Hormone Optimization in Aging

The Tide Going Out

Hormones don’t crash overnight. They recede like a tide — slowly, imperceptibly at first, then one morning you notice the shoreline has moved a hundred yards. You’re tired in ways sleep doesn’t fix. Your body composition shifts despite the same habits. Your mood flattens. Your joints ache. Your libido becomes a memory. Your thinking feels like it’s running through fog.

Conventional medicine calls this “normal aging.” Functional medicine calls it what it is: a progressive endocrine deficit with identifiable markers and treatable causes.

The hormone decline cascade involves multiple axes, each influencing the others:

• Menopause (estrogen, progesterone decline) — average onset 51, but perimenopause begins 5-10 years earlier
• Andropause (testosterone decline in men) — gradual, ~1-2% per year after age 30
• Adrenopause (DHEA, cortisol rhythm disruption) — DHEA peaks around 25, declines 2-3% per year
• Somatopause (growth hormone decline) — GH secretion drops ~14% per decade after 30

These aren’t independent events. They’re interconnected cascades. Low testosterone increases cortisol. High cortisol suppresses thyroid. Low thyroid slows everything. Low DHEA impairs immune function. The dominoes fall in sequence.

Bioidentical HRT for Women

The WHI Story: What Actually Happened

The Women’s Health Initiative (WHI) trial in 2002 terrified an entire generation of women — and their doctors — away from hormone replacement therapy. But what most people don’t know is that the WHI used conjugated equine estrogens (Premarin — literally derived from pregnant horse urine) combined with medroxyprogesterone acetate (Provera — a synthetic progestin). These are not the same as human-identical hormones.

The reanalysis tells a different story:

• Women who started HRT within 10 years of menopause (the “timing hypothesis”) had reduced cardiovascular events and all-cause mortality (Rossouw 2007 reanalysis)
• The estrogen-only arm (for women without a uterus) showed decreased breast cancer risk after 13 years of follow-up (Anderson 2012)
• The Fournier 2005 French cohort study (over 80,000 women) found that bioidentical progesterone combined with estradiol showed no increased breast cancer risk, while synthetic progestins significantly increased it
• The Danish Osteoporosis Prevention Study (Schierbeck 2012) — the only RCT to start HRT in recently menopausal women — showed 50% reduction in heart failure, MI, and death over 16 years

The conclusion isn’t that hormones are dangerous. It’s that the wrong hormones, given at the wrong time, carry risks. Bioidentical hormones, initiated in the perimenopause window, have a fundamentally different risk profile.

The Bioidentical Protocol

Estradiol (17-beta estradiol — identical to what the ovary makes):

• Transdermal patch or cream preferred (bypasses first-pass liver metabolism, lower clotting risk)
• Typical dosing: 0.025-0.1mg patch, or compounded cream 0.5-2mg
• Oral micronized estradiol (Estrace) is an option but slightly increases clotting factors
• Target: symptom resolution + serum estradiol 50-200 pg/mL (individualized)

Progesterone (micronized bioidentical — Prometrium or compounded):

• 100-200mg orally at bedtime (it’s sleep-promoting — progesterone is a GABA-A agonist)
• Required for any woman with a uterus (endometrial protection)
• Benefits: sleep, mood, neuroprotection, bone density, anti-inflammatory
• Oral route preferred for sleep benefits; vaginal/topical for those with liver concerns

Testosterone for women (often overlooked):

• Women produce testosterone too — and it declines with age and after oophorectomy
• Low dose: compounded cream 0.5-2mg daily (target free testosterone in upper third of premenopausal range)
• Benefits: libido, energy, muscle mass, bone density, cognitive clarity
• Watch for: acne, hair growth (dose-dependent, usually indicates excess)

DHEA for women:

• 5-25mg daily (much lower than male dosing)
• Vaginal DHEA (Intrarosa/prasterone 6.5mg) is FDA-approved for vulvovaginal atrophy
• Supports adrenal function, immune modulation, bone density

When to Start and When to Stop

The timing hypothesis (Hodis 2016 — ELITE trial) demonstrated that estrogen therapy initiated within 6 years of menopause reduced atherosclerosis progression, while initiation more than 10 years after menopause did not. This created the “window of opportunity” concept.

Optimal timing: start in perimenopause or within 5 years of menopause. Duration: individualized, but many functional medicine practitioners support continuation indefinitely if monitoring is maintained. The risks of hormone deficiency in aging (osteoporosis, cardiovascular disease, dementia, sarcopenia, depression) may outweigh the risks of well-monitored bioidentical therapy.

Testosterone Optimization in Men

The Andropause Reality

Total testosterone in men declines approximately 1-2% per year after age 30. But it’s the free testosterone that matters clinically — and it drops faster because sex hormone-binding globulin (SHBG) increases with age, binding more testosterone and making it unavailable.

By age 70, many men have free testosterone levels that are 50-70% below their peak. The consequences ripple through every system: muscle loss, fat gain, bone weakening, mood disruption, cognitive decline, cardiovascular risk, and immune suppression.

Natural Optimization First

Before considering TRT, address the modifiable factors:

Sleep: Testosterone is primarily produced during deep sleep. Men who sleep 5 hours have testosterone levels 10-15% lower than those sleeping 8 hours (Leproult 2011). This is a non-negotiable foundation.

Body composition: Adipose tissue contains aromatase, which converts testosterone to estrogen. Losing excess body fat directly improves testosterone levels.

Zinc: Required for testosterone synthesis. 30-50mg daily (with 2mg copper for balance). Deficiency is common, especially in athletes and older adults.

Boron: 6-10mg daily. Naghii 2011 showed that one week of boron supplementation increased free testosterone by 28% and decreased estradiol by 39%.

Ashwagandha (Withania somnifera): 600mg KSM-66 extract daily. The Lopresti 2019 RCT showed 15% increase in testosterone, 18% increase in DHEA-S, and improved sexual function in aging men.

Tongkat ali (Eurycoma longifolia): 200-400mg standardized extract daily. Multiple trials show modest testosterone increases and significant improvements in stress hormones (cortisol reduction — Talbott 2013).

Vitamin D: Optimize to 50-80 ng/mL. Pilz 2011 showed testosterone increased significantly in vitamin D-deficient men receiving supplementation over one year.

Resistance training: Heavy compound movements (squats, deadlifts, presses) with adequate recovery are the most powerful natural testosterone stimulus.

Testosterone Replacement Therapy

When natural optimization is insufficient (total testosterone consistently <350 ng/dL or free testosterone below range with symptoms):

Methods:

• Topical gel/cream: Most common. Applied daily. Compounded or commercial (AndroGel, Testim). Allows dose titration.
• Intramuscular injections: Testosterone cypionate or enanthate, 50-100mg twice weekly (smaller, more frequent doses maintain more stable levels than large weekly injections)
• Subcutaneous injections: Same compounds, smaller needle, less muscle soreness. Growing in popularity.
• Pellets (Testopel): Implanted every 3-6 months. Steady state but less flexibility for dose adjustment.

Monitoring (every 3-6 months initially, then annually):

• Total and free testosterone (target upper third of reference range)
• Estradiol (watch for aromatase-driven elevation — target 20-35 pg/mL)
• Hematocrit/hemoglobin (TRT stimulates erythropoiesis — donate blood if hematocrit >52%)
• PSA (prostate screening — TRT does not cause prostate cancer per Morgentaler’s saturation model, but monitor)
• Lipid panel
• Liver function

Fertility preservation:

• Exogenous testosterone suppresses spermatogenesis (via HPG axis suppression)
• For men wanting to preserve fertility:
  • Clomiphene citrate: 25-50mg daily or every other day. Blocks estrogen feedback at the pituitary, stimulating LH and FSH → endogenous testosterone production. Off-label but well-studied.
  • Enclomiphene (the trans-isomer of clomiphene): Cleaner pharmacology, fewer side effects, being developed specifically for male hypogonadism.
  • HCG (human chorionic gonadotropin): 500-1000 IU 2-3x weekly. Mimics LH, maintains testicular function and fertility alongside TRT or as standalone.

Growth Hormone: The Regeneration Signal

Growth hormone (GH) secretion declines approximately 14% per decade after age 30. By 60, many adults have GH levels comparable to GH-deficient patients. The consequences: increased visceral fat, decreased lean mass, reduced bone density, impaired wound healing, thinning skin, poor sleep quality, and reduced exercise capacity.

Optimizing IGF-1 Without Exogenous GH

Injecting recombinant human GH is expensive ($500-1500/month), carries risks (insulin resistance, joint pain, potential cancer concern with supraphysiological IGF-1), and is legally restricted. Fortunately, robust natural strategies exist:

Sleep architecture: The largest GH pulse occurs during the first bout of deep (slow-wave) sleep, typically within 90 minutes of falling asleep. Anything that impairs deep sleep — alcohol, late eating, blue light, sleep apnea — directly suppresses GH.

Exercise: Both resistance training and HIIT significantly increase GH release. Higher intensity and shorter rest periods drive greater GH response.

Fasting: GH increases dramatically during fasting — up to 5-fold during a 2-day fast (Ho 1988). Even intermittent fasting (16:8) enhances the nocturnal GH pulse.

Peptide secretagogues (physician-prescribed, compounded):

• Ipamorelin: Growth hormone-releasing peptide. 100-300mcg at bedtime subcutaneously. Stimulates pulsatile GH release without significant cortisol or prolactin elevation.
• CJC-1295 (no DAC): Growth hormone-releasing hormone analog. Often combined with ipamorelin for synergistic effect. 100-200mcg at bedtime.
• Tesamorelin: FDA-approved GHRH analog (for HIV lipodystrophy, used off-label). Reduces visceral fat, improves body composition.

Target: IGF-1 in the upper third of the age-adjusted reference range (approximately 150-250 ng/mL for most adults). Monitor fasting glucose and insulin — GH can worsen insulin resistance at high levels.

Thyroid in Aging

Thyroid function subtly declines with age, but the standard TSH-only screening misses most of it. The issue is often not reduced thyroid hormone production but impaired conversion of T4 (the storage form) to T3 (the active form).

T4-to-T3 conversion requires:

• Selenium: 200mcg daily. The deiodinase enzymes that convert T4 to T3 are selenoenzymes. Selenium deficiency is common in aging.
• Zinc: 30mg daily. Required for T3 receptor binding.
• Iodine: 150-300mcg daily (RDA is 150mcg; many practitioners use slightly more). Excessive iodine can worsen autoimmune thyroid disease — proceed cautiously.
• Iron: Ferritin >70 ng/mL is needed for optimal thyroid function.
• Cortisol balance: Both excess and deficient cortisol impair T4-to-T3 conversion.

Full thyroid panel (not just TSH): TSH, free T4, free T3, reverse T3, thyroid antibodies (TPO, thyroglobulin). Optimal functional ranges: TSH 0.5-2.0 mIU/L, free T3 upper half of range, reverse T3 <15 ng/dL, rT3/fT3 ratio <10.

DHEA and Pregnenolone: The Mother Hormones

DHEA (dehydroepiandrosterone) is the most abundant steroid hormone in the body and the precursor from which testosterone, estrogen, and dozens of other hormones are synthesized. Pregnenolone sits even higher in the cascade — it’s the first hormone made from cholesterol and the precursor to DHEA, progesterone, cortisol, and all downstream hormones.

Both decline with age:

• DHEA peaks around age 25 and declines 2-3% annually. By 70, levels are 10-20% of peak.
• Pregnenolone follows a similar trajectory.

DHEA supplementation:

• Men: 25-50mg daily (morning, as it can be stimulating)
• Women: 5-25mg daily
• Monitor DHEA-S levels, testosterone, and estrogen
• Benefits: immune modulation, bone density, mood, cognitive function, adrenal support

Pregnenolone supplementation:

• 10-50mg daily (morning or divided)
• Particularly valuable as a neurosteroid — enhances memory, mood, and stress resilience
• Start low, as it can convert preferentially down either the cortisol or sex hormone pathway depending on individual need

Oxytocin: The Forgotten Aging Hormone

Oxytocin — the “love hormone” — is rarely discussed in aging, but it should be. It declines with age, and its decline correlates with social isolation, depression, muscle loss, and impaired wound healing. Oxytocin receptors are found throughout the brain, gut, heart, and immune system.

Research is emerging that oxytocin may be a genuine anti-aging hormone:

• Elabd et al. (2014) showed oxytocin restored muscle regeneration in aged mice
• It opposes cortisol and reduces systemic inflammation
• It enhances gut barrier function and modulates the immune response
• Low oxytocin correlates with cardiovascular disease risk

Natural oxytocin boosters: Physical touch, social bonding, singing in groups, pet interaction, massage, warm baths, meditation, orgasm.

Supplemental oxytocin: Intranasal oxytocin (10-40 IU) is available by prescription through compounding pharmacies. Used in some longevity protocols, though research is still emerging. Some functional medicine practitioners prescribe it for social anxiety, gut healing, and as part of comprehensive anti-aging protocols.

Testing Cadence and Monitoring

Baseline (comprehensive):

• Full hormone panel: estradiol, progesterone, total and free testosterone, SHBG, DHEA-S, pregnenolone, cortisol (4-point salivary or DUTCH), full thyroid, IGF-1, fasting insulin
• Metabolic markers: fasting glucose, HbA1c, lipid panel, hs-CRP
• CBC (baseline hematocrit for TRT monitoring)
• PSA (men)
• Bone density (DEXA) baseline

Follow-up (every 3-6 months while titrating):

• Hormones being replaced + downstream metabolites
• Safety markers: hematocrit, liver function, lipids, PSA
• Symptom assessment (standardized questionnaires for quality of life)

Maintenance (annually once stable):

• Full hormone panel
• Complete metabolic and safety markers
• DEXA every 2 years
• Cognitive assessment (MoCA or equivalent)

The Integration

Hormones don’t work in silos. Optimizing testosterone without addressing thyroid is like tuning one instrument in an orchestra. The IFM approach treats the entire endocrine system as an interconnected web — because it is.

The goal isn’t to recreate the hormone levels of a 25-year-old. It’s to find the individual’s optimal range — the levels at which they feel sharp, strong, resilient, and vital, while maintaining safety. This requires partnership between an informed patient and a practitioner willing to test, monitor, adjust, and listen.

The tide doesn’t have to keep going out. With the right map and the right tools, you can hold the water.

When did you first notice the tide receding — and what did you tell yourself about it?