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Cofactor + NAD+ substrate + GH-axis (adjunct to HRT)

Menopause Support

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This protocol is for women in perimenopause or postmenopause who want peptide-based ADJUNCT support alongside (or in place of) hormonal management. The most important editorial point: hormone replacement therapy — HRT, also called menopausal hormone therapy (MHT) — is the evidence-based first-line treatment for vasomotor symptoms (hot flashes, night sweats), genitourinary syndrome of menopause, perimenopausal mood symptoms, and bone density preservation. The 2022 NAMS Position Statement and the Women's Health Initiative re-analyses have largely re-positioned HRT as the appropriate first-line therapy for symptomatic women within ~10 years of menopause without contraindications. This protocol is NOT a substitute for that conversation with your gynecologist or menopause-specialist clinician.

The protocol assumes you have already had the HRT discussion and either (a) chosen HRT and want peptide adjuncts for body composition, cognitive, or energy support layered on top; or (b) chosen against HRT (for personal or medical reasons) and want non-hormonal support; or (c) are not yet a candidate for HRT (some users in early perimenopause with intact cycles) and want cofactor-level support.

It is NOT for users with active breast cancer, hormone-receptor-positive cancer history (HARD EXCLUSION for Phase 3 GH-axis), unprovoked DVT/PE history without anticoagulation evaluation, or untreated severe cardiovascular disease. It is NOT a substitute for bone-health management — osteoporosis warrants bisphosphonates, denosumab, or other targeted therapy, NOT peptide adjuncts.

Phases

  1. Phase 1 — Baseline workup + cofactor foundation (B12)

    weeks 1-4

    Get the baseline labs in hand BEFORE peptide adjustments — FSH, estradiol (E2 sensitive assay), TSH + free T4, lipid panel, fasting glucose + A1c, vitamin D, ferritin, CBC, and consider DEXA scan if 50+ or risk factors. The labs inform the HRT-vs-no-HRT conversation AND screen for the common menopause-symptom mimics (thyroid dysfunction, iron deficiency, vitamin D deficiency, B12 deficiency — all common in midlife women and all present with overlapping fatigue + cognitive symptoms). B12 1000mcg SubQ weekly addresses the most common cofactor deficiency that mimics 'menopause fatigue.'

    • B12 (Methylcobalamin)1 mg · once weekly · morning

      1000mcg SubQ once weekly. Methylcobalamin form. Many users in this cohort have B12 in the lower normal range (200-400 pg/mL) which can drive fatigue and cognitive symptoms that get attributed to menopause; addressing it first prevents misattribution and clarifies whether peptide work is even needed beyond cofactor repletion.

    What “working” looks like

    Modest energy + cognitive clarity over 4-6 weeks. Lab results in hand for the gynecologic conversation. No expectation of VMS improvement (B12 doesn't address hot flashes or night sweats — those need HRT or non-hormonal alternatives like SSRIs/SNRIs, gabapentin, or fezolinetant). Mood baseline may shift modestly if B12 was contributing.

    Decision criteria

    After 4 weeks: review labs with your gynecologist or menopause specialist. Outcomes determine the path: (a) HRT indicated and chosen → continue Phase 1 cofactors alongside HRT; consider Phase 2-3 layering; (b) HRT contraindicated (breast cancer history, active CV disease, etc.) → continue Phase 1; Phase 2-3 evaluation with specialist input; (c) HRT declined (personal choice) → continue Phase 1; Phase 2 reasonable to layer; (d) Thyroid / iron / D-deficiency identified → address THOSE first; peptide work is secondary.

    Labs to pull

    • FSH, estradiol (E2 sensitive assay)
    • TSH, free T4 (thyroid is the most common menopause-symptom mimic; treat it first if abnormal)
    • Lipid panel + fasting glucose + A1c (cardiometabolic baseline as ovarian estrogen support declines)
    • 25-OH vitamin D (commonly deficient; affects bone + mood)
    • Ferritin + CBC (iron deficiency commonly persists from heavy perimenopausal bleeding even after cycles stop)
    • B12 + RBC folate
    • DEXA scan if 50+ or risk factors (early postmenopause is the highest-leverage window for bone-density baseline)

  2. Phase 2 — NAD+ substrate layer (+NR)

    weeks 4-12 (continue Phase 1)

    OPTIONAL. Add nicotinamide riboside (NR) 500mg orally once daily for users with energy + metabolic + cardiovascular goals. NR consistently raises whole-blood NAD+ levels at 250-1000mg/day across multiple RCTs (the biomarker effect is robust); whether the NAD+ rise translates to clinically meaningful changes in metabolic health or cognition has produced largely null-to-modest results. The honest framing: this is mechanism-plus-biomarker, not validated clinical-outcome work. Continue Phase 1 B12.

    • B12 (Methylcobalamin)1 mg · once weekly · morning

      Continue Phase 1 cofactor.

    • Nicotinamide Riboside (NR)500 mg · once daily · morning

      500mg (= 500,000mcg) oral once daily — middle of the clinical-trial range (250-1000mg/day). Morning dosing is community standard; some users prefer split-dosing (250mg AM + 250mg PM). Take with or without food.

    What “working” looks like

    Modest energy + workout-recovery shift over 4-8 weeks. Modest improvement in arterial stiffness / systolic blood pressure if baseline BP was elevated (Martens 2018 showed ~6 mmHg reduction in older adults with elevated baseline BP — that's the strongest published clinical signal). No expectation of dramatic cognitive change. NO menopausal symptom benefit (NR doesn't treat hot flashes, GSM, mood symptoms — those need HRT or non-hormonal alternatives).

    Decision criteria

    After 8-12 weeks: if you have meaningful subjective energy + workout-recovery improvement OR objective BP/lipid improvement, this is your working dose — continue. If no clear delta after 12 weeks, the editorial honesty is that NR's clinical-outcome data is mixed and your physiology may not be a responder — discontinue rather than escalating dose.

    Labs to pull

    • Lipid panel + fasting glucose + A1c re-check at 12 weeks (the metabolic indications NR is most-studied for)
    • Blood pressure trend (the Martens 2018 indication)

  3. Phase 3 — GH-axis body comp + cognitive layer (+CJC/Ipa)

    weeks 12+, layered on Phase 1+2

    OPTIONAL. Add CJC-1295 / Ipamorelin 250/250mcg SubQ 5 days/week before bed (fasted 2+ hours) for postmenopausal users whose body-composition goals weren't addressed by Phase 1+2 alone. Postmenopausal body composition shifts (visceral fat redistribution, accelerated lean-mass loss, declining bone density) reflect both estrogen decline AND age-related GH/IGF-1 decline; the GH-axis layer addresses the second of those drivers. NOT for users with breast cancer history — hard exclusion. Continue Phase 1+2 throughout.

    • B12 (Methylcobalamin)1 mg · once weekly · morning

      Continue Phase 1 cofactor.

    • Nicotinamide Riboside (NR)500 mg · once daily · morning

      Continue Phase 2 NAD+ substrate.

    • CJC-1295 / Ipamorelin250 mcg · 5 days per week · before bed, fasted 2+ hours

      10 units SubQ (250mcg CJC + 250mcg Ipa) 5 days/week, before bed, fasted 2+ hours. Insulin from a recent meal blunts the ghrelin-pathway response, so dose fasted. Standard community blend pattern.

    What “working” looks like

    IGF-1 rises (pull at 8 weeks to confirm on-target). Modest body-composition shifts at 12-16 weeks — visceral fat redistribution, modest lean-mass support, modest improvement in body-recomposition trajectory. Sleep quality improves (GH peaks in slow-wave sleep). No effect on hot flashes / VMS / GSM — those remain HRT's domain.

    Decision criteria

    At week 12-16: re-check IGF-1, fasting glucose, A1c. If IGF-1 rose appropriately + body composition shifted: continue with cycling (8-12 weeks on, 4-8 weeks off). If IGF-1 didn't move: troubleshoot reconstitution + timing (meal-proximity insulin blunting is the most common issue). Long-term continuous GH-secretagogue use in postmenopausal women is not well-characterized for safety — cycle off rather than running indefinitely.

    Labs to pull

    • IGF-1 (on-target marker for GH-axis stimulation)
    • Fasting glucose + A1c (GH is counter-regulatory to insulin; postmenopausal users may have heightened insulin-resistance baseline)
    • Mammogram on schedule per usual care (not changed by this protocol but the cohort overlap means consistent breast surveillance matters)

Cautions

  • HRT (menopausal hormone therapy) is the EVIDENCE-BASED FIRST-LINE for vasomotor symptoms, GSM, perimenopausal mood symptoms, and bone density preservation. This protocol does NOT treat hot flashes, night sweats, vaginal atrophy, or sexual-symptom GSM — those need HRT or non-hormonal alternatives (SSRIs/SNRIs, gabapentin, fezolinetant for VMS; vaginal estrogen for GSM). If you have these symptoms and have not had the HRT discussion with a gynecologist or menopause specialist, that conversation is the high-leverage intervention — not adding more peptides.
  • Active breast cancer or hormone-receptor-positive cancer history is a HARD EXCLUSION for Phase 3 (CJC/Ipa). The IGF-1 elevation is the theoretical concern in hormone-sensitive tissues. Phase 1+2 may still be appropriate but require oncology team input. Phase 3 is off-table without explicit oncology approval (rarely given).
  • Unprovoked DVT/PE history or known thrombophilia: while this protocol does not include estrogen, the underlying thromboembolic risk picture is relevant to any future HRT decision and to overall cardiovascular monitoring. If you have this history, the HRT conversation with your specialist needs to address anticoagulation evaluation regardless of this protocol; Phase 2-3 should not proceed without that broader evaluation.
  • Active severe cardiovascular disease (recent MI, unstable angina, severe heart failure) is a contraindication. GH-axis stimulation has complex cardiovascular interactions; the safety calculus belongs with a cardiologist, not a community protocol.
  • Osteoporosis (T-score ≤ -2.5 on DEXA) requires targeted treatment — bisphosphonates, denosumab, romosozumab, or other anti-resorptive / anabolic bone therapy. This protocol is NOT a substitute for osteoporosis treatment; relying on it instead of indicated therapy carries significant fracture risk over time.
  • Perimenopausal users with intact (even if irregular) cycles can still conceive — anovulatory cycles are not 100% anovulatory. Phase 3 (CJC/Ipa) is contraindicated in pregnancy; if there is any possibility of pregnancy, contraception must be addressed BEFORE Phase 3. Phase 1+2 are not pregnancy-tested individually but Phase 1 cofactors are routine in pregnancy supplementation (B12 is standard prenatal).
  • Postmenopausal users with new abnormal bleeding need OB-GYN workup BEFORE peptide changes — postmenopausal bleeding is a red flag (endometrial cancer must be ruled out) and is not a 'menopause symptom' to be managed with peptides.
  • Pediatric exclusion. This protocol is for adult women, typically 40+ in perimenopause through postmenopause.

Discuss with your clinician

  • Have the HRT conversation with a gynecologist or menopause-specialist clinician BEFORE starting peptide adjuncts. The conversation should cover: symptom severity (VMS, GSM, mood, sleep, cognitive), individual risk factors (breast cancer family history, CV risk, thromboembolic history), age + time since menopause (the timing-hypothesis window matters), preferences (oral vs transdermal, MPA vs micronized progesterone, etc.), and contraindications. The NAMS-certified menopause practitioner directory at menopause.org is the best source for clinicians genuinely current on the post-WHI re-analysis.
  • Order Phase 1 labs at baseline: FSH + E2, TSH + free T4, lipid panel, fasting glucose + A1c, vitamin D, ferritin + CBC, B12. Add DEXA scan if 50+ or any risk factors (low body weight, smoking history, family history of fragility fracture, glucocorticoid use, malabsorption). DEXA in early postmenopause is the highest-leverage bone-density baseline window.
  • Address modifiable cardiometabolic risk in parallel — lipid panel, BP, fasting glucose, A1c. The metabolic-cardiovascular risk window opens as ovarian estrogen support declines; this is a higher-leverage focus than peptide stack optimization for most users.
  • If you have any breast cancer family history (first-degree relative with breast or ovarian cancer at any age, or two second-degree relatives with breast cancer), discuss genetic counseling and possibly BRCA testing BEFORE Phase 3. The hormonal-axis decisions including peptide use change significantly with confirmed pathogenic variant status.
  • Mammogram on usual schedule regardless of this protocol. If on Phase 3 (GH-axis), some clinicians prefer annual rather than biennial mammography during the active cycle — discuss with your primary care or breast clinic.
  • Pelvic floor PT referral if you have GSM-related dyspareunia, urinary incontinence, or pelvic heaviness. These are not addressed by this protocol; PT + vaginal estrogen (when appropriate) are high-leverage interventions.
Evidence summary

Tier 3 protocol overall. Phase 1 (B12 + baseline workup) is Tier 2 for the deficiency-replacement indication. Phase 2 (NR) is Tier 2 for the biomarker effect (NAD+ elevation — robust across multiple RCTs); Tier 3 for any clinical-outcome claim (cardiovascular reductions are modest and not consistently replicated; cognitive + metabolic outcomes are mixed-to-null). Phase 3 (CJC/Ipa) is Tier 2 for GH/IGF-1 axis restoration based on component PK/PD data; Tier 3 for body-composition outcomes specifically in postmenopausal women (no combination RCT in this population). The protocol's strongest evidence is Phase 1 cofactor work and Phase 2's biomarker effect; the weakest is Phase 3 body-comp outcomes. None of these phases address vasomotor symptoms, GSM, or bone density — HRT is the evidence-based first-line for those, and this protocol's evidence base does NOT compete with HRT's for the indications HRT targets.

Components (3)

Often combined with

  • Energy & Vitality

    B12 + NR overlap with Energy Phase 1-2. If you're running both protocols, do NOT double-dose — single B12 weekly + NR daily covers both surfaces. Many postmenopausal users running Menopause Support also benefit from the broader Energy framing as ovarian-estrogen-decline contributes to fatigue independently of B12/NR status.

  • Longevity

    NR overlap with Longevity Phase 1. If running both protocols, do NOT double-dose NR — single 500mg/day covers both surfaces. The mTOR-vs-IGF1 tension flagged in Andropause also applies here if both Phase 3 layers (Longevity rapamycin + Menopause CJC/Ipa) are active — running both is mechanistically incoherent; choose one priority at a time.

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