.5 The primary efficacy end point was the proportion of patients with greater than or equal to 1 culture-verified acute VVC during the maintenance phase or who failed to clear their infection during the induction phase. The average percentage of patients with greater than or equal to 1 culture was lower in the oteseconazole group vs the fluconazole and placebo group (10.3% vs 42.9%, respectively).2

The most frequently reported adverse events were headache (7.4%) and nausea (3.6%). One patient discontinued therapy because of allergic dermatitis. Because of the risk of embryo-fetal toxicity, oteseconazole is contraindicated in women of reproductive potential and in women who are pregnant or lactating. Medication administration in conjunction with a high-fat, high-calorie meal increased concentrations, but no significant differences were observed with a low- fat, low-calorie meal.2

The oteseconazole-only dosage regimen is initiated as a 600-mg capsule on day 1 and 450 mg on day 2, each as a single dose. The next dose is administered on day 14 as a 150-mg capsule once weekly for 11 weeks.

The fluconazole/oteseconazole dosage regimen is initiated with fluconazole 150 mg orally on days 1, 4, and 7, followed by oteseconazole 150 mg once daily for 7 days, starting on day 14 through day 20. After day 20, the next oteseconazole dose is administered on day 28 as a 150-mg capsule once weekly for 11 weeks. Oteseconazole must be taken with food.2

FDA approves Mycovia Pharmaceuticals’ VIVJOA (oteseconazole), the first and only FDA-approved medication for recurrent vulvovaginal candidiasis (chronic yeast infection). News release. Mycovia Pharmaceuticals; April 28, 2022. Accessed July 12, 2022. 

https://mycovia.com/wp-content/uploads/2022/04/FINAL-Press-Release_04.28.22.pdf

Vivjoa. Prescribing information. Mycovia Pharmaceuticals Inc; 2022. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215888s000lbl.pdf

A study of oral oteseconazole for the treatment of patients with recurrent vaginal candidiasis (yeast infection)(VIOLET). ClinicalTrails.gov. Updated April 6, 2022. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03562156

A study of oral oteseconazole (VT-1161) for the treatment of patients with recurrent vaginal candidiasis (yeast infection) (VIOLET). ClinicalTrials.gov. Updated December 20, 2021. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03561701

Study of oral oteseconazole (VT-1161) for acute yeast infections in patients with recurrent yeast infections (ultraVIOLET). ClinicalTrials.gov. Updated February 4, 2022. Accessed July 12, 2022. 

https://clinicaltrials.gov/ct2/show/NCT03840616

Oteseconazole is a treatment option for those living with a previously unmet medical need.

Vivjoa approved for recurrent vulvovaginal candidiasis

 and joined the MJH Life Sciences team in December 2019. She graduated from Youngstown State University in 2019 with a bachelor's degree in journalism and a minor in political science. Prior to graduating, Morgan worked as the editor-in-chief of her college newspaper. She went on to work as an assignment editor at a broadcast news station in Youngstown, Ohio before joining 

Myovant announced the US Food and Drug Administration (FDA) has approved relugolix combination tablets (Myfembree; Myovant Sciences and Pfizer) for the treatment of moderate-to-severe endometriosis-associated pain.

Previously, Myfembree was only approved for the management of uterine fibroid-related heavy menstrual bleeding in premenopausal women.

“This approval is an important milestone reflecting Pfizer and Myovant’s commitment to women’s health in areas of significant unmet need,” said James Rusnak, MD, PhD, senior vice president, chief development officer, Internal Medicine and Hospital, Global Product Development at Pfizer. “We look forward to making Myfembree available to women with endometriosis and broadening their options in managing this complex disorder.”

This decision by the FDA is supported by 

 from two phase 3 studies (SPIRIT 1 and SPIRIT 2) investigating the combination tablet for treatment of dysmenorrhea.

In both studies, 75% of women using the once-daily relugolix combination therapy experienced a significant reduction in dysmenorrhea, compared to 27% and 30% of women in the placebo groups at Week 24, respectively (both p < 0.0001). Relugolix combination therapy also significantly reduced non-menstrual pelvic pain in 59% and 66% of women, compared to 40% and 43% in the placebo groups (p <0.0001).

In SPIRIT 1 and 2, the relugolix combination therapy group also showed reductions in dyspareunia and opioid use compared to the placebo groups. Additionally, more women undergoing relugolix combination therapy were opioid free at Week 24 compared with placebo (86% and 82% vs 76% and 66%, respectively).

The most frequently reported adverse events by women in both the relugolix combination therapy and placebo groups included headaches, nasopharyngitis, and hot flashes.

"The data from the SPIRIT studies showed the clinical benefit that relugolix combination therapy can have on moderate to severe pain associated with endometriosis and how it can impact patients,” said Linda Giudice, MD, PhD, distinguished professor at the University of California, San Francisco (UCSF), and chair, SPIRIT Program Steering Committee. “This newly approved option for patients with pain from endometriosis offers the convenience of one pill taken once daily with a mean change in bone mineral density of <1% that did not appear to worsen at 12 months of treatment; however, monitoring is recommended.”

Myfembree is now available with a prescription to patients with moderate-to-severe pain associated with endometriosis.

1. Myovant Sciences and Pfizer Receive U.S. FDA Approval of MYFEMBREE, a Once-Daily Treatment for the Management of Moderate to Severe Pain Associated With Endometriosis. Myovant Sciences. August 5, 2022. Accessed August 5, 2022. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-receive-us-fda-approval-myfembreer

2. Giudice LC, As-Sanie S, Arjona Ferreira JC, et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomized, double-blind, studies (SPIRIT 1 and 2). 

. 2022;399(10343):2267-2279. doi:10.1016/s0140-6736(22)00622-5

Myovant Sciences and Pfizer announces the US Food and Drug Administration has approved Myfembree (relugolix combination tablets) for the once-daily treatment of moderate-to-severe endometriosis-associated pain. 

FDA approves Myfembree for endometriosis pain

The monkeypox vaccine Jynneos has emergency approval for use with adult patients determined to be at high risk for 

The U.S. Food and Drug Administration (FDA) announced an 

 (EUA) for Jynneos (Modified Vaccinia Ankara vaccine), first approved in 2019 for prevention of smallpox and monkeypox disease in adults aged 18 years and older. The EUA for a fraction of the dose administered by intradermal injection, will increase the total number of doses available by up to five-fold, according to the FDA’s Aug. 9 announcement.

 in patients younger than 18 years and determined to be at high risk of monkeypox infection. They will receive the vaccine by subcutaneous injection.

In both cases, two doses of the vaccine, given 28 days apart, are needed because there is no data to indicate one dose will provide long-lasting protection needed to control the current outbreak, according to FDA.

“In recent weeks the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand,” FDA Commissioner Robert M. Califf, MD, said in the agency’s announcement. “The FDA quickly explored other scientifically appropriate options to facilitate access to the vaccine for all impacted individuals. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so.”

A 2015 clinical study of the vaccine evaluated the two-dose series given intradermally compared to subcutaneously. Patients who received it intradermally received 1/5 the volume of those who received it subcutaneously, and both forms produced similar immune responses, according to FDA.

Patients with intradermal injection reported more redness, firmness, itchiness and swelling at the injection site, but less pain, and the side effects were manageable. “The FDA has determined that the known and potential benefits of Jynneos outweigh the known and potential risks for the authorized uses,” the agency’s announcement said.

The Jynneos vaccine involves 0.5mL for the subcutaneous administration, but 0.1mL for intradermal administration under the EUA, according to the federal 

Centers for Disease Control and Prevention

Another vaccine, ACAM2000, is approved for immunization against smallpox and is available for use against monkeypox under an Expanded Access Investigational New Drug (EA-IND) protocol, according to CDC.

For both vaccines, no data are available on the efficacy or effectiveness in the current outbreak. People who are vaccinated should continue to take steps to protect themselves against infection, including avoiding close, skin-to-skin contact and intimate contact with someone who has monkeypox, according to CDC.

As of Aug. 10, FDA was not recommending vaccination for the general public, but for 

 to monkeypox. “Currently, a high rate of the known cases in the U.S. are among gay and bisexual men and transgender and non-binary people, but this virus is not limited by sexuality or gender,” FDA said.

/orthopoxvirus cases, with 2,104 cases in New York, 1,310 cases in California, and 976 cases in Florida, leading the national count, according to CDC.

This article originally appeared on Medical Economics®. 

Image credit: The U.S. Food and Drug Administration published this image of a colorized scanning electron micrograph of monkeypox virus (orange) on the surface of infected VERO E6 cells (green). The image is credited to the National Institute of Allergy and Infectious Diseases.

Smaller dose given by intradermal injection creates five-fold increase in total supply, FDA says.

Monkeypox vaccine gets emergency approval to increase vaccine supply

Medical and insurance organizations generally reacted favorably to the Senate’s Aug. 7 approval of the 

This week, the House of Representatives is expected to begin deliberating on the law, which has at least three national-level effects on health care:

Medicare will be allowed to negotiate drug prices.

Seniors’ out-of-pocket spending on prescription drugs will be capped at $2,000.

Subsidies will continue for patients purchasing health insurance through the Affordable Care Act Marketplace.

The American College of Physicians (ACP) praised the legislation to improve access to health care and improve health for all Americans, President Ryan, D Mire, MD, FACP, said in a 

“We are glad to see that the final version of the legislation still includes many of the important provisions that we 

 when the agreement was announced,” Mire said. “Subsidies for health insurance plans under the Affordable Care Act will be extended for three additional years, Medicare will now be allowed to negotiate lower drug prices with manufacturers, and the legislation will help to reduce carbon pollution and advance clean energy solutions. We are also encouraged that the legislation will cap insulin costs for Medicare beneficiaries, allowing our senior patients to more easily afford this life-saving medication. We look forward to the House taking up the bill and call on them to swiftly pass it.”

The Association of American Medical Colleges (AAMC) said the legislation will invest $64 billion for the ACA insurance subsidies.

“As the COVID-19 pandemic has highlighted many disparities in access to coverage and care, we commend senators for agreeing on a bill that will allow patients and families to maintain access to affordable coverage, empowering them to seek care before treatable conditions become more complicated and costly,” AAMC President David J. Skorton, MD, said in a 

. “Additionally, the high cost of prescription drugs often prevents patients from obtaining the medications they need. We support efforts to lower drugs costs and increase access to affordable medications.”

Louise Norris, health policy analyst for consultant 

“This is excellent news for the 13 million Americans who rely on premium subsidies to make marketplace health coverage affordable. Larger and more widely available subsidies have led to record-high marketplace enrollment,” Norris said. “Without action from Congress, millions of people will likely see their subsidies decrease or disappear in 2023, and 3 million current enrollees might lose their coverage altogether. The Senate’s vote to pass this legislation is a step toward ensuring these hard working Americans will still be able to afford their health coverage next year, and we hope to see it pass quickly in the House.”

The Endocrine Society issued a statement praising the IRA for addressing high insulin costs. More than 7 million people rely on insulin to manage diabetes and live, and the U.S. Centers for Disease Control and Prevention logged 37.3 million people with diabetes – 11 % of the nation’s population.

Insulin nearly tripled in price from 2002 to 2013, with the upward trend continuing.

The Endocrine Society noted the Senate missed an important opportunity to also help children and adults with type 1 diabetes when 43 Republicans voted against including a provision that would have capped out-of-pocket costs for individuals with private insurance, that the society supported.

, President Joe Biden led with the potential health care benefits, noting the IRA will lower the costs of prescription drugs and health insurance, along with other provisions of the bill. Biden said he ran for the post “promising to make government work for working families again, and that is what this bill does – period.”

 the new law will have a negative effect on innovation in the pharmaceutical industry, which in turn will have consequences for health of Americans.

Using “savings” from drug price controls to cover ACA insurance “would lead to a massive loss of life, due to foregone medical innovation, and a reduction in the quality of care, due to the government gaining more control over people’s insurance coverage,” former White House economic adviser 

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FDA approves Myfembree for endometriosis pain