Comparison
Clomiphene vs Low-Dose Naltrexone
Side-by-side of Clomiphene and Low-Dose Naltrexone. 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.
Low-Dose Naltrexone
Low dose naltrexone at 1.5 to 4.5 mg, one-tenth the 50 mg addiction dose. Compounded Rx. Small trials in fibromyalgia, Crohn's, Hashimoto's.
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)
Low-Dose Naltrexone
- •Off-label use at 1.5 to 4.5 mg, roughly one-tenth the FDA-approved 50 mg addiction-treatment dose
- •Proposed mechanisms include brief opioid receptor blockade triggering rebound endogenous opioid release, plus TLR4 antagonism
- •Compounded prescription only; insurance rarely covers; cash prices 20 to 80 USD per month
- •Younger 2013 reported ~30% pain reduction in fibromyalgia at 4.5 mg in a small crossover trial
- •Smith 2011 reported endoscopic improvement in active Crohn's disease (n=40 placebo-controlled)
- •Vivid dreams affect 20 to 40% in first 2 weeks; manageable by switching to morning dosing
Side-by-side
| Attribute | Clomiphene | Low-Dose Naltrexone |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | Clomid, clomiphene citrate, Serophene, enclomiphene | LDN, naltrexone (low dose) |
| Half-life (hr) ↗ | 168 | 4 |
| Typical dose (mg) ↗ | 25 | 4.5 |
| Dosing frequency | 5-day pulse cycle days 5 to 9 (women); daily or every other day (men, off-label) | once daily, typically at bedtime |
| Routes | oral | oral |
| Onset (hr) | 6 | 1 |
| Peak (hr) | 7 | 1.5 |
| Molecular weight | 405.96 | 341.4 |
| Molecular formula | C26H28ClNO | C20H23NO4 |
| Mechanism | Selective estrogen receptor modulator that antagonizes estrogen at the hypothalamus and pituitary, increasing GnRH and gonadotropin output, which drives gonadal steroidogenesis. | Brief mu-opioid receptor antagonism proposed to trigger compensatory upregulation of endogenous opioids; secondary TLR4 antagonism on microglia and immune cells contributes to anti-inflammatory effect. |
| Legal status | Prescription only (FDA approved for ovulation induction; off-label in men) | Off-label compounded prescription (naltrexone is FDA approved for opioid and alcohol use disorder at 50 mg) |
| WADA status | banned | allowed |
| DEA / Rx | Rx only (not a controlled substance) | Rx only (not a controlled substance) |
| Pregnancy | Category X; contraindicated in pregnancy | Insufficient data; not routinely recommended |
| CAS | 911-45-5 | 16590-41-3 |
| PubChem CID | 1548953 | 5360515 |
| Wikidata | Q416785 | Q426444 |
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)
Low-Dose Naltrexone
Common side effects
- vivid dreams
- sleep disruption
- headache
- mild GI upset
- fatigue (early)
Contraindications
- concurrent opioid use
- acute hepatitis or liver failure
- opioid dependence
- pregnancy (insufficient data)
Interactions
- opioid analgesics (oxycodone, morphine, codeine): blocks analgesic effect; precipitates withdrawal in dependent users(major)
- tramadol: blocks opioid component of analgesia(major)
- thyroid hormone replacement: may alter dose requirements after immune modulation; monitor TSH(minor)
Which Should You Take?
Clomiphene and Low-Dose Naltrexone 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 immune support, pick Low-Dose Naltrexone.
- → If your priority is pain modulation, pick Low-Dose Naltrexone.
Edge case: Clomiphene is contraindicated in pregnancy; Low-Dose Naltrexone is the safer pick if that applies.
Default choice: either is defensible. Clomiphene edges out on goal breadth + legal accessibility; Low-Dose Naltrexone 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 Low-Dose Naltrexone?
Clomiphene and Low-Dose Naltrexone 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 Low-Dose Naltrexone?
Clomiphene half-life is 168 hours; Low-Dose Naltrexone half-life is 4 hours.
Can you stack Clomiphene with Low-Dose Naltrexone?
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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