What are the recommended management strategies for a perimenopausal woman, including lifestyle modifications, hormone therapy, non‑hormonal options, treatment of genitourinary symptoms, osteoporosis screening, and follow‑up?

Perimenopausal Management

Lifestyle Modifications as Foundation

All perimenopausal women should engage in regular weight-bearing and resistance exercise, maintain calcium intake of 1,200 mg daily and vitamin D3 600-1,000 IU daily, avoid tobacco, and limit alcohol consumption. 1

• Physical activity and weight-bearing exercise form the cornerstone of bone health maintenance during perimenopause, with evidence showing improved bone mineral density when combined with adequate supplementation 1, 2
• Smoking cessation and alcohol limitation (no more than moderate intake) reduce osteoporosis risk and improve overall health outcomes 1
• Environmental modifications for vasomotor symptoms include maintaining cool room temperatures and dressing in layers 1

Vasomotor Symptom Management

For hot flashes and night sweats, first-line pharmacologic treatment consists of SNRIs (venlafaxine) or gabapentin, as these are safe and effective non-hormonal options. 1

• Venlafaxine has proven efficacy in reducing hot flush intensity and severity 1
• Gabapentin (anticonvulsant) effectively reduces vasomotor symptoms 1
• Avoid SSRIs that inhibit CYP2D6 (particularly paroxetine) if the patient may require tamoxifen in the future, as these may reduce tamoxifen's conversion to active metabolites 1
• Acupuncture has demonstrated benefit in meta-analyses for reducing menopausal symptoms and hot flashes 1
• Lifestyle interventions including rhythmic breathing, avoiding spicy foods, caffeine, and alcohol provide variable but potentially helpful results 1

Genitourinary Symptom Management

Low-dose intravaginal estrogens are the preferred treatment for vulvovaginal dryness, dyspareunia, and urinary symptoms (urgency, dysuria, recurrent UTIs). 1

• Silicone-based vaginal lubricants and moisturizers last longer than water-based or glycerin-based products for immediate symptom relief 1
• Low-dose estrogen vaginal tablets or estradiol vaginal rings may be used for urogenital atrophy, with treatment duration of at least 12 weeks 1
• Vaginal dilators or pelvic floor relaxation techniques help manage dyspareunia secondary to vaginal stenosis 1
• Combination of non-hormonal and hormonal therapies often provides optimal symptom control 1

Osteoporosis Screening Strategy

Begin osteoporosis screening at age 60 for women at increased risk, or earlier (age 60-64) if body weight <70 kg or other significant risk factors are present. 1

• Bone mineral density measurement via DEXA scan at the femoral neck is the gold standard for fracture risk prediction 1
• Lower body weight (<70 kg) is the single best predictor of low bone mineral density in this age group 1
• Additional risk factors warranting earlier screening include: family history of fracture, smoking, weight loss, decreased physical activity, low calcium/vitamin D intake 1
• African-American women have higher average bone density than white women and are less likely to benefit from routine screening 1
• Repeat DEXA scanning should occur at minimum 2-year intervals, though longer intervals may be adequate for screening 1

Bone Health Pharmacologic Management

If osteoporosis is diagnosed (T-score ≤-2.5) or osteopenia with risk factors (T-score ≤-2.0 with additional risk factors), initiate bisphosphonate therapy as first-line treatment. 3, 4

• Alendronate 70 mg once weekly or risedronate 35 mg once weekly are preferred first-line bisphosphonates, reducing hip fractures by 50% and vertebral fractures by 47-56% 3, 4
• Zoledronic acid 5 mg IV annually is an alternative for patients unable to tolerate oral bisphosphonates 3
• Calcium 1,200 mg daily and vitamin D 800 IU daily are mandatory concurrent supplements, as pharmacologic therapy is significantly less effective without adequate supplementation 3, 4
• Initial treatment duration is 5 years, after which fracture risk should be reassessed 3, 4
• Do not monitor bone density during the initial 5-year treatment period, as this provides no clinical benefit 3, 4
• Denosumab 60 mg subcutaneously every 6 months is second-line for patients with bisphosphonate contraindications or intolerance 4

Hormone Replacement Therapy Considerations

Systemic HRT is generally not recommended as first-line osteoporosis prevention in perimenopause, though it may be considered for women with significant vasomotor symptoms who also have bone health concerns. 5, 6

• HRT prevents bone loss and reduces fracture risk at all sites by 20-40%, with efficacy regardless of baseline fracture risk 5
• HRT is considered second-line for osteoporosis prevention in most women, though it has a role in perimenopausal women with menopausal symptoms who are at fracture risk 6
• The benefit-risk balance depends on individual risk profile, type of estrogen/progestogen, dose, and route of administration 5
• For early postmenopausal women at low-moderate fracture risk over 10 years but higher lifetime risk, HRT may be considered as first option for bone health maintenance when specific bone-active medications are not yet warranted 5
• Subsequent reassessment of benefit-risk balance is recommended, with possible switching to other osteoporosis treatments if balance becomes unfavorable 5

Follow-Up and Monitoring

Assess vasomotor symptoms, genitourinary symptoms, and bone health risk factors at each clinical encounter. 1

• Regular clinical assessment should include inquiry about hot flashes, night sweats, vaginal dryness, dyspareunia, and urinary symptoms 1
• Monitor adherence to calcium and vitamin D supplementation 1
• Evaluate exercise patterns and weight-bearing activity 1
• Screen for new fracture risk factors including smoking status, alcohol use, weight changes 1

Critical Pitfalls to Avoid

• Never use SERMs (raloxifene, tamoxifen) for osteoporosis prevention in premenopausal women, as raloxifene actually decreases bone density in this population 7
• Do not prescribe systemic HRT to women with history of breast cancer for osteoporosis management; use bisphosphonates instead 1
• Avoid hormonal vaginal therapies in women taking aromatase inhibitors due to variable estrogen absorption 1
• Do not screen for CYP2D6 enzyme status when prescribing SSRIs/SNRIs for vasomotor symptoms 1