General Gynecology | Links Medicus Content Curation & Alerts in Medicine

RCT: Infrequent Zoledronate Infusions Reduce Vertebral Fractures in Early Postmenopausal Women Without Osteoporosis

18 Jan, 2025 | 16:48h | UTC

Background: Osteoporosis prevention typically targets older, higher-risk populations with significantly reduced bone mineral density (BMD). However, many fragility fractures occur in women who do not meet the traditional diagnostic threshold for osteoporosis (T score ≤ –2.5). This study investigated whether infrequent administration of zoledronate could prevent vertebral fractures in early postmenopausal women (50 to 60 years of age) who have BMD values between normal and osteoporotic ranges.

Objective: To determine if administering intravenous zoledronate once at baseline—and again 5 years later—could reduce the incidence of morphometric vertebral fractures and other fracture types over a 10-year period in early postmenopausal women without osteoporosis.

Methods:

Design: A 10-year, prospective, double-blind, randomized, placebo-controlled trial.
Population: 1054 women (mean age 56.0) within 10 years post-menopause, with lumbar spine or hip T scores <0 but >–2.5, recruited from the electoral roll in Auckland, New Zealand.
Interventions: Participants were randomly assigned (1:1:1) to receive:
1. Zoledronate 5 mg at baseline and again at Year 5 (zoledronate–zoledronate)
2. Zoledronate 5 mg at baseline and placebo at Year 5 (zoledronate–placebo)
3. Placebo infusions at baseline and Year 5 (placebo–placebo)
Follow-up: 10 years, with repeated BMD and spine X-ray assessments at baseline, Year 5, and Year 10.
Primary Endpoint: Incidence of new morphometric vertebral fractures, defined by semiquantitative radiographic methods.
Secondary Endpoints: Fragility fracture, any fracture, major osteoporotic fracture, changes in BMD, and bone-turnover markers.

Results:

Vertebral Fractures: Over 10 years, 6.3% of participants in the zoledronate–zoledronate group and 6.6% in the zoledronate–placebo group experienced a new morphometric vertebral fracture, versus 11.1% in placebo–placebo. After imputation, the relative risks versus placebo–placebo were 0.56 (95% CI, 0.34–0.92; p=0.04) and 0.59 (95% CI, 0.36–0.97; p=0.08), respectively.
Other Fractures: The zoledronate–zoledronate group had a 30% reduced risk of any fracture (RR, 0.70; 95% CI, 0.56–0.88), and zoledronate–placebo showed a 23% reduction (RR, 0.77; 95% CI, 0.62–0.97), both compared with placebo–placebo.
Bone Mineral Density: At Year 10, the zoledronate–zoledronate group had sustained BMD gains (~7–9 percentage points above placebo), whereas the zoledronate–placebo group retained a moderate advantage (~5–6 percentage points above placebo).
Bone-Turnover Markers: Markers remained suppressed in the zoledronate–zoledronate group through Year 10, while in the zoledronate–placebo group, they gradually rose after Year 5 but stayed below baseline levels.
Safety: Few adverse events were reported. Uveitis or episcleritis after the first infusion occurred in 1.1% of zoledronate recipients. No cases of osteonecrosis of the jaw or atypical femoral fractures were observed.

Conclusions: A single 5-mg dose of zoledronate, with an optional additional dose at five years, reduced the incidence of morphometric vertebral fractures and helped preserve BMD in younger postmenopausal women without osteoporosis. Both zoledronate regimens showed notable fracture-risk reductions and sustained effects on bone turnover.

Implications for Practice: These findings extend the potential role of zoledronate in fracture prevention to younger, early postmenopausal women without osteoporosis. Infrequent infusions are attractive because of their prolonged pharmacologic action and generally favorable safety profile. However, caution is warranted before broadly implementing this strategy for all postmenopausal women, as the data come from a relatively homogenous population and do not address other risk factors or comorbidities. Real-world adherence, healthcare resource allocation, and patient preferences must all be considered. Moreover, further evaluation of cost-effectiveness is essential, especially if expanding use to large populations. Longer follow-up in broader and more diverse groups may reveal less common adverse events that were not detected in this trial. Clinicians should therefore weigh individual risk–benefit profiles and await additional data before making universal recommendations.

Study Strengths and Limitations:

Strengths: The trial’s 10-year duration, double-blind design, and high retention rate enhance its internal validity. Using radiographic assessments for vertebral fractures adds objectivity and robustness.
Limitations: The trial predominantly involved healthy, early postmenopausal women of European descent, limiting the applicability of the findings to other ethnicities, older populations, or those with complex comorbidities. Only two zoledronate infusions at a five-year interval were evaluated, leaving the optimal dosing frequency unresolved. Further, while adverse events appeared uncommon here, the sample size and population profile may not adequately capture rare or long-latency adverse outcomes.

Future Research: Larger trials in more diverse demographic and clinical settings are necessary to determine whether infrequent zoledronate can safely and effectively reduce fracture risk across broader patient groups. Studies comparing different dosing schedules, as well as investigations into cost-effectiveness and logistics of administration, would be highly valuable. Longer-term surveillance in real-world cohorts should help clarify the incidence of uncommon adverse events. Ultimately, such additional evidence will guide whether infrequent zoledronate infusions might be integrated into routine practice for fracture prevention in postmenopausal women without osteoporosis.

Reference:

Bolland MJ, Nisa Z, Mellar A, et al. Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. New England Journal of Medicine. 2025;392:239-248. DOI: http://doi.org/10.1056/NEJMoa2407031
Chapurlat R. Infrequent Zoledronate — Small Individual Gain, Larger Population Gain. New England Journal of Medicine. 2025;392:281-283. DOI: http://doi.org/10.1056/NEJMe2415376

Clinical Overview of Cervical Cancer: Screening, Treatment, and Future Directions

6 Jan, 2025 | 10:00h | UTC

Introduction: This summary provides a concise review of a comprehensive guideline on cervical cancer, covering its epidemiology, risk factors, clinical presentation, and current therapeutic strategies. The aim is to highlight best practices for prevention, screening, and management, as well as emerging treatments that may shift the standard of care.

Key Recommendations:

Prevention and Screening
- Encourage HPV vaccination before exposure, ideally in adolescence.
- Perform regular screening with a Papanicolaou test, HPV testing, or both, based on national guidelines.
- Use colposcopy and directed biopsies for women with abnormal screening results.
Early-Stage Disease (FIGO IA to IB2)
- Offer radical hysterectomy plus pelvic lymphadenectomy; ovarian preservation may be considered for endocrine benefits.
- Less radical surgery (simple hysterectomy or conization) is now acceptable for smaller tumors (<2 cm) confirmed by imaging and pathology.
- In selected cases, fertility-sparing radical trachelectomy can be considered, though the SHAPE trial supports more conservative approaches for certain early tumors.
Locally Advanced Disease (FIGO IB3 to IVA)
- Recommend concurrent chemoradiation therapy (daily external-beam radiotherapy, brachytherapy, and weekly cisplatin).
- Immunotherapy (pembrolizumab) is approved in combination with chemoradiation for FIGO III to IVA disease, demonstrating improved survival.
- Ensure treatment completion within optimal time frames to maximize therapeutic efficacy.
Pelvic Exenteration
- Consider total pelvic exenteration for isolated central recurrence in patients without distant disease.
- Thorough psychosocial evaluation is critical before proceeding with this extensive procedure.
Metastatic or Recurrent Disease (First-Line Therapy)
- A platinum-based regimen (cisplatin or carboplatin) combined with paclitaxel, with or without bevacizumab, remains a standard option.
- For PD-L1–positive tumors, adding pembrolizumab has shown a survival advantage.
- Bispecific immunotherapy and novel therapeutic regimens are under investigation to improve outcomes further.
Second-Line Therapy
- Tissue factor–directed antibody–drug conjugates (e.g., tisotumab vedotin) are effective for patients whose disease progresses after frontline therapy.
- HER2-targeted therapies (e.g., trastuzumab deruxtecan) may benefit individuals with HER2-overexpressing cervical tumors.
- Immune checkpoint inhibitors (cemiplimab, nivolumab) can be used in PD-L1–positive recurrent disease, although prior treatment with pembrolizumab may affect efficacy.

Conclusion: By combining targeted vaccination, robust screening programs, and multidisciplinary treatment strategies, cervical cancer can be dramatically reduced worldwide. Advanced management incorporates state-of-the-art surgical procedures, chemoradiation, immunotherapies, and emerging targeted therapies to extend survival and enhance quality of life. Ongoing research aims to optimize treatment sequencing, define new biomarkers, and advance global eradication efforts.

Reference:
Tewari KS. Cervical Cancer. New England Journal of Medicine. (2025). Link: https://www.nejm.org/doi/full/10.1056/NEJMra2404457

Guideline: Doxycycline Postexposure Prophylaxis to Reduce Bacterial STI Incidence in High-Risk Populations

19 Dec, 2024 | 22:32h | UTC

Introduction: This summary presents key recommendations from the 2024 Centers for Disease Control and Prevention (CDC) guidelines on using doxycycline postexposure prophylaxis (doxyPEP) to prevent bacterial sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. Targeting men who have sex with men (MSM) and transgender women with at least one bacterial STI in the past 12 months, these guidelines aim to reduce recurrence rates and improve sexual health outcomes through timely prophylactic intervention.

Key Recommendations:

Offer doxyPEP counseling to MSM and transgender women with a recent bacterial STI history, addressing the benefits, harms, and uncertainties of prophylactic doxycycline use.
Advise eligible patients to take a single 200 mg dose of doxycycline as soon as possible (ideally within 72 hours) following condomless oral, anal, or vaginal sexual exposure to reduce their subsequent STI risk.
Reinforce periodic screening (every 3–6 months) for STI markers, including syphilis and HIV serologies, as well as nucleic acid amplification tests for gonorrhea and chlamydia at relevant anatomical sites.
Integrate doxyPEP into comprehensive sexual health services that include risk-reduction counseling, condom use, recommended immunizations, and linkage to HIV preexposure prophylaxis (PrEP) or HIV care, thereby enhancing overall prevention strategies.
Consider extending doxyPEP to other high-risk groups, including heterosexual individuals with recurrent STIs, guided by clinical judgment and shared decision-making.
Monitor and address adverse events, particularly gastrointestinal symptoms, and acknowledge the potential for antimicrobial resistance. Continued vigilance is warranted given the risk of resistance in commensal flora and key STI pathogens, such as Neisseria gonorrhoeae.
Assess social and ethical dimensions of doxyPEP implementation, ensuring equitable access and minimizing potential harms, including stigma or intimate partner violence related to prophylaxis disclosure.

Conclusion: Implementing doxyPEP for MSM and transgender women who have experienced a recent bacterial STI can substantially lower the incidence of recurrent infections. By combining prophylactic doxycycline with routine surveillance, comprehensive preventive services, and careful consideration of resistance patterns, clinicians may enhance patient care and strengthen STI control efforts. Further investigation is needed to establish efficacy in cisgender women, transgender men, nonbinary persons, and other populations at risk. Longer-term, population-based studies focused on antimicrobial resistance and community-level effects will help guide sustainable and equitable use of this prevention strategy.

Reference: Flores J, Davis AM, Hazra A. Doxycycline Postexposure Prophylaxis to Prevent Bacterial Sexually Transmitted Infection. JAMA. Published online December 19, 2024. DOI: http://doi.org/10.1001/jama.2024.24540

Cohort Study: Oral Hormone Therapy and Tibolone Increase Cardiovascular Risk in Menopausal Women

28 Nov, 2024 | 18:42h | UTC

Background: Cardiovascular disease is the leading cause of mortality worldwide, with incidence in women increasing notably during the menopausal transition. Menopausal hormone therapy (MHT) effectively alleviates menopausal symptoms but has been associated with cardiovascular risks in previous studies. The impact of contemporary MHT formulations and administration routes on cardiovascular disease risk in women aged 50–58 remains unclear.

Objective: To assess the effect of different types of contemporary MHT on the risk of cardiovascular disease, focusing on various hormone combinations and administration methods.

Methods: This nationwide register-based emulated target trial included 919,614 Swedish women aged 50–58 years between 2007 and 2020 who had not used MHT in the previous two years. Participants were assigned to one of eight treatment groups—including oral and transdermal therapies—or to a non-initiator group. The primary outcomes were hazard ratios (HRs) for venous thromboembolism (VTE), ischemic heart disease (IHD), cerebral infarction, and myocardial infarction, analyzed separately and as a composite cardiovascular disease outcome.

Results: Among the participants, 77,512 were MHT initiators and 842,102 were non-initiators. During follow-up, 24,089 cardiovascular events occurred. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (HR 1.52, 95% CI 1.11 to 2.08) compared with non-initiators. Initiation of tibolone or oral estrogen-progestin therapy was linked to a higher risk of IHD (HRs 1.46 and 1.21, respectively). A higher risk of VTE was observed with oral continuous estrogen-progestin therapy (HR 1.61), sequential therapy (HR 2.00), and estrogen-only therapy (HR 1.57). Per protocol analyses showed that tibolone use was associated with increased risks of cerebral infarction (HR 1.97) and myocardial infarction (HR 1.94).

Conclusions: Use of oral estrogen-progestin therapy was associated with increased risks of IHD and VTE, while tibolone was linked to higher risks of IHD, cerebral infarction, and myocardial infarction but not VTE. These findings underscore the varying cardiovascular risks associated with different MHT types and administration methods.

Implications for Practice: Clinicians should exercise caution when prescribing oral estrogen-progestin therapy or tibolone for menopausal symptom relief, considering the elevated cardiovascular risks. Alternative MHT options, such as transdermal therapies, may offer a safer profile and should be considered.

Study Strengths and Limitations: Strengths include the large, nationwide cohort and the emulated target trial design, which reduces selection bias and confounding. Limitations involve the lack of data on menopausal status, smoking, and body mass index, which may affect cardiovascular risk. Potential misclassification of exposure and adherence could also impact results.

Future Research: Further studies should investigate the cardiovascular effects of specific progestins within MHT formulations and explore the impact of different doses and durations of therapy.

Reference: Johansson T, Karlsson T, Bliuc D, et al. Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial. BMJ. 2024;387:e078784. DOI: http://doi.org/10.1136/bmj-2023-078784

RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background

28 Nov, 2024 | 12:38h | UTC

Background: Although preexposure prophylaxis (PrEP) effectively reduces HIV transmission, adherence to daily oral regimens is suboptimal among high-risk populations. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, has shown efficacy in cisgender women, but its efficacy in men and gender-diverse individuals remains unclear.

Objective: To evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir compared to background HIV incidence and daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among men and gender-diverse persons.

Methods: In this phase 3, double-blind, randomized trial, 3,271 HIV-negative participants were assigned in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral F/TDF, with matching placebos. Participants were cisgender men, transgender women and men, and gender-nonbinary persons aged 16 or older who have sex with male-assigned partners. The primary endpoint compared HIV incidence in the lenacapavir group to background incidence; secondary analysis compared lenacapavir to F/TDF.

Results: In the modified intention-to-treat analysis (n=3,265), HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). The background HIV incidence was 2.37 per 100 person-years. Lenacapavir significantly reduced HIV incidence compared to background (incidence rate ratio [IRR], 0.04; 95% CI, 0.01–0.18; P<0.001) and F/TDF (IRR, 0.11; 95% CI, 0.02–0.51; P=0.002). No significant safety concerns emerged. Injection-site reactions led to discontinuation in 1.2% of lenacapavir recipients and 0.3% of F/TDF recipients.

Conclusions: Twice-yearly subcutaneous lenacapavir significantly reduced HIV incidence compared to both the background incidence and daily oral F/TDF among men and gender-diverse persons. These findings support lenacapavir as an effective PrEP option in this population.

Implications for Practice: The introduction of a long-acting, twice-yearly injectable PrEP option like lenacapavir could improve adherence and uptake among populations challenged by daily oral regimens.

Study Strengths and Limitations: Strengths include a large, diverse participant population with significant representation of transgender and gender-nonbinary persons, and the use of an active comparator. The novel counterfactual design estimating background HIV incidence avoided ethical issues of placebo controls but may have limitations in accuracy. Limitations include a relatively short follow-up and potential impact of injection-site reactions on adherence. The emergence of resistance mutations in participants who acquired HIV while on lenacapavir is a concern needing further investigation.

Future Research: Further studies should assess the long-term safety, efficacy, and resistance patterns associated with lenacapavir use. Research into optimizing injection techniques to minimize injection-site reactions and exploring lenacapavir’s applicability in other at-risk populations is recommended.

Reference: Kelley CF, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine. Published November 27, 2024. DOI: http://doi.org/10.1056/NEJMoa2411858

RCT: Fezolinetant Reduces Vasomotor Symptoms in Menopausal Individuals Unfit for Hormone Therapy

24 Nov, 2024 | 19:29h | UTC

Background: Vasomotor symptoms (VMS), including hot flushes and night sweats, are prevalent and often debilitating during menopause. Hormone therapy (HT) is effective but contraindicated or unsuitable for many due to medical conditions or personal choice, creating a need for safe, non-hormonal treatments.

Objective: To evaluate the efficacy and safety of fezolinetant, a non-hormonal neurokinin 3 receptor antagonist, in treating moderate to severe VMS in menopausal individuals unsuitable for HT.

Methods: This phase 3b, randomized, double-blind, placebo-controlled trial was conducted across 16 countries. A total of 453 individuals aged 40-65 years with moderate to severe VMS unsuitable for HT were randomized 1:1 to receive fezolinetant 45 mg once daily or placebo for 24 weeks. The primary endpoint was the mean change in daily frequency of moderate to severe VMS from baseline to week 24. Secondary endpoints included changes in VMS severity, sleep disturbance, and safety evaluations.

Results: Of the 452 participants who received at least one dose of the study drug (fezolinetant n=226, placebo n=226), 370 (81.7%) completed the study. The mean age was 54.5 years, and most participants were white (96.7%) and categorized as either HT averse or requiring caution with HT. At week 24, fezolinetant significantly reduced the frequency of VMS compared with placebo (least squares mean difference [LSMD] –1.93 episodes/day; 95% CI –2.64 to –1.22; P<0.001). It also significantly reduced VMS severity (LSMD –0.39; 95% CI –0.57 to –0.21; P<0.001) and improved sleep disturbance scores (LSMD –2.5; 95% CI –3.9 to –1.1; P<0.001). Improvements were observed as early as week 1 and sustained throughout the study. The incidence of treatment-emergent adverse events (TEAEs) was similar between the fezolinetant and placebo groups (65.0% vs. 61.1%, respectively). No significant safety concerns, including liver toxicity, were identified.

Conclusions: Fezolinetant was effective and well-tolerated over 24 weeks in reducing moderate to severe VMS in menopausal individuals unsuitable for HT.

Implications for Practice: Fezolinetant offers a promising alternative for managing VMS in individuals who cannot or choose not to use HT. Clinicians should consider this option but remain cautious due to limited long-term safety data. Individual patient preferences, risk factors, and the novelty of the medication should be weighed in clinical decision-making.

Study Strengths and Limitations: Strengths include the large sample size and extended placebo-controlled duration. Limitations involve the predominantly white study population, potentially limiting generalizability to more diverse groups. The exclusion of individuals over 65 years old and the lack of direct comparison with other non-hormonal treatments also constrain the applicability of the findings.

Future Research: Further studies are needed to assess the long-term safety and efficacy of fezolinetant, particularly in diverse populations and older individuals.

Reference: Schaudig K, et al. Efficacy and safety of fezolinetant for moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy: phase 3b randomised controlled trial. BMJ. 2024; DOI: http://doi.org/10.1136/bmj-2024-079525

Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients

16 Nov, 2024 | 17:29h | UTC

Background: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.

Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.

Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.

Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).

Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.

Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.

Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.

Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.

Reference: Duclos A, Frits ML, Iannaccone C, Lipsitz SR, Cooper Z, Weissman JS, Bates DW. Safety of inpatient care in surgical settings: cohort study. BMJ. 2024; DOI: http://doi.org/10.1136/bmj-2024-080480

Guideline: Management of Urinary Tract Infections in Pediatrics and Adults

5 Nov, 2024 | 18:59h | UTC

Introduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.

Key Recommendations:

Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
  - Nitrofurantoin: 5 days
  - Trimethoprim/sulfamethoxazole: 3 days
  - Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
  - Fluoroquinolones: 5–7 days
  - Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong

Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.

Reference: Nelson Z, Aslan AT, Beahm NP, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Network Open. 2024;7(11). DOI: http://doi.org/10.1001/jamanetworkopen.2024.44495

Cohort Study: Levonorgestrel IUD Use Linked to Increased Breast Cancer Risk in Premenopausal Women

20 Oct, 2024 | 18:13h | UTC

Background: Levonorgestrel-releasing intrauterine systems (LNG-IUSs) are increasingly used, especially among Danish premenopausal women over 30 years old, as a preferred method of hormonal contraception. Previous studies have suggested an increased risk of breast cancer with LNG-IUS use but did not adequately address the duration of continuous use or account for other hormonal contraceptive exposures.

Objective: To assess the risk of breast cancer associated with continuous use of LNG-IUSs, accounting for other hormonal exposures.

Methods: In this nationwide Danish cohort study, 78,595 first-time LNG-IUS users aged 15–49 years from 2000 to 2019 were identified and matched 1:1 by birth year to nonusers of hormonal contraceptives. Exclusion criteria included prior hormonal contraceptive use within 5 years, previous cancer, postmenopausal hormone therapy, and pregnancy at baseline. Participants were followed from initiation until breast cancer diagnosis, other cancer, pregnancy, hormone therapy initiation, emigration, death, or December 31, 2022. Cox proportional hazards models adjusted for confounders estimated hazard ratios (HRs) for breast cancer associated with continuous LNG-IUS use.

Results: During a mean follow-up of 6.8 years, 1,617 breast cancer cases occurred: 720 among LNG-IUS users and 897 among nonusers. The mean age was 38 years. Continuous LNG-IUS use was associated with a higher breast cancer risk compared to nonuse (HR, 1.4; 95% CI, 1.2–1.5). HRs by duration were 1.3 (95% CI, 1.1–1.5) for 0–5 years, 1.4 (95% CI, 1.1–1.7) for >5–10 years, and 1.8 (95% CI, 1.2–2.6) for >10–15 years. Excess breast cancer cases per 10,000 users were 14 (95% CI, 6–23), 29 (95% CI, 9–50), and 71 (95% CI, 15–127), respectively. The trend test for duration was not statistically significant (P = .15).

Conclusions: Continuous use of LNG-IUSs was associated with an increased risk of breast cancer among women aged 15–49 years compared to nonuse of hormonal contraceptives. The absolute increase in risk was low.

Implications for Practice: Healthcare providers should inform women about the potential increased breast cancer risk associated with LNG-IUS use, especially considering its widespread and long-term use among premenopausal women. While the absolute risk increase is small, this information is essential for making informed contraceptive choices.

Study Strengths and Limitations: Strengths include the large, nationwide cohort and adjustment for multiple confounders. Limitations include potential underestimation of risk due to unrecorded LNG-IUS removals before the recommended duration, lack of a statistically significant trend with duration suggesting possible low statistical precision or non-causal association, and the possibility of unmeasured confounding.

Future Research: Further studies are needed to confirm these findings, clarify the causal relationship, and understand the mechanisms underlying the potential increased breast cancer risk with LNG-IUS use.

Reference: Mørch LS, Meaidi A, Corn G, et al. Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems. JAMA. Published online October 16, 2024. DOI: http://doi.org/10.1001/jama.2024.18575

Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants

19 Sep, 2024 | 21:12h | UTC

Direct oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.

Elective Surgical or Nonsurgical Procedures

Classify Bleeding Risk of Procedures:

Minimal Risk:
- Minor dental procedures (e.g., cleaning, extractions)
- Minor dermatologic procedures (e.g., skin lesion removal)
- Cataract surgery
Low to Moderate Risk:
- Endoscopic procedures without high-risk interventions
- Cholecystectomy
- Inguinal hernia repair
High Risk:
- Major surgery (e.g., cancer surgery, joint replacement)
- Procedures involving neuraxial anesthesia
- Endoscopic procedures with high-risk interventions (e.g., large polyp removal)

DOAC Management Strategies:

Minimal Bleeding Risk Procedures:
- Option 1: Continue DOACs without interruption.
- Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
Low to Moderate Bleeding Risk Procedures:
- Preoperative:
  - Discontinue DOACs 1 day before the procedure.
  - This allows approximately 2 half-lives for drug clearance.
- Postoperative:
  - Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
High Bleeding Risk Procedures:
- Preoperative:
  - Discontinue DOACs 2 days before the procedure.
  - This allows approximately 4-5 half-lives for drug clearance.
- Postoperative:
  - Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.

Evidence Supporting These Strategies:

The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
- Thromboembolism: 0.2%–0.4%
- Major Bleeding: 1%–2%

Postoperative DOAC Resumption:

Assess surgical-site hemostasis before resuming DOACs.
Delay resumption if there is ongoing bleeding or concerns about hemostasis.
For high bleeding risk procedures, consider a longer delay (2–3 days).

Perioperative Heparin Bridging:

Not recommended for patients on DOACs.
Bridging increases bleeding risk without reducing thromboembolism.
DOACs have rapid offset and onset, making bridging unnecessary.

Special Considerations

Patients with Impaired Renal Function:

For CrCl 30–50 mL/min:
- Dabigatran: Extend preoperative discontinuation by an additional day.
For CrCl <30 mL/min:
- Dabigatran is contraindicated.
- For other DOACs, consider extending discontinuation to 3–4 days before surgery.

Patients Undergoing Neuraxial Anesthesia:

Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
Minimizes risk of spinal or epidural hematoma.

Dental Procedures:

Generally safe to continue DOACs.
For added safety:
- Omit or delay the dose on the day of the procedure.
- Employ local hemostatic measures (e.g., tranexamic acid mouthwash).

Endoscopic Procedures:

Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
- Follow standard DOAC interruption for low to moderate bleeding risk.
High-risk procedures (e.g., polypectomy of large polyps):
- Extend DOAC discontinuation by an additional day pre- and post-procedure.

Patients Unable to Resume Oral Medications Postoperatively:

Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
Avoid therapeutic-dose LMWH due to bleeding risk.

Emergent, Urgent, or Semiurgent Procedures

Risks:

Higher bleeding risk: Up to 23%
Thromboembolism risk: Up to 11%

Management Strategies:

Assess Time Since Last DOAC Dose:
- If within 48 hours, consider that significant anticoagulant effect may persist.
Laboratory Testing (if available):
- DOAC Level Testing:
  - ≥50 ng/mL: Consider using reversal agents.
  - <50 ng/mL: May proceed without reversal agents.
Use of Reversal Agents:
- For Dabigatran:
  - Idarucizumab (5 g IV)
- For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
  - Andexanet alfa (dosing based on last dose timing and amount)
  - Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
Proceeding Without Testing:
- If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
- If >48 hours since last dose, may proceed without reversal.

Considerations:

Reversal agents are expensive and may carry thrombotic risks.
Use should be judicious, weighing risks and benefits.
Consult hematology or thrombosis experts when possible.

Key Takeaways

Elective Procedures:
- Utilize standardized protocols based on procedural bleeding risk.
- Routine preoperative DOAC level testing is unnecessary.
- Avoid heparin bridging.
Emergent/Urgent Procedures:
- Reversal agents may be appropriate when significant DOAC levels are present.
- Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
Patient Communication:
- Ensure patients understand the plan for DOAC interruption and resumption.
- Provide clear instructions regarding timing and dosing.
Interdisciplinary Coordination:
- Collaborate with surgical teams, anesthesiologists, and pharmacists.
- Use electronic medical records and clinical decision support tools to enhance communication.

Conclusion

By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.

Reference: Douketis JD, Spyropoulos AC. Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review. JAMA. 2024;332(10):825–834. doi:10.1001/jama.2024.12708

CDC Updates Contraceptive Guidelines for 2024 – Centers for Disease Control and Prevention

18 Aug, 2024 | 13:51h | UTC

Introduction: The Centers for Disease Control and Prevention (CDC) has released updated recommendations in the “U.S. Selected Practice Recommendations for Contraceptive Use, 2024” and “U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.” These guidelines provide healthcare providers with the latest evidence-based recommendations to support patient-centered contraceptive care, aiming to remove unnecessary barriers and ensure equitable access to contraception.

Key Points:

1 – Intrauterine Device (IUD) Placement:

– Routine use of misoprostol is not recommended for IUD placement, except in selected cases. Lidocaine (topical or paracervical block) is newly recommended to reduce patient pain during IUD placement.

2 – Bleeding Irregularities with Implants:

– Hormonal treatments and antifibrinolytic agents may improve bleeding irregularities associated with implant use, although bleeding often recurs after stopping treatment. NSAIDs and selective estrogen-receptor modulators may also be effective, with benefits persisting post-treatment.

3 – Testosterone Use and Pregnancy Risk:

– Testosterone therapy may not prevent pregnancy in transgender, gender-diverse, and nonbinary individuals with a uterus. Contraceptive counseling and services should be offered to those at risk of pregnancy who do not desire it.

4 – Self-Administration of Injectable Contraceptives:

– Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) should be available for self-administration, providing an additional option for those seeking injectable contraception.

5 – Updates in Medical Eligibility Criteria:

– The 2024 guidelines include revised recommendations for patients with chronic kidney disease, updates for those who are breastfeeding, postpartum, or post-abortion, and considerations for individuals with obesity, cardiovascular conditions, and other comorbidities.

6 – Patient-Centered Counseling:

– The guidelines emphasize the importance of providing contraceptive care in a noncoercive manner, supporting the individual’s values, goals, and reproductive autonomy. Healthcare providers are encouraged to recognize and address structural inequities and avoid discrimination in contraceptive counseling.

Conclusion: These updated guidelines from the CDC are designed to support healthcare providers in delivering equitable, patient-centered contraceptive care. By removing unnecessary barriers and providing clear guidance on managing complex contraceptive issues, the recommendations aim to improve access to contraception and support informed, autonomous decision-making among patients.

Guideline Reference: Curtis, K. M., Nguyen, A. T., Tepper, N. K., et al. (2024). U.S. Selected Practice Recommendations for Contraceptive Use, 2024. MMWR Recommendations and Reports, 73(3).

Meta-analysis: SSRIs Significantly Reduce Symptoms but Increase Adverse Events in Premenstrual Syndrome – Cochrane Database Syst Rev

17 Aug, 2024 | 16:04h | UTC

Study Design and Population: This systematic review and meta-analysis included 34 randomized controlled trials (RCTs) involving 4,563 women diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). The studies primarily focused on evaluating the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) compared to placebo. The trials involved a diverse population, predominantly from Western countries, with participants aged between 18 and 49 years.

Main Findings: SSRIs likely reduce overall self-rated premenstrual symptoms in women with PMS and PMDD, with a standardized mean difference (SMD) of -0.57 (95% CI: -0.72 to -0.42). Continuous SSRI administration was more effective than luteal phase administration (SMD -0.69 vs. -0.39). However, SSRIs were associated with a higher risk of adverse events, including nausea (OR 3.30), insomnia (OR 1.99), sexual dysfunction (OR 2.32), and fatigue (OR 1.52).

Implications for Practice: SSRIs are an effective treatment option for reducing premenstrual symptoms in women with PMS and PMDD, particularly when administered continuously. However, the increased risk of adverse events must be carefully considered, and patients should be monitored closely. Further research is necessary to confirm these findings and explore long-term safety.

Reference: Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB. (2024). Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews, 2024(8), CD001396. DOI: 10.1002/14651858.CD001396.pub4.

AAN updated practice guidelines for epilepsy and pregnancy – Neurology

27 May, 2024 | 20:23h | UTC

Introduction:

The American Academy of Neurology (AAN), the American Epilepsy Society (AES), and the Society for Maternal-Fetal Medicine (SMFM) have published a comprehensive guideline focusing on the management of epilepsy in individuals of childbearing potential. This guideline addresses the use of antiseizure medications (ASMs) and the impact of folic acid supplementation on major congenital malformations (MCMs), perinatal outcomes, and neurodevelopmental outcomes.

Key Points:

Optimizing ASM Therapy Preconceptionally: Clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, ideally starting this process preconceptionally.
Minimizing Convulsive Seizures During Pregnancy: It is crucial to minimize convulsive seizures in pregnant individuals to reduce risks to both the parent and the fetus.
Monitoring and Adjusting ASM Levels: ASM levels should be monitored throughout pregnancy, and doses should be adjusted based on serum levels and seizure control.
Preferred ASMs for Pregnancy: Lamotrigine, levetiracetam, and oxcarbazepine are recommended when appropriate, as they are associated with lower risks of MCMs compared to other ASMs.
Avoiding Certain ASMs: Valproic acid should be avoided to minimize risks of MCMs, neural tube defects, and poor neurodevelopmental outcomes. Topiramate should also be avoided due to risks of offspring being born small for gestational age.
Folic Acid Supplementation: At least 0.4 mg of folic acid should be prescribed daily preconceptionally and during pregnancy to decrease the risk of neural tube defects and possibly improve neurodevelopmental outcomes.
Counseling on Risks and Monitoring: Clinicians must counsel patients on the potential risks associated with different ASMs and ensure regular fetal screenings to detect congenital malformations early.

Conclusion:

These guidelines provide essential, evidence-based recommendations for managing epilepsy in individuals of childbearing potential, emphasizing the importance of preconception planning, careful medication selection, and ongoing monitoring to optimize both maternal and fetal health outcomes.

Guideline Reference (link to free full-text):

Pack, A.M., et al. (2024). Practice Guideline From the AAN, AES, and SMFM: Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication. Neurology, 102, e209279. Available at: https://doi.org/10.1212/WNL.0000000000209279.

Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open

25 May, 2024 | 19:55h | UTC

This randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.

Reference (link to free full-text):

Grzegorz Raba et al. (2024). Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis A Randomized Clinical Trial. JAMA Netw Open, 7(5), e248661. DOI: 10.1001/jamanetworkopen.2024.8661

Review: Key findings from the Women’s Health Initiative studies on postmenopausal interventions – JAMA

3 May, 2024 | 13:34h | UTC

The Women’s Health Initiative (WHI) studied the impact of various interventions on postmenopausal women aged 50-79, using data from 161,808 participants between 1993 and 2018. The findings suggest that hormone therapy, specifically with conjugated equine estrogens and medroxyprogesterone acetate, does not reduce the risk of cardiovascular diseases, dementia, or other chronic conditions in postmenopausal women. It is, however, effective for managing severe menopausal symptoms when initiated before age 60 in women without contraindications. The trials also concluded that universal supplementation of calcium and vitamin D does not effectively prevent fractures and should be limited to those not meeting dietary intake recommendations. Furthermore, a low-fat diet rich in fruits, vegetables, and grains did not reduce the incidence of breast or colorectal cancer, though it may decrease breast cancer mortality rates, indicating the need for further investigation.

Reference (link to free full-text for a limited period):

Manson JE et al. (2024). The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA, Published online May 1, 2024. DOI: 10.1001/jama.2024.6542.

USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality

1 May, 2024 | 21:45h | UTC

Study Design and Population:

The US Preventive Services Task Force (USPSTF) performed a systematic review and collaborated on modeling studies to evaluate the effectiveness of various mammography-based breast cancer screening strategies. This assessment included factors such as age of initiation and cessation of screening, screening intervals, modalities, and the use of supplemental imaging. The population studied consisted of cisgender women and all other persons assigned female at birth who are 40 years or older and at average risk of breast cancer.

Main Findings:

The USPSTF concludes with moderate certainty that biennial screening mammography for women aged 40 to 74 years provides a moderate net benefit in reducing the incidence of and progression to advanced breast cancer, as well as in decreasing breast cancer morbidity and mortality. However, the evidence is insufficient to assess the benefits and harms of mammography screening in women aged 75 and older, as well as the use of supplemental screening with ultrasound or MRI in women with dense breasts.

Implications for Practice:

Based on these findings, the USPSTF recommends biennial screening mammography for women aged 40 to 74 years. This recommendation aims to optimize breast cancer outcomes while considering the balance of benefits and harms of screening. There is a need for further research to clarify the benefits and risks associated with mammography in women older than 75 and for those with dense breasts considering supplemental screening.

Commentary on X (thread – click for more)

🧵 Just published: USPSTF recommends all women undergo routine #breastcancer screening every other year beginning at age 40, an update from the 2016 recommendation to start at age 50.
https://t.co/xDPK4qu7JH pic.twitter.com/3zVBMWeuKb

— JAMA (@JAMA_current) April 30, 2024

Reference (link to free full-text):

Screening for Breast Cancer US Preventive Services Task Force Recommendation Statement. JAMA. Published online April 30, 2024. doi:10.1001/jama.2024.5534

RCT: Radiation therapy alone superior to chemoradiation in low-grade localized endometrial cancer recurrences

1 May, 2024 | 21:41h | UTC

This randomized clinical trial assessed the effectiveness of radiation therapy alone versus concurrent chemoradiation in treating localized recurrences of endometrial cancer. Conducted from February 2008 to August 2020, the study involved 165 patients who were randomized to receive either radiation therapy alone or chemoradiation with weekly cisplatin. Findings indicate that radiation therapy alone resulted in longer progression-free survival (PFS) compared to chemoradiation, with a median PFS not reached for radiation alone versus 73 months for chemoradiation. Additionally, radiation therapy demonstrated lower rates of acute toxicity. The study concluded that for patients with low-grade and primarily vaginal recurrences, radiation therapy alone is the preferable treatment option, offering excellent outcomes without the added toxicity of chemotherapy.

Reference (link to abstract – $ for full-text):

Ann H. Klopp et al. (Year). Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial. Journal of Clinical Oncology. DOI: 10.1200/JCO.23.01279

RCT: Aspirin fails to improve invasive disease-free survival in breast cancer patients

1 May, 2024 | 21:37h | UTC

This randomized clinical trial assessed the efficacy of daily aspirin (300 mg) as adjuvant therapy in reducing breast cancer recurrence among 3020 participants with high-risk nonmetastatic breast cancer across the United States and Canada. The study, which followed participants for a median of 33.8 months, found no significant benefit of aspirin on invasive disease-free survival or overall survival, with the hazard ratio for disease-free survival being 1.27 (95% CI, 0.99-1.63; P = .06) and for overall survival 1.19 (95% CI, 0.82-1.72). Given these findings, aspirin is not recommended as an adjuvant treatment for breast cancer, challenging earlier observational data that suggested a potential survival benefit in breast cancer survivors. The trial was concluded early due to the lack of observed benefits, with adverse event rates being similar in both the aspirin and placebo groups.

Commentary on X:

Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. https://t.co/uPWTeaqXdJ pic.twitter.com/x6Qb4bRlqF

— JAMA (@JAMA_current) April 29, 2024

Reference (link to abstract – $ for full-text):

Wendy Y. Chen et al. (2024). Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial. JAMA, Published online April 29, 2024. doi:10.1001/jama.2024.4840

Observational Study: Synergistic effects of early menopause and vascular risk on cognitive decline in postmenopausal women

27 Apr, 2024 | 18:20h | UTC

Study Design and Population:
This study analyzed data from 8,360 postmenopausal women and an equal number of age-matched male participants from the Canadian Longitudinal Study on Aging. Researchers assessed the independent and combined effects of age at menopause, vascular risk factors, and history of hormone therapy on cognitive outcomes. Participants’ cognitive function was measured using a global cognitive composite at baseline and again at a 3-year follow-up.

Main Findings:
The study found a synergistic interaction between early menopause (ages 35-48) and high vascular risk, significantly associated with lower cognitive scores at follow-up. Specifically, earlier menopause combined with higher vascular risk resulted in greater cognitive decline, compared to their individual effects. Notably, hormone therapy did not modify this association. This pattern was not observed in female participants with average or later menopause ages, nor in the age-matched male cohort.

Implications for Practice:
The findings underscore the importance of considering both endocrine and vascular health as predictive markers in dementia prevention strategies, particularly for women. These results suggest that women with early menopause and vascular risk factors should be closely monitored to mitigate their higher risk of cognitive impairment.

Reference (link to abstract – $ for full-text):

Alexander, M.W. et al. (2024). Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging. Neurology, 102(9), 1-12. DOI: https://doi.org/10.1212/WNL.0000000000209298.