A Functional Medicine Perimenopausal Protocol: Specialty Testing, Therapeutic Nutrition, and Supplements

Perimenopause is a normal part of the female aging process leading into the menopausal phase of life. While it is normal, the symptoms experienced can feel anything but – irregular periods, changes in mood, hot flashes, and sleep disturbances can contribute to feelings of despair and unknown. 

As many as 90% of women seek medical help for managing menopausal symptoms. Fortunately, a smooth transition is possible with an integrative treatment plan that supports the body in adjusting to the menopausal stage of life.

[signup]

What Is Perimenopause?

Perimenopause, meaning "around menopause," encompasses the final years of a woman's fertility. This menopausal transition is characterized by the natural decline in reproductive hormones as ovarian function diminishes.

There are two stages to perimenopause: the early and late transitions. Perimenopause begins with the onset of menstrual irregularity. During the early transition, menstrual cycles are relatively regular, varying between 21 and 35 days. The late transition is characterized by prolonged amenorrhea, with the absence of a menstrual period for at least 60 days. The end of perimenopause is marked by twelve consecutive months without a menstrual period, at which point menopause has officially been reached. (43)

On average, perimenopause begins 8-10 years before menopause. For most women, this means the menopausal transition starts in their mid-40s. Community-based studies indicate that the distribution of menopausal age displays a bell curve that ranges from age 40, ending around the age of 54, generally clustering around the ages 45-55. (4, 38)

The duration of perimenopause varies between women. Perimenopause can last from months up to 10 years, although the average time until reaching menopause is four years. (7)

Perimenopause Signs & Symptoms

Up to 70% of women experience symptoms from perimenopause through menopause (43). Levels of estrogen and progesterone shift unevenly and unpredictably through perimenopause, causing hormonal symptoms, which include:  

• Irregular periods and reduced fertility
• Hot flashes
• Insomnia
• Night sweats
• Changes in mood: depression, mood swings, and irritability
• Changes in sexual function: vaginal dryness and atrophy, painful intercourse, low libido, reduced sexual arousal, difficulty achieving orgasm
• Weight gain
• Breast tenderness
• Brain fog, forgetfulness, and difficulty concentrating (7, 30)

Reductions in estrogen levels are also associated with increased risk for vaginal and urinary tract infections, osteopenia, osteoporosis, dyslipidemia, and heart disease (39).

How to Diagnose Perimenopause

The diagnosis of perimenopause does not require lab testing and is typically made based on the patient's age and medical history. However, labs can help confirm clinical suspicions, correlate hormonal status with clinical symptomology, and personalize treatment options to optimize patient outcomes.

Step 1: Clinical History and Physical Examination

Begin with a thorough clinical history. Document menstrual irregularities and other hallmark perimenopausal symptoms. A detailed symptom diary kept by the patient can be valuable during this intake.

A comprehensive physical exam should also be performed to assess for other possible causes of symptoms, such as thyroid dysfunction or fibroids, which can mimic perimenopausal symptoms.

Step 2: Comprehensive Hormonal Evaluation

Measuring hormone levels can help confirm suspicions of perimenopause, along with drawing connections between specific patterns in hormonal imbalances and the patient's symptomology. Results that indicate reduced ovarian function include sustained elevations in FSH and LH and reductions in estradiol and progesterone. Blood work is typically ordered as first-line testing. The following panels can be an excellent starting point for laboratory evaluation: 

• Female Hormone Panel by Precision Point
• Female Hormone Panel by BostonHeart Diagnostics
• Female Serum Hormones Advanced Profile by ZRT Laboratory

However, given that hormonal levels fluctuate over time and serum hormones only represent hormonal levels at the time of the blood draw, specialty panels that measure hormones and their metabolic byproducts throughout a menstrual cycle may be better suited to detect hormonal imbalances in this population. These are popular advanced hormonal panel options: 

• DUTCH Cycle Mapping by Precision Analytical (DUTCH)
• Saliva Hormone Female Evaluator (11 Days) by Access Medical Labs
• Rhythm by Genova Diagnostics

Assessing adrenal gland function can also be an important aspect of a perimenopausal evaluation because the adrenal glands take over the production of sex hormones as ovarian function declines. Hypothalamic-pituitary-adrenal (HPA) dysfunction can exacerbate menopausal symptoms, especially insomnia, fatigue, and mood swings. These panels measure cortisol as a marker of adrenal health:

• DUTCH Complete by Precision Analytical (DUTCH)
• Sleep and Stress Panel by Ayumetrix
• Endo+ by Genova Diagnostics

Step 2: Comprehensive Health Screening

The incidence of thyroid disorders, high cholesterol, heart disease, and osteoporosis rises after menopause (31, 47). Because of this, the following tests are appropriate to order as part of a wellness screening:

• Comprehensive metabolic panel (CMP)
• Lipid panel
• Fasting glucose and insulin
• hs-CRP
• Thyroid panel

Suboptimal nutrient status can impair the body's ability to synthesize hormones (reproductive, thyroid, and adrenal) and increase the risk of osteoporosis and heart disease. A micronutrient test measures vital vitamins, minerals, amino acids, antioxidants, and fatty acids to identify nutritional imbalances impacting your patient's health. Consider ordering one of the following panels: 

• Micronutrient Test by SpectraCell
• Cellular Micronutrient Assay by Cell Science Systems 
• NutrEva FMV by Genova Diagnostics

The liver and intestines are the primary eliminatory organs responsible for metabolizing and eliminating excess hormones. Imbalances in the estrobolome, the collection of beneficial bacteria in the gut responsible for metabolizing and modulating the body's circulating estrogen, can lead to hormonal imbalances and symptoms. A comprehensive stool analysis and liver function panel provide helpful information about the status of the microbiome, digestive function for nutrient digestion/absorption, and liver function. Examples of specific tests include:

• GI-MAP by Diagnostic Solutions
• Hepatic Function Panel by Access Med Labs

[signup]

Treatment Plan for Perimenopause

Following this simplified step-by-step protocol, and customizing it as needed to each patient's individual needs, helps support women manage the distressing symptoms associated with perimenopause.

Step 1: Reduce Inflammation

Here's Why This Is Important:

Inflammation, triggered by declining estrogen levels, intensifies perimenopausal symptoms and increases the risk of chronic diseases later in life.

How Do You Do This?

Ensuring adequate and restorative sleep is fundamental in reducing inflammation. Aim for 7-9 hours of sleep per night. Tips to follow for a good night's sleep include:

• Establish a consistent sleep schedule by going to bed and waking up at the same times daily, even on weekends. 
• Create a calming bedtime routine that might include activities like reading, meditation, or taking a warm bath. 
• Ensure the sleep environment is conducive to rest: a cool, dark, and quiet room can promote better sleep. 
• Avoid electronics at least an hour before bedtime, as they can disrupt the sleep-wake cycle.

Physical inactivity can lead to the accumulation of visceral fat and the activation of systemic inflammation. Regular physical activity, therefore, helps mitigate inflammation. General recommendations suggest partaking in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise per week, complemented by muscle-strengthening activities on two or more days a week. Exercise not only reduces inflammatory markers but also improves mood, energy levels, and cardiovascular health. (52) 

Stress management is crucial as chronic stress can elevate inflammatory markers. Stress management techniques, such as mindfulness meditation, and deep breathing exercises, can help manage stress levels and lower inflammatory biomarkers. 

Adopting an anti-inflammatory diet can significantly reduce inflammation. Focus on consuming a variety of whole, unprocessed foods rich in antioxidants, vitamins, and minerals. 

• Include plenty of fruits and vegetables, particularly those high in phytonutrients, such as berries, leafy greens, and cruciferous vegetables. 
• Whole grains, nuts, seeds, and legumes should also be staples.
•  Incorporate healthy fats from olive oil, avocados, and fatty fish like salmon and sardines. 
• Avoid processed foods, refined sugars, and excessive intake of red and processed meats, as these can exacerbate inflammation.

Omega-3 fatty acids have potent anti-inflammatory effects. They can be obtained from dietary sources like fatty fish, flaxseeds, and walnuts, but supplementation may be necessary to achieve therapeutic levels. Research suggests that supplemental EPA reduces the frequency and severity of hot flashes. A typical dosage is 1,000 to 2,000 mg of combined EPA and DHA daily, though this can vary based on individual needs. 

Step 2: Support Hormonal Systems

Here's Why This Is Important:

The gut, liver, and adrenals play key roles in hormone metabolism, detoxification, and stress response. Suboptimal gastrointestinal health can impair nutrient absorption and hormone regulation, liver dysfunction can lead to the inadequate clearance of hormone metabolites, and adrenal fatigue can exacerbate symptoms of hormonal imbalance by disrupting cortisol and other hormone levels.

How Do You Do This?

Ensure digestive health is optimal and that patients are having regular, daily bowel movements. Foundational treatment recommendations for supporting optimal gut health include:

• Hydration: Stay hydrated by drinking at least half your body weight in ounces daily. Adequate hydration helps maintain healthy mucosal linings, facilitates digestion, and supports the elimination of hormone metabolites via bowel movements.
• Fiber: Consuming sufficient dietary fiber promotes regular bowel movements and a healthy gut microbiome. Aim for at least 25-30 grams of fiber daily by eating a variety of fruits, vegetables, whole grains, legumes, nuts, and seeds.
• Probiotic Supplements: Probiotics, specifically strains of the Lactobacillus species, have been researched for their positive effects on women's health and improving symptoms of hormonal imbalance. The benefits of probiotic supplements include preventing genitourinary infections, reducing vasomotor symptoms, and improving sleep quality and mood.

The following dietary modifications and supplements aim to support liver health for efficient hormone metabolism and detoxification, which can help alleviate perimenopausal symptoms and support general hormonal wellness:

• Increase antioxidant-rich foods by eating a variety of colorful fruits and vegetables to protect the liver from oxidative stress.
• Consume cruciferous vegetables, such as broccoli, kale, and Brussels sprouts. These contain compounds like I3C (indole-3-carbinol) and sulforaphane that enhance liver detoxification pathways.
• Milk thistle is a well-researched herb known for its liver-protective properties. It contains silymarin, which has antioxidant and anti-inflammatory effects and supports liver cell regeneration. A typical dosage is 150-300 mg of silymarin, taken two to three times daily.
• N-Acetyl Cysteine (NAC) is a precursor to glutathione, a critical antioxidant for liver detoxification. It helps replenish glutathione levels and supports liver function. The recommended dosage is usually 600-1200 mg daily, taken in divided doses.

In addition to fostering resiliency to stress by eating a healthy diet, prioritizing sleep, and exercising regularly, the following supplements can be used to support the adrenal glands: 

• Ashwagandha: 250-1,000 mg daily
• Rhodiola: 100-600 mg daily
• Phosphatidylserine: 100-300 mg daily
• Magnesium: 250-1,000 mg daily

Step 3: Palliate Symptoms

Here's Why This Is Important:

Symptoms experienced during perimenopause hold the capacity to significantly and negatively impact the quality of life in women undergoing this transition. Additional therapies that specifically act to reduce the frequency and severity of symptoms can provide much-needed relief to these women. 

How Do You Do This?

Hormone replacement therapy (HRT), in the form of birth control pills, skin patches, sprays, gels, and creams, delivers estrogen, progesterone, and/or testosterone to manage perimenopausal symptoms and prevent bone loss. (7, 24)

Nonhormonal pharmacologic treatment options for managing hot flashes, mood disorders, and vaginal dryness include antidepressants, gabapentin, pregabalin, and vaginal moisturizers (24).

For those with contraindications to, or personal preferences against, using pharmacologic therapies, the following natural supplements have evidence to support their use in managing perimenopausal symptoms: 

• Phytoestrogens, found in soy, beans, flax seeds, and cruciferous vegetables, are plant compounds that weakly bind to estrogen receptors and reduce menopausal symptoms (5). 
• Black cohosh, typically dosed between 40-160 mg daily, can reduce hot flashes and boost mood by modulating receptors in the central nervous system that play a role in regulating body temperature, mood, and sleep.
• 100 IU of vaginal vitamin E was found to be as effective as vaginal estrogen for treating menopause-related vaginal dryness and pain.

[signup]

Key Takeaways:

• Perimenopause is a regular part of the aging process characterized by the natural decline in ovarian function and reproductive hormones. This transition does not need to be feared.
•  A comprehensive and integrative treatment plan for perimenopausal women involves addressing multiple facets of health to effectively manage symptoms and enhance overall well-being. 
• A personalized approach provides the necessary support for women to thrive during their transition into menopause.