Expanding Horizons: Rethinking Menopausal Hormone Therapy Guidelines for Inclusive Care

Abstract

The current guidelines on MHT state that initiation within 10 years of menopause or before age 60, according to data from the Women's Health Initiative (WHI) studies, should be made. These guidelines try to balance risks and benefits; however, it has the side effect of not allowing women in those parameters. Most of them experience severe symptoms during menopause or have higher risks of bone loss and fractures. We critically review the evidence that these guidelines are based on and discuss subsequent work critiquing the rigid inclusion criteria. We propose an expansion of MHT initiation to meet the most diverse needs, and therefore enhance the quality of life and preventive care in postmenopausal women.

Introduction

MHT remains a cornerstone of management both for the alleviation of menopausal symptoms and the prevention of bone loss. However, guidelines promulgated by the Women's Health Initiative have restricted initiation of MHT to within 10 years of menopause or less than 60 years of age. Although these criteria, based on the evidence provided in risk assessments, provide apparent protection, they inadvertently restrict therapy to women outside these narrow boundaries who are best suited to receive it.

This article assesses the backgrounds and justifications for current guidelines on MHT, critically analyses their limitations, and discusses emergent evidence favoring a broader approach. This call for an expansive view hopefully identifies unmet needs in care at menopause and provides guidance on the direction for future evolution in hormone therapy guidelines.

Historical Context of MHT Guidelines

Findings from the WHI Studies

The WHI trials, initiated in the 1990s, were pivotal in shaping MHT guidelines. These large-scale studies sought to evaluate the long-term effects of hormone therapy on chronic disease prevention. Key outcomes included:

• Increased Risk of Cardiovascular Events: Older women initiating MHT were found to have an elevated risk of thromboembolism and stroke. The timing of therapy initiation appeared critical, with earlier use showing more favorable cardiovascular profiles.

• Breast Cancer Risk: Combination estrogen-progestin therapy was associated with a small but significant increase in breast cancer incidence, though this risk varied with duration and type of hormone therapy.

• Benefits for Bone Health: MHT demonstrated substantial protective effects against osteoporosis and fractures, particularly in postmenopausal women at high risk for bone loss.

Translating WHI Findings into Guidelines

Based on these findings, guidelines emphasized the "timing hypothesis," which posits that the benefits of MHT outweigh the risks when initiated closer to menopause. This led to the recommendation to restrict MHT initiation to within 10 years post-menopause or under the age of 60. While well-intentioned, these criteria have proven overly rigid, excluding many women who could benefit from therapy.

Limitations of Current Guidelines

Exclusion of Symptomatic Women Outside the Criteria

Some symptoms persist, including hot flashes, night sweats, and genitourinary syndrome of menopause, well past the time of the initial postmenopausal phase. Women having symptoms persisting beyond 10 years are generally excluded from MHT therapy and are left with limited and poor quality of care for their symptoms.

Missed Opportunities for Bone Health Protection

Osteoporosis is a serious health issue for aging women: fractures cause severe morbidity and mortality. Current guidelines don't meet the needs of elderly women at high fracture risk, despite well-established evidence from numerous studies documenting MHT efficacy in preventing bone loss and diminishing fracture incidence regardless of age group.

Individual Variability in Risk

Chronological age and time elapsed since menopause cannot explain variations in health status at the individual level. Other crucial factors include heart health, past family history of breast cancer, and lifestyle for the safety and efficacy of MHT, hinting at greater personalization requirements.

Underrepresentation in Clinical Trials

The WHI primarily consisted of older postmenopausal women with pre-existing cardiovascular risks, thus limiting the generalizability of findings to younger, healthier populations or those with different risk profiles. This has contributed to overly cautious interpretations of MHT's safety in broader populations.

Reassessing the Evidence

Cardiovascular Outcomes and the Timing Hypothesis

Recent studies have reinforced the timing hypothesis while providing greater nuance:

• Early Initiation: When initiated within 10 years of menopause, MHT shows neutral or even protective cardiovascular effects, likely due to improved endothelial function and lipid profiles.

• Later Initiation: While risks increase with age and time since menopause, absolute risks remain modest in many cases, particularly with transdermal or low-dose formulations.

Breast Cancer Risk Revisited

Meta-analyses and long-term studies have clarified breast cancer risks associated with MHT:

• Duration of Use: Short-term MHT (<5 years) carries minimal risk, particularly when used for symptom relief.

• Type of Therapy: Estrogen-only therapy, often prescribed to hysterectomized women, is associated with lower breast cancer risk compared to combination estrogen-progestin therapy.

Bone Health Benefits Across Age Groups

MHT consistently demonstrates benefits for bone health, reducing the risk of vertebral and hip fractures. Evidence suggests that these benefits extend to older women, challenging the exclusion of this population from therapy consideration.

Expanding the Guidelines: A Proposed Framework

Individualized Risk Assessment

Future guidelines should prioritize personalized care by:

• Incorporating comprehensive risk assessments, including cardiovascular health, breast cancer history, and bone density.

• Utilizing tools such as the FRAX (Fracture Risk Assessment Tool) and ASCVD (Atherosclerotic Cardiovascular Disease) risk calculators to guide decision-making.

Expanding Age and Time Limits

Guidelines must recognize that age and time since menopause are not absolute contraindications. Key recommendations include:

• Allowing MHT initiation in symptomatic women or those at high fracture risk, irrespective of age, with appropriate risk mitigation strategies.

• Supporting individualized decision-making based on a holistic assessment of risks and benefits.

Tailored Therapeutic Approaches

• Low-Dose and Local Therapies: For women with GSM or mild symptoms, vaginal estrogen or low-dose systemic therapy can provide relief with minimal systemic risk.

• Alternative Delivery Methods: Transdermal patches, gels, and sprays reduce thrombotic risks compared to oral formulations and offer greater flexibility in dosing.

Addressing Psychological and Emotional Well-being

Untreated menopausal symptoms often lead to psychological distress, including anxiety, depression, and diminished quality of life. Expanding access to MHT addresses these issues, fostering emotional well-being alongside physical health.

Addressing Barriers to Implementation

Education and Awareness

• Empower clinicians with updated evidence and practical tools to assess MHT candidacy.

• Debunk misconceptions stemming from outdated interpretations of WHI findings.

Shared Decision-Making

• Engage patients in open discussions about the risks and benefits of MHT tailored to their individual needs and preferences.

• Emphasize the role of patient autonomy in therapeutic decision-making.

Monitoring and Follow-Up

• Implement regular follow-up protocols to reassess risks, monitor symptom relief, and adjust therapy as needed.

• Leverage digital health tools to track therapy outcomes and enhance patient engagement.

Implications for Future Research

Long-Term Outcomes of Expanded MHT Use

Future studies should be conducted into the safety and efficacy of MHT in women initiating therapy later in life or beyond traditional criteria, such as cardiovascular outcomes, risks of cancer, and fracture prevention.

Alternative Therapies and Combinations

Further research should involve novel hormonal formulations, select estrogen receptor modulators (SERMs), and combination therapies that might prove safer and more effective for larger groups of patients. Non-hormonal alternatives also should be developed and validated.

Inclusivity in Clinical Trials

Diverse populations in clinical trials must be included so that findings can be applicable across a spectrum of ages, ethnicities, and health statuses. Including underrepresented groups will give insight into population-specific risks and benefits and thus help to promote equitable care.

Conclusion

The restrictive criteria in initiating MHT based on findings from the WHI have served to leave the majority of women underserved. A shift towards a more inclusive approach to individualized care can help answer unmet needs and improve the quality of life among postmenopausal women. It is perfectly feasible and should be done with evolving evidence reflected in guidelines toward advancing menopausal care. This change will ensure that MHT becomes a viable option for all women who can benefit, irrespective of age or time since menopause, thus fostering equity and improving health outcomes across diverse populations.

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