Review findings

nt with hCG significantly decreased tissue loss, cystic degeneration and PV+ interneuron loss; reduced microglial Iba1 immunoreactivity Preclinical evidence of anti-inflammatory/neuroprotective effects; further work needed for translational relevance hCG-derived peptide (EA-230) — immunomodulatory/renal protection van Groenendael et al., 2019 Review / translational studies summarizing preclinical and Phase I human work Phase I healthy volunteer studies cited (small n) EA-230 (hCG-derived tetrapeptide) intravenous formulations in early human studies Placebo (in early trials) Immunomodulation biomarkers; renal function endpoints in models/humans Preclinical models: anti-inflammatory and renal-protective effects; early human phase I studies demonstrated modulation of immune markers and safet...

1500-5000 IU (fertility protocols) Frequency Every other day or 2-3 times per week Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols 💊 Administration Route SC Schedule Every other day or 2-3 times per week Timing No specific time of day; maintain consistent schedule ✓ Rotate injection sites 📅 Cycle Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols Repeatable Yes Preparation & Storage Diluent: Bacteriostatic water ⚗️ Suggested Bloodwork ( 6 tests) Total and free testosterone When: Baseline Why: Baseline androgen status Estradiol (sensitive assay) When: Baseline Why: HCG increases intratesticular aromatization LH and FSH When: Baseline Why: Baseline gonadotropin levels CBC When: Baseline Why: Baseline hematology (HCG can increase erythropoiesis) Semen analysis (if fertility goal) When: Baseline Why: Baseline fertility assessment Estradiol When: 4-6 weeks Why: HCG can significantly raise estradiol; may need AI if elevated 💡 Key Considerations → IM injection yields higher Cmax and AUC than SC, especially in obese individuals → Higher doses (1500-5000 IU) are used for fertility induction combined with FSH/HMG but increase estradiol conversion → Contraindication: Contraindicated in androgen-dependent neoplasms (prostate cancer), precocious puberty, and pregnancy Subscribe to unlock this conte

Protocol Wiki February 13, 2026 Alprostadil Gonadorelin HCG + 2 more Research Review 12 min read Reproductive Health Peptides: A Research Roundup Peptides for reproductive health — kisspeptin, gonadorelin, HCG, HMG, triptorelin, and PT-141 — with evidence levels and clinical status.

Group B: hCG 250 IU twice weekly 6 wks FSH+hCG vs hCG alone Successful testicular descent to mid/low scrotal position at 12 wks Descent: Group A 6/18 testes;

Peptide Protocol Wiki February 13, 2026 Gonadorelin HCG HMG + 2 more Guide 14 min read Peptides for Men's Sexual Health: PT-141, Kisspeptin, and Emerging Options Guide to peptides researched for male sexual health including PT-141, kisspeptin, gonadorelin, HCG, alprostadil, and oxytocin with evidence levels.

ed) 5 trials (total ~596 women across included studies) Various hCG regimens used prophylactically in early pregnancy Placebo / no treatment / other agents Live birth / pregnancy loss Evidence mixed; some pooled analyses suggested possible reduction in miscarriage in small trials but heterogeneity and trial quality limit conclusions Trials varied; overall evidence insufficient to recommend routine hCG prophylaxis Threatened miscarriage — therapeutic hCG Qureshi et al., 2005 Prospective, double-blind, randomized, placebo-controlled trial (Early Pregnancy Unit) 183 women (hCG 87 vs placebo 96) IM hCG (Profasi) weekly until 14 wks (median ~7 injections) Placebo (saline) Miscarriage rate (primary) No difference: miscarriages ~11% placebo vs 12% hCG;

pective cohort) Patients with benign/malignant ovarian tumors (cohort detailed in paper) Measured serum hCG by ELISA;

Report an Error Compare HCG with Other Peptides HCG vs HMG HCG and HMG serve complementary rather than competing roles in reproductive medicine.

HCG: Fertility and Testosterone Research Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?

Evidence does not support hCG for weight loss and does not show benefit for threatened miscarriage; prophylaxis in recurrent miscarriage remains unproven.

Where to Find HCG Compare all vendor prices → Research-grade suppliers verified by our scoring methodology.

sensus conclusion: Across randomized trials, the 1995 meta-analysis, and later reviews, HCG does not confer clinically meaningful weight-loss benefit beyond the accompanying VLCD.

Restore access No thanks, continue reading Related Reading Peptide Gonadorelin GnRH hypothalamic peptide Peptide HMG human menopausal gonadotropin Peptide Kisspeptin reproductive hormone peptide How HCG works at the cellular level Overview of HCG benefits and applications Scientific Details Molecular Formula Glycoprotein heterodimer (~25.7 kDa peptide + ~10-15 kDa glycans) Molecular Weight 36700 Da CAS Number 9002-61-3 Sequence Heterodimer: alpha subunit (92 aa) + beta subunit (145 aa), 237 aa total What is HCG? # HCG is a peptide that has been studied in preclinical and clinical research models for its potential therapeutic properties.

Professional bariatric societies have issued position statements advising against the Simeons/HCG method for weight loss due to lack of efficacy and safety concerns.

The evidence base for HCG as a weight-loss aid is extensive enough to conclude that it is ineffective beyond the effects of a severe VLCD, with consistent results across RCTs and a criteria-based meta-analysis.

Ligand-specific contacts at the ECD/hinge and hormone glycosylation underlie biased signaling differences between hCG and LH (casariniUnknownyearadvancearticle pages 17-18).

Butler & Cole (2016) Narrative review of half‑century evidence and associated risks of HCG‑supplemented diets.

In primary human granulosa cells, LH elicits stronger and more sustained ERK1/2 and AKT phosphorylation than hCG at equipotent doses, consistent with a proliferative/survival bias of LH versus a steroidogenic bias of hCG.

base for HCG consists primarily of preclinical studies.

Angiogenic signaling and molecular targets • hCG promotes angiogenesis in the corpus luteum and placenta through multiple pathways.

What are the benefits of HCG?

Mechanistic distinction from LH (biased agonism at LHCGR) • Although hCG and LH share LHCGR, they stabilize distinct receptor conformations and produce different signaling ensembles.

Receptor active state, G protein recruitment, possible dimer/oligomer formation hCG structural features (CTP, glycosylation) and ECD contacts bias receptor conformation and signaling vs LH (simoniUnknownyearoggettoendocrinerevi...

Cell proliferation/survival (anti‑apoptotic signals), modulation of steroidogenic gene expression (StAR, aromatase regulation) LH tends to elicit stronger ERK/AKT activation in granulosa cells, whereas hCG is more steroidogenic via cAMP; both pathways necessary for full StA...

StAR phosphorylation/expression) EGFR transactivation mediates an early MAPK-dependent steroidogenic component; evidence for MMP-independent EGFR activation in Leydig models Angiogenesis targets (VEGF / EG-VEGF / PROKR1/2) LHCGR → cAMP/CRE and other kinases; hCG (and hCG‑H) also acts via alternate receptors (e.g., TGFβRII) to promote angiogenesis Upregulation of EG-VEGF (prokineticin‑1) and PROKR1/2 via cAMP/CRE elements; hCG can increase VEGF via NF‑κB/HIF-linked routes and direct angiogeni...

In a multi-center, single-arm phase III trial in adult men with hypogonadotropic hypogonadism who remained azoospermic after 16 weeks of hCG alone, adding corifollitropin alfa (150 µg every 2 weeks) to continued hCG twice-weekly (1,500 IU, uptitrated to 3,000 IU in 7/18) for 52 weeks increased mean testicular volume from 8.6 to 17.8 mL and induced spermatogenesis ≥1×10^6/mL in 14/18 (77.8%); adverse events were generally mild (estradiol increase n=3; testosterone changes n=4).

A randomized, double-blind, double-dummy trial (n=84 cycles) showed recombinant hCG and urinary hCG were equivalent for final oocyte maturation, with similar oocyte yield, maturation, fertilization, and pregnancy outcomes; safety was comparable.

A criteria-based meta-analysis of randomized trials of the Simeons protocol (very-low-calorie diet plus daily low-dose hCG injections) found no added effect of hCG on weight loss, fat redistribution, hunger, or well-being versus placebo or diet alone; weight loss was attributable to the calorie restriction, not hCG.

ve actions (preprint; further validation warranted). hCG-derived peptide (EA-230).

Embedded study summary table Indication Study (Year) (citation) Design / Setting n hCG regimen (dose / role) Comparator Primary endpoint(s) Main efficacy outcome Key safety findings Hypogonadotropic hypogonadism (spermatogenesis) Nieschlag et al., 2017 Phase III, multi-centre open-label (hCG + corifollitropin alfa) 18 in combined phase hCG twice-weekly (1500 IU; uptitrated to 3000 IU in 7/18) plus corifollitropin alfa 150 µg q2w No placebo (single-arm after hCG pretreatment) Increase in testicular volume; induction of spermatogenesis (≥1×10^6/mL) Testicular volume ↑ 8.6 → 17.8 mL;

Protocol Wiki February 13, 2026 Alprostadil Gonadorelin HCG + 2 more Research Review 12 min read Reproductive Health Peptides: A Research Roundup Peptides for reproductive health — kisspeptin, gonadorelin, HCG, HMG, triptorelin, and PT-141 — with evidence levels and clinical status.

Peptide Protocol Wiki February 10, 2026 Semaglutide Ipamorelin Sermorelin + 2 more You Might Also Like Related content you may find interesting Peptide Reproductive HMG Peptide Reproductive Gonadorelin Peptide Reproductive MVT-602 Peptide Reproductive Triptorelin Table of Contents What is HCG?

1500-5000 IU (fertility protocols) Frequency Every other day or 2-3 times per week Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols 💊 Administration Route SC Schedule Every other day or 2-3 times per week Timing No specific time of day; maintain consistent schedule ✓ Rotate injection sites 📅 Cycle Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols Repeatable Yes Preparation & Storage Diluent: Bacteriostatic water ⚗️ Suggested Bloodwork ( 6 tests) Total and free testosterone When: Baseline Why: Baseline androgen status Estradiol (sensitive assay) When: Baseline Why: HCG increases intratesticular aromatization LH and FSH When: Baseline Why: Baseline gonadotropin levels CBC When: Baseline Why: Baseline hematology (HCG can increase erythropoiesis) Semen analysis (if fertility goal) When: Baseline Why: Baseline fertility assessment Estradiol When: 4-6 weeks Why: HCG can significantly raise estradiol; may need AI if elevated 💡 Key Considerations → IM injection yields higher Cmax and AUC than SC, especially in obese individuals → Higher doses (1500-5000 IU) are used for fertility induction combined with FSH/HMG but increase estradiol conversion → Contraindication: Contraindicated in androgen-dependent neoplasms (prostate cancer), precocious puberty, and pregnancy Subscribe to unlock this conte

dose: 5000 IU · cycle: Cycle · route: IM · frequency: Every other day · reconstitution: Bacteriostatic

14/18 (77.8%) achieved ≥1×10^6/mL sperm at 52 wk Generally well tolerated; ↑ estradiol (n=3); testosterone changes reported (n=4) Preservation of spermatogenesis during TRT Hsieh et al., 2013 Retrospective clinical series (andrology clinics) 26 men TRT (injectable or topical) + IM hCG 500 IU every other day No-hCG TRT historical controls (retrospective) Maintenance of semen parameters / fertility during TRT No patient became azoospermic; semen parameters preserved;

dose: 500 IU · route: topical · frequency: every other day

In a multi-center, single-arm phase III trial in adult men with hypogonadotropic hypogonadism who remained azoospermic after 16 weeks of hCG alone, adding corifollitropin alfa (150 µg every 2 weeks) to continued hCG twice-weekly (1,500 IU, uptitrated to 3,000 IU in 7/18) for 52 weeks increased mean testicular volume from 8.6 to 17.8 mL and induced spermatogenesis ≥1×10^6/mL in 14/18 (77.8%); adverse events were generally mild (estradiol increase n=3; testosterone changes n=4).

dose: 150 µg · duration: for 52 weeks · frequency: weekly

In threatened miscarriage with a viable fetus, a prospective double-blind RCT (n=183) using weekly IM hCG 5,000 IU until 14 weeks showed no difference in miscarriage (11% placebo vs 12% hCG;

dose: 000 IU · route: IM · frequency: weekly

For threatened miscarriage RCTs, no excess adverse events were observed with weekly 5,000 IU IM hCG to 14 weeks.

dose: 000 IU · route: IM · frequency: weekly

A retrospective series of 26 hypogonadal men on testosterone replacement who received concomitant intramuscular hCG 500 IU every other day reported preserved semen parameters over up to 18 months, zero azoospermia, and 9/26 partner pregnancies; serum testosterone rose from 207 to 1,056 ng/dL; no major adverse events reported.

dose: 500 IU · route: intramuscular · frequency: every other day

A double-blind, placebo-controlled RCT in 22 boys compared FSH+hCG (FSH 150 IU twice weekly for 2 weeks, then FSH 150 IU + hCG 250 IU twice weekly for 4 weeks) versus hCG alone (hCG 250 IU twice weekly for 6 weeks).

dose: 150 IU · duration: for 2 weeks · frequency: twice weekly

Group B: hCG 250 IU twice weekly 6 wks FSH+hCG vs hCG alone Successful testicular descent to mid/low scrotal position at 12 wks Descent: Group A 6/18 testes;

dose: 250 IU · frequency: twice weekly

9/26 reported partner pregnancy during follow-up No major adverse events reported; small cohort, limited follow-up Cryptorchidism (testicular descent) Hoorweg-Nijman et al., 1994 Double-blind, placebo-controlled RCT (paediatric) 22 boys (total testes: Group A 18, Group B 10) Group A: FSH 150 IU twice weekly 2 wks → FSH 150 + hCG 250 IU tw

dose: 150 IU · frequency: twice weekly

Embedded study summary table Indication Study (Year) (citation) Design / Setting n hCG regimen (dose / role) Comparator Primary endpoint(s) Main efficacy outcome Key safety findings Hypogonadotropic hypogonadism (spermatogenesis) Nieschlag et al., 2017 Phase III, multi-centre open-label (hCG + corifollitropin alfa) 18 in combined phase hCG twice-weekly (1500 IU; uptitrated to 3000 IU in 7/18) plus corifollitropin alfa 150 µg q2w No placebo (single-arm after hCG pretreatment) Increase in testicular volume; induction of spermatogenesis (≥1×10^6/mL) Testicular volume ↑ 8.6 → 17.8 mL;

dose: 1500 IU · frequency: weekly

Research Evidence Quality # Overview of the evidence base Extent/quality: The most comprehensive formal review is a criteria-based meta-analysis of the Simeons HCG protocol (125 IU daily plus ~500 kcal/day for 3.5–6 weeks) that examined controlled trials from 1966–1993.

dose: 125 IU · frequency: daily

support, and ovulation induction 💉 Dosing Amount 250-500 IU per injection (TRT adjunct);

dose: 500 IU

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HCG: Fertility and Testosterone Research Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?

Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About HCG 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides HCG Reproductive Health Hormonal Health approved HCG Also known as: Human Chorionic Gonadotropin, hCG, Pregnyl, Novarel, Ovidrel Compare with 1 peptide Research compiled by Peptide Protocol Wiki 📅 Updated February 1, 2026 Citations Verified TL;DR HCG (Human Chorionic Gonadotropin) is a glycoprotein hormone composed of alpha and beta subunits.

Browse all reproductive peptides → Table of Contents 📌 TL;DR • FDA-approved for multiple reproductive indications • Stimulates testicular testosterone production in males • Triggers ovulation in fertility treatment protocols • Maintains Leydig cell function during testosterone therapy Community-Reported Side Effects Anecdotal ? 📋 Protocol Quick-Reference Testicular function preservation during TRT, fertility

A retrospective series of 26 hypogonadal men on testosterone replacement who received concomitant intramuscular hCG 500 IU every other day reported preserved semen parameters over up to 18 months, zero azoospermia, and 9/26 partner pregnancies; serum testosterone rose from 207 to 1,056 ng/dL; no major adverse events reported.

In a multi-center, single-arm phase III trial in adult men with hypogonadotropic hypogonadism who remained azoospermic after 16 weeks of hCG alone, adding corifollitropin alfa (150 µg every 2 weeks) to continued hCG twice-weekly (1,500 IU, uptitrated to 3,000 IU in 7/18) for 52 weeks increased mean testicular volume from 8.6 to 17.8 mL and induced spermatogenesis ≥1×10^6/mL in 14/18 (77.8%); adverse events were generally mild (estradiol increase n=3; testosterone changes n=4).

9/26 reported partner pregnancy during follow-up No major adverse events reported; small cohort, limited follow-up Cryptorchidism (testicular descent) Hoorweg-Nijman et al., 1994 Double-blind, placebo-controlled RCT (paediatric) 22 boys (total testes: Group A 18, Group B 10) Group A: FSH 150 IU twice weekly 2 wks → FSH 150 + hCG 250 IU tw

Group B 6/10 testes; no significant benefit of adding FSH No serious adverse events; many nonresponders had anatomical abnormalities at surgery Assisted reproduction — oocyte maturation trigger (recombinant vs urinary hCG) Driscoll et al., 2000 Prospective, randomized, double-blind, double-dummy multi-centre trial 84 receiving hCG (r-hCG n=44; u-hCG n=40) Single trigger for final oocyte maturation: recombinant hCG vs urinary hCG (standard clinical dosing) r-hCG vs u-hCG Oocyte maturation, MII oocyte yield, fertilization r-hCG and u-hCG produced equivalent outcomes (oocyte yield/maturation/fertilization) No major safety differences reported between r-hCG and u-hCG Assisted reproduction — dual trigger (GnRH-agonist + hCG) Haas et al., 2020 Single-centre, randomized, double-blind RCT (normal responders) 155 randomized Dual trigger (GnRH-agonist + hCG) vs hCG alone at trigger hCG alone Number of oocytes/MII oocytes, blastocyst yield, clinical pregnancy, live birth Dual trigger ↑ eggs retrieved (13.4 vs 11.1), MII oocytes (10.3 vs 8.6), total & top-quality blastocysts, clinical pregnancy 46.1% vs 24.3%; live b...

Across reproductive indications, hCG is generally well tolerated; adverse effects include estradiol-related symptoms and, rarely, thromboembolic events reported anecdotally in weight-loss misuse settings.

For threatened miscarriage RCTs, no excess adverse events were observed with weekly 5,000 IU IM hCG to 14 weeks.

Safety, adverse events, and regulatory/professional positions Adverse events: Reports associated with HCG diet use include venous thromboembolism (deep vein thrombosis/pulmonary embolism), with at least one case assessed as “probable” by the Naranjo causality scale; other reported effects include headaches, mood changes (anxiety, irritability, depression), insomnia, pruritus, hypotension, hypoglycemia, constipation, delayed menses, and laboratory changes likely related to semistarvation (decreases in WBC, hematocrit, total protein, lipids; increased uric acid).

In 2011, FDA/FTC sent warning letters to firms marketing OTC/homeopathic HCG for weight loss, noting these were unapproved drugs with unsupported claims and that HCG is not recognized in the

Source (year) Design / Scope Efficacy vs. calorie restriction Safety / adverse events & regulatory notes Key limitations / criticisms Lijesen et al.

ort; lists multiple reported adverse events (mood changes, headaches, metabolic ch...

PMID: 23440828): The study showed review of 5 trials The study showed review of 5 trials ; pooled data suggested possible reduction in miscarriage but effect lost after excluding lower quality trials; evidence insufficient to recommend routine hCG prophylaxis Related Reading # HCG research studies and evidence HCG dosing protocols HCG side effects profile Gonadorelin research guide HMG research guide Stay current on HCG research We summarize new studies, safety updates, and dosing insights — delivered biweekly.

What are the side effects of HCG?

Reported side effects of HCG include ovarian hyperstimulation syndrome, headache, gynecomastia, acne.

Most reported side effects are mild and transient.

Consult the detailed side effects profile for full information.

A Cochrane review of randomized trials (five studies; ~596 women) assessing prophylactic hCG in women with recurrent miscarriage found heterogeneous regimens and risk of bias.

9/26 reported partner pregnancy during follow-up No major adverse events reported; small cohort, limited follow-up Cryptorchidism (testicular descent) Hoorweg-Nijman et al., 1994 Double-blind, placebo-controlled RCT (paediatric) 22 boys (total testes: Group A 18, Group B 10) Group A: FSH 150 IU twice weekly 2 wks → FSH 150 + hCG 250 IU tw

1500-5000 IU (fertility protocols) Frequency Every other day or 2-3 times per week Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols 💊 Administration Route SC Schedule Every other day or 2-3 times per week Timing No specific time of day; maintain consistent schedule ✓ Rotate injection sites 📅 Cycle Duration Ongoing while on TRT; or 6-12 weeks for PCT/fertility protocols Repeatable Yes Preparation & Storage Diluent: Bacteriostatic water ⚗️ Suggested Bloodwork ( 6 tests) Total and free testosterone When: Baseline Why: Baseline androgen status Estradiol (sensitive assay) When: Baseline Why: HCG increases intratesticular aromatization LH and FSH When: Baseline Why: Baseline gonadotropin levels CBC When: Baseline Why: Baseline hematology (HCG can increase erythropoiesis) Semen analysis (if fertility goal) When: Baseline Why: Baseline fertility assessment Estradiol When: 4-6 weeks Why: HCG can significantly raise estradiol; may need AI if elevated 💡 Key Considerations → IM injection yields higher Cmax and AUC than SC, especially in obese individuals → Higher doses (1500-5000 IU) are used for fertility induction combined with FSH/HMG but increase estradiol conversion → Contraindication: Contraindicated in androgen-dependent neoplasms (prostate cancer), precocious puberty, and pregnancy Subscribe to unlock this conte

Peptide Protocol Wiki February 13, 2026 Gonadorelin HCG HMG + 2 more Guide 14 min read Peptides for Men's Sexual Health: PT-141, Kisspeptin, and Emerging Options Guide to peptides researched for male sexual health including PT-141, kisspeptin, gonadorelin, HCG, alprostadil, and oxytocin with evidence levels.

Protocol Wiki February 13, 2026 Alprostadil Gonadorelin HCG + 2 more Research Review 12 min read Reproductive Health Peptides: A Research Roundup Peptides for reproductive health — kisspeptin, gonadorelin, HCG, HMG, triptorelin, and PT-141 — with evidence levels and clinical status.

Peptide Protocol Wiki February 10, 2026 Semaglutide Ipamorelin Sermorelin + 2 more You Might Also Like Related content you may find interesting Peptide Reproductive HMG Peptide Reproductive Gonadorelin Peptide Reproductive MVT-602 Peptide Reproductive Triptorelin Table of Contents What is HCG?