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Peptides for Perimenopause & Menopause

Perimenopause and menopause affect roughly 1.3 billion women worldwide. The symptoms --- hot flashes, sleep disruption, weight gain, brain fog, bone loss, mood swings --- can last years and range from mildly annoying to life-altering.

Perimenopause and menopause affect roughly 1.3 billion women worldwide. The symptoms --- hot flashes, sleep disruption, weight gain, brain fog, bone loss, mood swings --- can last years and range from mildly annoying to life-altering.

Standard hormone replacement therapy (HRT) works well for many women, but not everyone can take it. Others want additional support beyond estrogen and progesterone alone. That's where peptide therapy enters the conversation.

This guide breaks down which peptides have real research behind them for menopausal symptoms, which ones show promise but lack strong human data, and what you should know before considering any of them.

Table of Contents

What Happens During Perimenopause and Menopause {#what-happens-during-perimenopause-and-menopause}

Perimenopause typically starts in your early-to-mid 40s, though some women notice changes in their late 30s. It's the phase when your ovaries gradually produce less estrogen and progesterone. Your periods become irregular. Symptoms show up.

Menopause itself is a single point in time --- 12 consecutive months without a period. Everything after that is postmenopause.

But the biological changes run deeper than hormones alone. Declining estrogen affects:

  • Metabolism --- Women can lose up to 0.5% of lean mass per year during the menopausal transition, while fat mass (especially visceral belly fat) increases [1]
  • Bone density --- Women can lose 10--20% of bone mass in the first five years around menopause [2]
  • Brain function --- Estrogen receptors exist throughout the brain, and declining levels affect memory, focus, and mood regulation
  • Gut health --- Estrogen helps maintain gut barrier integrity, and its decline can affect the microbiome and intestinal permeability
  • Growth hormone --- GH secretion, already declining with age, drops more sharply during menopause
  • Sleep --- Changes in thermoregulation (hot flashes, night sweats) disrupt sleep architecture

The neuropeptide system also shifts. Kisspeptin neurons (called KNDy neurons) in the hypothalamus, which regulate GnRH pulses, undergo changes during reproductive aging. These same neurons are now believed to drive vasomotor symptoms like hot flashes [3].

Why Peptides Are Getting Attention {#why-peptides-are-getting-attention}

Peptides are short chains of amino acids that act as signaling molecules in the body. Some stimulate your own hormone production rather than replacing hormones directly. Others target specific pathways --- gut repair, mitochondrial function, tissue healing --- that standard HRT doesn't address.

For perimenopausal and menopausal women, this is relevant because:

  1. Not all symptoms come from low estrogen alone. Mitochondrial dysfunction, gut inflammation, and growth hormone decline all contribute.
  2. Some peptides work alongside HRT. They don't replace estrogen therapy but may address symptoms that HRT alone doesn't fully resolve.
  3. Certain peptides have FDA-approved applications (like semaglutide for weight management and tesamorelin for visceral fat reduction).

That said, a critical disclaimer: the clinical evidence for most peptides specifically in menopausal populations is thin. Major clinical guidelines don't endorse peptide therapy for menopause symptoms. Much of the current use comes from integrative medicine clinics extrapolating from related research.

Peptides With Clinical Evidence for Menopausal Concerns {#peptides-with-clinical-evidence-for-menopausal-concerns}

Semaglutide: Menopausal Weight Management {#semaglutide-menopausal-weight-management}

Up to 70% of women experience weight gain during the menopausal transition. Metabolism slows, lean mass declines, and visceral fat accumulates --- all driven partly by falling estrogen levels [1].

Semaglutide, a GLP-1 receptor agonist, is one of the few peptide-based medications with direct clinical data in menopausal women.

What the research shows:

A 2024 Mayo Clinic retrospective study of 106 postmenopausal women on semaglutide found that those also using hormone therapy lost approximately 30% more weight than those on semaglutide alone at 3, 6, 9, and 12 months. The HT group achieved 16% total body weight loss --- comparable to results in the pivotal semaglutide trials [4].

A separate study in Metabolic Syndrome and Related Disorders found that postmenopausal women on low-dose semaglutide (1 mg) lost a comparable amount of weight to premenopausal women after four months, despite starting with higher fat mass [5].

A 2025 RAND analysis noted that women aged 50--64 have the highest GLP-1 use overall, with 20% reporting current or past use. But this same analysis raised important concerns: GLP-1 drugs reduce both fat and muscle mass, and perimenopausal women already face natural declines in both. Discontinuation typically causes weight regain --- primarily as fat, resulting in a less favorable body composition than before treatment [6].

What this means for you: Semaglutide has the strongest clinical evidence of any peptide for menopausal weight management. But the muscle loss concern is real, especially during a life stage when preserving lean mass matters most. Resistance training isn't optional --- it's required.

Collagen Peptides: Bone Density and Skin {#collagen-peptides-bone-density-and-skin}

Collagen peptides are among the most studied peptides in postmenopausal women, particularly for bone health.

Bone density findings:

A 2018 randomized, double-blind, placebo-controlled trial gave 131 postmenopausal women (ages 46--80) either 5 grams of specific collagen peptides or placebo daily for 12 months. The collagen group showed significant increases in bone mineral density at both the spine and femoral neck compared to placebo, along with favorable shifts in bone markers --- increased formation marker P1NP and reduced degradation marker CTX-1 [7].

A four-year follow-up of the same cohort found continued improvements: 5.79% and 4.21% increases in spine and femoral neck BMD, respectively [8].

A 2025 meta-analysis in Frontiers in Nutrition confirmed that collagen peptide supplementation --- especially when combined with calcium and vitamin D --- significantly improves bone mineral density in at-risk populations like postmenopausal women [9].

Skin and genitourinary health:

Estrogen decline causes measurable changes in skin thickness, elasticity, and moisture. A clinical study of 32 postmenopausal women (mean age 54) found that topical application of heptapeptide-7, a wound-healing peptide fragment, improved forehead wrinkles and skin texture [10].

A 2025 pilot study also explored oral collagen peptides combined with vulvovaginal radiofrequency therapy for genitourinary syndrome of menopause, though results from that trial are still preliminary [11].

What this means for you: Collagen peptides are one of the better-supported options for postmenopausal bone health. They won't replace calcium, vitamin D, or weight-bearing exercise, but they may offer additional protection.

Sermorelin: Growth Hormone Support {#sermorelin-growth-hormone-support}

Growth hormone declines with age in everyone, but the drop accelerates during menopause. Lower GH levels contribute to reduced lean mass, increased visceral fat, decreased bone density, impaired sleep quality, and reduced skin elasticity.

Sermorelin is a synthetic analog of growth hormone-releasing hormone (GHRH) --- the first 29 amino acids of the native hormone. Instead of injecting growth hormone directly, sermorelin stimulates your pituitary gland to release GH in its natural pulsatile pattern [12].

What the research shows:

Sermorelin has been studied primarily for adult growth hormone deficiency rather than menopause specifically. But the clinical observations overlap:

  • It preserves the GH neuroendocrine axis (the feedback system that direct GH injections can suppress)
  • It stimulates pituitary gene transcription of GH messenger RNA, maintaining pituitary reserve [12]
  • Direct GH therapy in postmenopausal women has shown a 14% increase in bone mineral content in some studies, suggesting that stimulating your own GH production may have similar (though possibly more modest) effects
  • Body composition studies show increases in lean body mass and decreases in body fat percentage

Sermorelin has not been shown to directly change estrogen levels. Some women use it alongside standard HRT, and the available data suggests both can be used together safely [12].

Timeline: Effects typically take 3--6 months to notice. Most protocols use subcutaneous injections before bed to align with natural GH peaks.

Kisspeptin: The Hormone Regulator {#kisspeptin-the-hormone-regulator}

Kisspeptin sits at the top of the reproductive hormone chain. KNDy neurons in the hypothalamus release kisspeptin, which triggers GnRH, which stimulates LH and FSH from the pituitary, which drives estrogen production from the ovaries.

During menopause, as ovarian function declines, KNDy neuron activity actually increases --- the hypothalamus is essentially trying harder to stimulate ovaries that can no longer respond [3].

What the research shows:

Most kisspeptin research has focused on men and on women with hypothalamic amenorrhea or fertility issues rather than menopause directly. However, the science is relevant:

  • A 2011 clinical study showed that kisspeptin-10 potently stimulates LH and increases pulse frequency in healthy subjects [13]
  • Research into KNDy neurons has confirmed that changes in these cells occur as part of normal reproductive aging, and their hyperactivity during menopause may contribute to hot flashes [3]
  • Gonadorelin, a synthetic GnRH analog that works downstream from kisspeptin, is sometimes used in perimenopausal women to stimulate LH and FSH release --- though its short half-life (2--20 minutes) limits practical application

What this means for you: Kisspeptin is more scientifically interesting than practically useful for menopausal women right now. The research helps explain why menopause symptoms happen, and future kisspeptin-based therapies (like longer-acting analogs such as MVT-602) may eventually offer new treatment options.

Peptides With Emerging But Limited Evidence {#peptides-with-emerging-but-limited-evidence}

BPC-157: Gut Health and Inflammation {#bpc-157-gut-health-and-inflammation}

Estrogen decline affects gut barrier integrity, and many perimenopausal women report new digestive issues --- bloating, food sensitivities, and changes in bowel habits.

BPC-157 is a peptide fragment derived from a protein found in gastric juice. Animal studies show it protects against gut lesions, accelerates healing in the stomach and intestines, and reduces inflammatory cytokines [14]. It also modulates the brain-gut axis, with preclinical research showing anxiolytic and antidepressant effects [14].

The limitation: No clinical trials exist in menopausal women. Most evidence comes from animal studies. BPC-157 is not FDA-approved for human use.

Why it's worth watching: If future human trials confirm the gut-healing and anti-inflammatory effects seen in animals, BPC-157 could address a gap that HRT doesn't --- the gut and inflammatory changes that accompany the menopausal transition.

MOTS-c: Mitochondrial Energy {#mots-c-mitochondrial-energy}

Fatigue is one of the most common complaints during perimenopause, and it's not always explained by poor sleep alone. Mitochondrial function declines with age, and estrogen plays a role in mitochondrial efficiency.

MOTS-c is a peptide encoded by mitochondrial DNA (not nuclear DNA, making it unusual). It activates the AMPK pathway --- a master regulator of energy balance --- and promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis [15].

In animal studies, MOTS-c has prevented ovariectomy-induced metabolic disturbances (a model for surgical menopause), improved insulin sensitivity, and promoted the conversion of white fat to metabolically active brown fat [15].

Circulating MOTS-c levels decline with age, and human studies show that regular exercise increases MOTS-c expression in skeletal muscle [16].

The limitation: Human clinical trials for MOTS-c in menopausal women don't exist yet. The animal data is compelling but preliminary.

GHK-Cu: Skin and Tissue Repair {#ghk-cu-skin-and-tissue-repair}

GHK-Cu (glycyl-l-histidyl-l-lysine copper complex) is a naturally occurring peptide in human blood that declines with age. It stimulates collagen production, promotes wound healing, and has demonstrated anti-inflammatory and antioxidant properties.

For postmenopausal skin --- which loses thickness, elasticity, and moisture due to estrogen decline --- GHK-Cu may offer topical support. It's one of the few peptides with established use in skincare, though most studies focus on wound healing and general skin aging rather than menopause-specific applications.

Peptide Comparison Table {#peptide-comparison-table}

PeptidePrimary Menopausal UseEvidence LevelFDA StatusRoute
SemaglutideWeight managementStrong (clinical trials in postmenopausal women)FDA-approved for obesity/T2DInjection or oral
Collagen peptidesBone density, skinModerate (RCTs in postmenopausal women)Generally recognized as safe (supplement)Oral
SermorelinGH support, body composition, boneModerate (GH deficiency studies, not menopause-specific)Previously FDA-approved (diagnostic)Injection
KisspeptinHormone regulationPreclinical/early clinicalNot approvedInjection
BPC-157Gut health, inflammationPreclinical (animal studies)Not approvedInjection or oral
MOTS-cEnergy, metabolismPreclinical (animal studies)Not approvedInjection
GHK-CuSkin repairModerate (topical skin studies)Cosmetic useTopical
TesamorelinVisceral fat reductionStrong (RCTs, though in HIV population)FDA-approved (HIV lipodystrophy)Injection

The Neuropeptide Connection: CGRP and Hot Flashes {#the-neuropeptide-connection-cgrp-and-hot-flashes}

This section isn't about peptide therapy but about a peptide that may explain one of menopause's most frustrating symptoms.

Calcitonin gene-related peptide (CGRP) is a powerful vasodilator found throughout the nervous system. Postmenopausal women who experience hot flashes have significantly higher plasma CGRP levels than those who don't [17]. Several studies show that CGRP's ability to increase skin temperature and widen blood vessels gets stronger when sex hormones are low [17].

This matters because CGRP receptor antagonists (already used for migraines) may eventually be studied for menopausal hot flashes. Current evidence strongly proposes that CGRP antagonism could help with vasomotor symptoms, cardiovascular risk, and mood disorders in postmenopausal women [17].

Peptides vs. HRT: Not Either/Or {#peptides-vs-hrt-not-eitheror}

This isn't a competition. If you're a candidate for HRT and your symptoms are driven primarily by estrogen decline, HRT remains the most direct and well-studied intervention.

Peptides may make sense:

  • Alongside HRT --- for symptoms that estrogen alone doesn't fully address (body composition changes, gut issues, energy, skin aging)
  • When HRT isn't an option --- due to history of certain cancers, blood clots, or personal preference
  • For specific goals --- like postmenopausal bone health (collagen peptides) or weight management (semaglutide)

The Mayo Clinic semaglutide study actually reinforces this "both/and" approach: women using semaglutide and hormone therapy lost more weight than those using semaglutide alone [4].

For a broader look at peptide combinations, see our peptide stacking guide. And for more on how peptides support women's health broadly, explore our guides on best peptides for hormonal balance in women and best peptides for women over 40.

Safety Considerations {#safety-considerations}

  • FDA-approved peptides (semaglutide, tesamorelin) have established safety profiles from large clinical trials
  • Collagen peptides have a strong safety record as supplements
  • Research peptides (BPC-157, MOTS-c, kisspeptin analogs) lack long-term human safety data
  • Growth hormone secretagogues (sermorelin, CJC-1295, ipamorelin) should be used under medical supervision with regular IGF-1 monitoring
  • Drug interactions are possible, particularly with diabetes medications, blood thinners, and hormone therapies
  • Always work with a healthcare provider who can monitor labs and adjust protocols

FAQ {#faq}

Can peptides replace hormone replacement therapy for menopause? No. Peptides and HRT work through different mechanisms. HRT directly replaces declining estrogen and progesterone. Most peptides target downstream effects (weight gain, bone loss, GH decline) rather than the primary hormonal cause. Some women use both together.

Which peptide has the strongest evidence for menopausal weight gain? Semaglutide has the most robust data, including studies specifically in postmenopausal women. The 2024 Mayo Clinic study showed that combining semaglutide with hormone therapy improved weight loss results [4].

Are collagen peptides worth taking after menopause? The evidence for bone health is encouraging. A 12-month RCT showed collagen peptides (5 grams daily) significantly improved bone mineral density in postmenopausal women [7]. They're generally safe and widely available as supplements. They won't replace standard osteoporosis treatments but may offer additional support.

How long before I'd notice effects from peptide therapy? It varies by peptide. Semaglutide can show weight loss within weeks. Collagen peptides take months to affect bone markers. Growth hormone secretagogues like sermorelin typically need 3--6 months. Set realistic expectations with your provider.

Is peptide therapy safe during perimenopause? Safety depends entirely on which peptide, your health history, and medical supervision. FDA-approved peptides like semaglutide have established safety profiles. Research peptides do not. Always discuss with a doctor familiar with both menopause management and peptide therapy.

Can peptides help with hot flashes? Not directly, based on current evidence. Research into CGRP's role in hot flashes may eventually lead to peptide-related treatments, but standard HRT, SSRIs/SNRIs, and the newer NK3 receptor antagonists remain the evidence-based options for vasomotor symptoms.

The Bottom Line {#the-bottom-line}

The honest answer about peptides for menopause: a few have solid evidence, many have interesting preclinical data, and most need more research before anyone can make strong recommendations.

Semaglutide has real clinical data for menopausal weight management. Collagen peptides have good RCT evidence for postmenopausal bone density. Sermorelin and growth hormone secretagogues show promise for body composition and metabolic health, though large menopause-specific trials are missing. Everything else --- BPC-157, MOTS-c, kisspeptin analogs --- is early-stage.

What's clear is that perimenopause and menopause involve more than just declining estrogen. The metabolic, mitochondrial, gut, and neurological shifts that happen alongside hormonal changes are exactly the kind of multi-system problem that peptides, in theory, are well-suited to address. The research just hasn't caught up to the biology yet.

Work with a healthcare provider who understands both menopause and peptide science. Start with what has evidence. Monitor your labs. And stay skeptical of anyone promising that peptides are a menopause cure-all --- they're not. They're one set of tools in what should be a comprehensive approach.

References {#references}

  1. GLP-1 receptor agonists for weight loss for perimenopausal and postmenopausal women: current evidence. PubMed. PMID: 39970049

  2. Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women. Nutrients. PMC5793325

  3. Estrogens and Neuropeptides in Postmenopausal Women: An Update. PMC. PMC3728792

  4. Hurtado MD, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024. PMID: 38446869

  5. Nicolau J, et al. Effectiveness of Low Doses of Semaglutide on Weight Loss and Body Composition Among Women in Their Menopause. Metabolic Syndrome and Related Disorders. PMID: 39761057

  6. GLP-1 Agonists in Perimenopause: Unique Risks and Potential Opportunities. RAND Corporation. 2025. https://www.rand.org/pubs/commentary/2025/08/glp-1-agonists-in-perimenopause-unique-risks-and-potential.html

  7. Konig D, Oesser S, Scharla S, et al. Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women --- A Randomized Controlled Study. Nutrients. 2018;10(1):97. PMID: 29337906

  8. Zdzieblik D, Oesser S, Konig D. Specific Bioactive Collagen Peptides in Osteopenia and Osteoporosis: Long-Term Observation in Postmenopausal Women. J Bone Metab. 2021. PMC8441532

  9. Efficacy of collagen peptide supplementation on bone and muscle health: a meta-analysis. Frontiers in Nutrition. 2025. PMC12488437

  10. Efficacy of hexapeptide-7 on menopausal skin. PubMed. PMID: 20120425

  11. Oral Collagen Peptides and Vulvovaginal Radiofrequency Therapy for Genitourinary Syndrome of Menopause. J Clin Med. 2025. PMID: 40507418

  12. Walker RF. Sermorelin: A better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006. PMC2699646

  13. George JT, et al. Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men. J Clin Endocrinol Metab. 2011. PMC3380939

  14. Sikiric P, et al. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol. 2017. PMC5333585

  15. Lu H, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023. PMC9854231

  16. Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021. https://www.nature.com/articles/s41467-020-20790-0

  17. Calcitonin gene-related peptide and menopause. PMC. PMC3139267