What non-hormonal options are available for a patient with severe vaginal dryness, recurrent urinary tract infections (UTIs), hot flashes, and brain fog, who has tried sublingual hormonal replacement therapy (HRT) and developed thrombosis of leg vessels?

Non-Hormonal Management Options for Menopausal Symptoms with History of Thrombosis

Given this patient's history of venous thrombosis on systemic hormone therapy, systemic hormonal replacement is absolutely contraindicated, but she has excellent non-hormonal options for each of her symptoms: vaginal moisturizers and lubricants for vaginal dryness/recurrent UTIs, SNRIs or gabapentin for hot flashes, and addressing sleep disruption from hot flashes for brain fog. 1

Vaginal Dryness and Recurrent UTIs

First-Line Non-Hormonal Treatment

• Water-based or silicone-based vaginal moisturizers should be used regularly (3-5 times weekly) as the primary treatment for vaginal dryness. 1 Silicone-based products last longer than water-based or glycerin-based formulations. 1

• Water-based lubricants should be used specifically for sexual activity to address dyspareunia and improve sexual function. 1

• Choose products that are optimally balanced in terms of osmolality and pH, physiologically similar to natural vaginal secretions. 2, 3 Products with potentially harmful ingredients or unphysiological pH should be avoided. 3

Recurrent UTI Prevention

• Vaginal estrogen therapy (local only) should be strongly considered despite her thrombosis history, as it has minimal systemic absorption and carries very low systemic risks. 4 The European Association of Urology gives a STRONG recommendation for vaginal estrogen to prevent recurrent UTI in postmenopausal women. 4

• Women already on systemic estrogen can safely add vaginal estrogen, and conversely, women with contraindications to systemic estrogen can safely use vaginal estrogen alone. 4 Large prospective cohort studies of over 45,000 women using topical estrogen showed no concerning safety signals regarding stroke, venous thromboembolism, invasive breast cancer, colorectal cancer, or endometrial cancer. 4

• Vaginal estrogen works by reducing vaginal atrophy, restoring the vaginal microbiome with protective Lactobacillus species, normalizing pH, and decreasing UTI frequency through mechanisms that systemic estrogen cannot achieve. 4

• Common formulations include estradiol vaginal tablets, estradiol vaginal rings, or estrogen-based vaginal creams. 1, 4

Additional Interventions

• Pelvic floor physical therapy should be considered if there are signs of pelvic floor dysfunction contributing to urogenital symptoms. 1, 4

• Vaginal dilators may be helpful for vaginal stenosis or scarring, though evidence is limited. 1

Hot Flashes

First-Line Pharmacologic Options

• SNRIs (specifically venlafaxine) are recommended as first-line treatment, starting at 37.5 mg/day and increasing to 75 mg/day as tolerated. 1 This is effective for reducing both frequency and severity of hot flashes. 5

• Gabapentin is an equally effective first-line option, starting at 300 mg/day and increasing to 900 mg/day as tolerated, which reduces hot flash severity by 46% at 8 weeks. 1, 5

• SSRIs are also recommended as an alternative pharmacologic option for vasomotor symptoms. 1

Non-Pharmacologic Interventions

• Lifestyle modifications including weight loss if overweight or obese, exercise/physical activity, and environmental modifications (keeping rooms cool, layered clothing). 1

• Acupuncture has shown effectiveness in controlling hot flashes in small studies. 1

• Cognitive behavioral therapy (CBT) and hypnosis may reduce the perceived burden of hot flashes. 1

• Yoga and other mind-body interventions can be tried. 1

What to Avoid

• Phytoestrogens, botanicals, and dietary supplements have very limited data on effectiveness and safety, and should be considered category 2B options only. 1

• Custom compounded bioidentical hormones are not recommended as data supporting claims that they are safer and more effective than standard hormones are lacking. 1

Brain Fog

Addressing the Root Cause

• Brain fog in this context is most likely secondary to sleep disturbance from hot flashes rather than a primary cognitive disorder. 5 Two weeks of symptoms is insufficient to diagnose neurodegenerative disease. 5

• Treating the hot flashes aggressively with SNRIs or gabapentin should improve the cognitive symptoms by restoring normal sleep architecture. 5

If Symptoms Persist

• Consider functional causes including depression, anxiety, or stress-related cognitive symptoms. 5

• Arrange longitudinal follow-up with repeat cognitive assessment in 3-6 months to document any progressive decline if symptoms persist despite treatment of hot flashes. 5

• Refer for comprehensive neuropsychological testing only if objective cognitive impairment is documented or symptoms persist despite adequate treatment. 5

Psychosocial Support

• Referral for psychoeducational support, group therapy, sexual counseling, or marital counseling should be offered to address anxiety, stress, sexual comfort, and mood changes associated with these symptoms. 1

Critical Pitfall to Avoid

Do not use systemic hormone therapy in any form (oral, transdermal, sublingual) given her documented history of thrombosis. 1 Systemic hormone therapy is absolutely contraindicated with a history of thromboembolic event. 1 However, this does NOT preclude the use of local vaginal estrogen, which has minimal systemic absorption and excellent safety data. 4