Women and Herpes Zoster in the United States: Risk and Prevention Management—A Narrative Review

General risk for HZ and HZ complications among women

Identified studies highlighted the increased risk for HZ among women,^{3,6,17,33,43,54} with one meta-analysis reporting a pooled relative risk (95% confidence interval [CI]) of 1.19 (1.14–1.24) for women. ³ One study evaluating HZ frequency by age group and sex observed increases in HZ cases with increasing age, and suggested that the perimenopausal time period may represent a period of increased risk for HZ among women; however, direct evidence linking menopausal hormonal changes to VZV reactivation remains unavailable. ⁴³

Additional studies demonstrated that women had an increased incidence of certain HZ complications, including postherpetic neuralgia (adjusted odds ratio [aOR] for women compared with men [95% CI]: 1.19 [1.10–1.27]), ²⁸ and HZ ophthalmicus (incidence rate ratio for men compared with women [95% CI]: 0.74 [0.72–0.76]). ³⁶

Sociodemographic factors

In addition to differences in HZ risk by sex, other sociodemographic factors, such as care home residence and race and ethnicity, have been associated with HZ risk.^3,33

Chronic conditions

Meta-analyses examining a broad range of risk factors for HZ identified chronic conditions which place patients at a higher risk for HZ, including diabetes, COPD, asthma, cardiovascular diseases, renal disease, and depression.^3,4 While these studies do not all provide sex-specific analyses, several of the chronic conditions identified as risk factors for HZ in the meta-analyses are also prevalent among adult women in the United States, including COPD (7%), ⁶⁴ chronic kidney disease (14%), ⁶⁵ and cardiovascular disease (44%). ⁶⁶ This highlights the importance of understanding the impact that chronic disease can have on women’s risk of developing HZ.

Additional respiratory diseases have also been identified as risk factors for HZ, with an increased HZ risk among women. ⁴¹ A higher risk of HZ in women compared with men was observed for all respiratory conditions assessed, including those with COPD (aOR for male compared with female 0.81 [95% CI: 0.80–0.82]), obstructive sleep apnea (aOR 0.75 [95% CI: 0.74–0.76]), asthma (aOR 0.77 [95% CI: 0.76–0.78]), and lung cancer (aOR 0.77 [95% CI: 0.76–0.78]). ⁴¹

One identified study found that, for both men and women, risk of HZ increased with sleep disorders (adjusted hazard ratio [95% CI]: 1.23 [1.17–1.30]), excluding apnea. ²⁴ While no significant difference in risk was found between men and women, sleep disorders such as insomnia and nonrestorative sleep have been found to be more prevalent among women compared with men.^67,68

Depression was found in one study to be a risk factor for HZ in both women and men, with subgroup analyses showing that the increased risk was only significant in women aged <60 years (adjusted hazard ratio for women aged <40 years [95% CI]: 1.13 [1.02–1.25]; adjusted hazard ratio for women aged 40–59 years [95% CI]: 1.11 [1.04–1.17]). ²³ Stress has also been identified as a potential risk factor for HZ, although the data are mixed, with one identified study reporting a relative HZ incidence (95% CI) of 0.76 (0.54–1.06) during the 90 days following diagnostic code identification of stress compared with a 3-month control period before the stressor, ³² and another reporting an odds ratio (95% CI) of 17.87 (4.43–72.10) using self-reported assessment of stress. ³⁵ A meta-analysis reports a pooled risk ratio (95% CI) of 1.47 (1.03–2.10) for the association of stress and HZ, similarly suggesting mixed findings. ³ Surveys conducted in the United States and globally have demonstrated an increased prevalence of stress among women, indicating the particular importance of stress-related health risks in this population.^69,70

Lastly, chondromalacia patella (runner’s knee) has been associated with an increased risk of HZ in women, ²² although the potential causes linking these two conditions are currently unclear.

Current practices and guidelines

The search identified 18 studies that examined current practices in HZ prevention. The efficacy of RZV for the prevention of HZ has been studied in a phase 3 randomized clinical trial in a population of adults aged ≥50 years. In post hoc analyses, RZV had a 97.0% efficacy against HZ in women. While efficacy against postherpetic neuralgia was numerically higher in women than in men, the difference was not significant. ⁵²

While data on the long-term effectiveness of RZV remain limited, a clinical study reported that the long-term duration of protection from HZ by RZV remains high through 11 years after vaccination. ⁵¹ There are gaps in the evidence landscape regarding real-world effectiveness data of RZV in specific subgroups of women, such as women with chronic conditions (diabetes, COPD, asthma, etc.), women going through menopause, women undergoing cancer treatment, and women with certain cancers. There is evidence to support that RZV has a clinically acceptable safety profile, although a post hoc analysis showed that the incidence of local and general adverse events (all grades and grade 3) was higher among women than men. ²⁷

The identified studies were accompanied by seven U.S. guidelines for HZ vaccination set by organizations including the CDC, ⁵⁷ the American College of Obstetricians and Gynecologists (ACOG), ⁵⁸ the American College of Rheumatology, ⁵⁹ the American Heart Association, ⁶⁰ the American College of Gastroenterology, ⁶¹ the American Society of Clinical Oncology (ASCO), ⁶² and the American Gastroenterological Association ⁶³ (Table 3). Guidelines across organizations follow the CDC guidance of two RZV doses for adults aged ≥50 years and two RZV doses for immunodeficient or immunosuppressed adults aged ≥19 years.^7,8 In one guideline from the National Psoriasis Foundation, experts recommended HZ vaccination for psoriasis and psoriatic arthritis patients aged ≥50 years and younger patients at increased risk. ¹⁸ HZ vaccination is also recommended as a best practice for patients with IBD aged ≥19 years on, or with plans to initiate, immune-modifying therapies.^19,61 Because RZV is a recombinant vaccine, with no live virus, the vaccine was studied in immunocompromised and immunodeficient populations and is indicated and recommended for use in these populations.^61,62 In pregnant women, postexposure prophylaxis is recommended after exposure to VZV or HZ.^29,30

Gaps in prevention

Several studies identified gaps in HZ prevention, including in HZ vaccination uptake in the United States.^26,56 As of 2022, uptake of ≥2 doses of RZV was 17.1% among U.S. adults aged ≥19 years with an indication for vaccination. For U.S. adults aged ≥50 years, uptake was 25.6% and 18.1% for ≥1 RZV dose and ≥2 RZV doses, respectively. ²⁰

Another study demonstrated HZ vaccination disparities by race, with HZ vaccination rates particularly low in Black communities. ⁴⁵ Additionally, an analysis of claims data reported that Black (OR [95% CI]: 0.72 [0.71–0.72]) and Hispanic (OR [95% CI]: 0.78 [0.77–0.78]) patients were less likely to receive RZV compared with White patients. ³⁹ While women were generally more likely to be vaccinated for HZ, ³⁹ disparities in vaccination coverage by race may provide important context for subgroups of women less frequently protected against HZ. These disparities may have a significant medical impact due to other risk factors, such as SLE, that have an increased prevalence in Black and Hispanic female patients. ⁷⁹

HZ vaccination disparities have also been identified by insurance type, ⁸⁰ income,^81,82 and education level^81,82 and have been described among other clinical populations, including those with certain conditions, such as some cancers and asthma.^83,84 These prevention disparities highlight the importance of vaccination strategies that reach patients in the communities that are most impacted by these disparities.

A presentation from the CDC identified barriers to vaccination broadly, such as low awareness of most vaccines, missed opportunities for primary care providers to assess patients’ vaccine needs or offer vaccines recommended for adults, and patients often seeing more than one medical provider. ⁸⁵ Similar barriers, such as low provider awareness of vaccine recommendations among both primary care providers and specialists, have been found in studies specific to HZ vaccination.^86,87 To address these barriers, the CDC recommends routine assessment of patient vaccination status; tailored, well-timed recommendations of vaccines by providers; and acknowledging and addressing patients’ uncertainties. ⁸⁵

In addition to the above recommendations to address barriers to vaccination, uptake could be improved by addressing hesitations regarding vaccination among women. While some evidence suggests women are more likely to be vaccinated for HZ, ³⁹ women are also likely to have hesitations toward vaccination more broadly, which has been demonstrated for coronavirus disease 2019 (COVID-19) and influenza.^88,89 A study addressing COVID-19 vaccine hesitancy among Black women in the United States noted the importance of addressing past instances of medical exploitation, transparency regarding safety information, and culturally respectful communication and promotion of vaccines. ⁹⁰ Another study looking at vaccine hesitancy in a broader population highlighted the importance of patient trust in a health care system; ⁹¹ lower educational attainment was also associated with hesitations surrounding vaccination.^88,92 As vaccine hesitancy has increased, ⁹³ providers should be aware of and ready to address concerns regarding HZ vaccination that may arise among their patients, such as conversations surrounding a patient’s risk for HZ and guidelines for vaccination.

Methods to address gaps in prevention

While not investigated specifically in the context of HZ, digital communications have been used to improve vaccination rates. However, the use of targeted digital communications must be mindful of accessibility, equity and resource limitations, and technical barriers. ⁴⁸ Digital communications may also be utilized through electronic medical records, as this interface is increasingly accessible and utilized by patients for interactions with providers. ⁹⁴

Atypical approaches to vaccination outreach, such as vaccination outside of the typical primary care setting, have also been explored for vaccinations broadly and specific to HZ.^21,26,38 In one review of interventions to improve vaccination coverage, a multifaceted approach of vaccine education and reminders with reinforcement at the point of care was highlighted as an effective way to improve vaccination rates among adults. ²⁶ Other forms of outreach included targeted promotion and vaccination in nontraditional vaccination sites such as community pharmacies, workplaces, faith-based organizations, and schools.^21,38,95

In a qualitative interview study of health care providers and others with expertise in vaccines, positive views of alternative vaccination processes were reported, including vaccination at nontraditional sites and vaccines delivered by nonphysician health professionals. Participants noted that these methods helped increase vaccine access during the COVID-19 pandemic and have shifted attitudes regarding nontraditional vaccine delivery. ⁹⁵ These studies highlight evolving areas of nontraditional delivery of health care that can be utilized for increasing HZ vaccine uptake.

While identified literature did not find current inclusion of HZ prevention in women’s health practices, studies have explored how HZ prevention has successfully been incorporated into other specialty practices, including urology, and allergy and immunology practices.^34,47 Incorporating zoster vaccination delivery into clinical settings where at-risk patients may be most likely to receive care (or otherwise supplying these providers with tools to refer their patients for vaccination if in-office immunization is not available) could be an effective method of reaching patients for adequate HZ prevention. In the oncology space, a more active recognition of the role of immunizations has taken place in recent years, with ASCO issuing immunization guidelines for patients with cancer in 2024. ⁶² Additionally in this field, nurse navigators (nurses who help guide patients through a health care system) have addressed barriers to care and improved treatment adherence, ⁹⁶ and can help integrate vaccination into oncology practices. Given their skillset and number of touchpoints with the patient, there is an opportunity for the navigator to provide education on preventive medicine and help integrate vaccination into the patient’s care as they assist with the coordination of vaccine timing around cancer treatment schedules. This is especially important as there are timing considerations for when to receive vaccinations during cancer treatments, such as chemotherapy cycles.^97,98 This role in the treatment process places oncology nurse navigators in a unique position to identify patients at risk for HZ and optimize vaccination in this population, exemplifying for other specialties how nurse navigators or other patient care navigators may improve HZ prevention in at-risk populations.

For gynecological care, an ACOG Committee Opinion provided immunization implementation strategies tailored to obstetricians/gynecologists (OB/GYNs), which have the potential to be emulated in other provider settings. These include the development of a standardized process for assessing and documenting vaccination status and educating all staff members on the immunization process. ¹⁶ These studies highlight the potential role of OB/GYNs, and other health care providers with a focus on women’s health, in improving health care access and HZ prevention in this population.

OB/GYNs are uniquely positioned to provide preventive care for women as they maintain longitudinal health care relationships that span both the reproductive and postreproductive years. In one study, the majority of patients noted that routine primary care services were available at their OB/GYN office and that they were comfortable receiving routine services from their OB/GYN. ⁹⁹ Additionally, OB/GYNs increasingly act as primary care providers for many women, ¹⁰⁰ and well-woman visits have been highlighted as key opportunities for preventive medicine. ¹⁰¹

Provider vaccine recommendations are a key determinant of subsequent uptake; ¹⁰² thus, encouraging OB/GYNs to view themselves as routine vaccinators or advocates for vaccination and ensuring they are knowledgeable about which of their patients may be at increased risk for HZ and eligible for vaccination may help to further improve HZ prevention among females. Currently, the vaccines routinely provided to nonpregnant patients by OB/GYNs are human papillomavirus, influenza, and tetanus, diphtheria, pertussis (Tdap) vaccines. ¹⁰³ A cooperative agreement led by ACOG working with 19 OB/GYN practices to improve immunization processes identified key strategies for implementing immunizations into the OB/GYN practice workflow, which led to increases in immunization rates and decreases in missed immunization opportunities during the cooperative agreement. These included developing a standard process for assessing and documenting patient vaccination status and periodically assessing immunization rates to determine areas where progress is needed. ¹⁰⁴ An ACOG webinar in conjunction with the CDC also reiterated the importance of routine assessments of vaccination needs at every clinical encounter, strong provider recommendations, administration of the vaccine or referral at the time of recommendation, and documentation of vaccination. ¹⁰⁵

The National Vaccine Advisory Committee has developed Standards for Adult Immunization Practice, which include administering vaccines, if available in-office, or referring patients to a vaccination provider. If a provider does not have a vaccine available in-office, it is advised that they refer patients to private doctor offices, pharmacies, workplaces, community health clinics, health departments, or other community centers, such as schools and faith-based organizations, ¹⁰⁶ as recommendation from a provider is one of the strongest predictors of vaccine uptake. ¹⁰² For OB/GYN practices that are unable to provide vaccinations in-office, ACOG recommends developing a referral system that includes the following: a referral or prescription for a specific vaccine within a specific timeframe, identified locations that offer the vaccine and accept the patient’s insurance, and a plan to follow up with the patient and document their vaccination status. ¹⁰⁷ The implementation of these approaches in an OB/GYN practice setting demonstrates the opportunities for practice-level systematic changes that can make HZ vaccination more accessible for at-risk patients; the broad nature of these approaches also indicates feasibility for other specialty practice settings to foster vaccination and disease prevention for the patients most at risk for HZ.