Comparison
Clomiphene vs Metformin
Side-by-side of Clomiphene and Metformin. 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.
Metformin
Metformin for longevity: biguanide mechanism of action, TAME trial status, anti-aging dosage, weight loss data, life extension evidence in non-diabetics.
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)
Metformin
- •Reduces HbA1c by ~1.0 to 1.5 percentage points in type 2 diabetes; first-line agent in major guidelines
- •DPP trial: 31% reduction in T2DM incidence in adults with prediabetes over 2.8 years
- •Suppresses hepatic gluconeogenesis via AMPK activation and complex I inhibition
- •Long-term use depletes B12; annual monitoring recommended after year 2
- •Lifespan extension in non-diabetic humans is not established; TAME trial pending
- •MASTERS trial reported blunted resistance-training hypertrophy in older adults
Side-by-side
| Attribute | Clomiphene | Metformin |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | Clomid, clomiphene citrate, Serophene, enclomiphene | Glucophage, Fortamet, Glumetza, dimethylbiguanide |
| Half-life (hr) ↗ | 168 | 6 |
| Typical dose (mg) ↗ | 25 | 1500 |
| Dosing frequency | 5-day pulse cycle days 5 to 9 (women); daily or every other day (men, off-label) | 1 to 3 times daily with meals; XR once daily |
| Routes | oral | oral |
| Onset (hr) | 6 | 1 |
| Peak (hr) | 7 | 2.5 |
| Molecular weight | 405.96 | 129.16 |
| Molecular formula | C26H28ClNO | C4H11N5 |
| Mechanism | Selective estrogen receptor modulator that antagonizes estrogen at the hypothalamus and pituitary, increasing GnRH and gonadotropin output, which drives gonadal steroidogenesis. | Suppresses hepatic gluconeogenesis primarily via AMPK activation and complex I inhibition; modestly improves peripheral insulin sensitivity and shifts gut microbiome composition. |
| Legal status | Prescription only (FDA approved for ovulation induction; off-label in men) | Prescription only (FDA approved for type 2 diabetes 1994) |
| WADA status | banned | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Category X; contraindicated in pregnancy | Category B; used in gestational diabetes and PCOS per current guidance |
| CAS | 911-45-5 | 657-24-9 |
| PubChem CID | 1548953 | 4091 |
| Wikidata | Q416785 | Q19484 |
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)
Metformin
Common side effects
- nausea
- diarrhea
- abdominal discomfort
- metallic taste
- decreased appetite
- B12 depletion (long-term)
Contraindications
- eGFR below 30 mL/min/1.73m2
- acute or chronic metabolic acidosis
- severe hepatic impairment
- acute heart failure
- iodinated contrast within 48 hours
Interactions
- iodinated contrast media: renal injury risk; hold 48 hours peri-imaging(major)
- alcohol (heavy use): elevated lactic acidosis risk(major)
- cimetidine: raises metformin plasma levels via OCT2 inhibition(moderate)
- insulin and sulfonylureas: additive hypoglycemia risk in combination(moderate)
- dolutegravir: raises metformin exposure via OCT2(moderate)
Which Should You Take?
Clomiphene and Metformin score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is hormonal optimization, pick Clomiphene.
- → If your priority is fertility, pick Clomiphene.
- → If your priority is metabolic health and glucose control, pick Metformin.
- → If your priority is healthspan extension, pick Metformin.
Edge case: Clomiphene is contraindicated in pregnancy; Metformin is the safer pick if that applies.
Default choice: either is defensible. Clomiphene edges out on goal breadth + legal accessibility; Metformin is the right call if your priority sits in the goals listed 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 Metformin?
Clomiphene and Metformin differ in category (pharmaceutical vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Clomiphene or Metformin?
Clomiphene half-life is 168 hours; Metformin half-life is 6 hours.
Can you stack Clomiphene with Metformin?
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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