Comparison
Clomiphene vs MOTS-c
Side-by-side of Clomiphene and MOTS-c. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Clomiphene
Clomiphene citrate raises LH/FSH and endogenous testosterone in men. SERM TRT alternative, 25 to 50 mg, fertility preserved, visual side effects flagged.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Effects at a glance
Clomiphene
- •SERM that blocks estrogen-receptor negative feedback at the hypothalamus, raising LH and FSH
- •FDA approved 1967 for ovulation induction in anovulatory women at 50 to 100 mg cycle days 5 to 9
- •Off-label in men at 12.5 to 25 mg daily raises endogenous testosterone while preserving fertility
- •Enclomiphene (trans-isomer) is preferred for male use; cleaner PK and less estrogenic side effect burden
- •Visual disturbances occur in ~1 to 2% of users; persistent symptoms warrant immediate cessation
- •Letrozole has displaced clomiphene as first-line ovulation induction in PCOS (Legro 2014)
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Side-by-side
| Attribute | Clomiphene | MOTS-c |
|---|---|---|
| Category | pharmaceutical | peptide |
| Also known as | Clomid, clomiphene citrate, Serophene, enclomiphene | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 168 | 0.5 |
| Typical dose (mg) ↗ | 25 | 5 |
| Dosing frequency | 5-day pulse cycle days 5 to 9 (women); daily or every other day (men, off-label) | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 6 | 1 |
| Peak (hr) | 7 | 4 |
| Molecular weight | 405.96 | 1880.18 |
| Molecular formula | C26H28ClNO | C82H132N22O25S2 |
| Mechanism | Selective estrogen receptor modulator that antagonizes estrogen at the hypothalamus and pituitary, increasing GnRH and gonadotropin output, which drives gonadal steroidogenesis. | Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. |
| Legal status | Prescription only (FDA approved for ovulation induction; off-label in men) | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | banned | unknown |
| DEA / Rx | Rx only (not a controlled substance) | Not scheduled (research chemical) |
| Pregnancy | Category X; contraindicated in pregnancy | Insufficient data; not recommended |
| CAS | 911-45-5 | 1627580-64-6 |
| PubChem CID | 1548953 | 139599184 |
| Wikidata | Q416785 | Q24832108 |
Safety profile
Clomiphene
Common side effects
- hot flushes
- mood changes
- abdominal discomfort
- breast tenderness
- visual disturbances (rare)
- headache
Contraindications
- pregnancy
- active liver disease
- ovarian cysts (not PCOS-related)
- uncontrolled thyroid or adrenal disorder
- abnormal uterine bleeding of undetermined origin
- hormone-sensitive cancer
Interactions
- tamoxifen: competing SERM activity; not used together(moderate)
- ospemifene: competing SERM activity(moderate)
- anastrozole: additive estrogen reduction; sometimes combined in male protocols(minor)
- TRT (exogenous testosterone): TRT suppresses HPT axis that clomiphene targets; do not combine(moderate)
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)
Which Should You Take?
Clomiphene comes out ahead for most readers on the criteria we weight: 2 catalogued goals, prescription-only, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is hormonal optimization, pick Clomiphene.
- → If your priority is fertility, pick Clomiphene.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
Edge case: If you cannot self-administer injections, Clomiphene is the only oral option in this pair.
Default choice: Clomiphene. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Clomiphene and MOTS-c?
Clomiphene and MOTS-c differ in category (pharmaceutical vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Clomiphene or MOTS-c?
Clomiphene half-life is 168 hours; MOTS-c half-life is 0.5 hours.
Can you stack Clomiphene with MOTS-c?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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