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[TRT · Comparison]

hCG vs enclomiphene: how do they differ?

Mechanism · FDA status · Trials

Short answer: hCG is an FDA-approved injection that acts like LH directly on the testes.1 Enclomiphene is an oral SERM that blocks estrogen feedback at the brain so the pituitary releases more LH and FSH; it is not FDA approved (FDA declined it in 2015).2 In trials, enclomiphene raised testosterone while keeping sperm counts, unlike testosterone gel.3

How do hCG and enclomiphene compare side by side?

hCG from the Novarel and Pregnyl labels; enclomiphene from published trials and FDA records.
hCG (Novarel, Pregnyl)Enclomiphene
MechanismActs on the LH receptor in the testesSelective estrogen receptor modulator; raises the body's own LH and FSH4
Approval statusFDA approved, including for selected hypogonadotropic hypogonadism in males1Not FDA approved; complete response letter December 20152. FDA 503A Category 1 (under evaluation)5
Dosing scheduleLabel (male hypogonadotropic hypogonadism): 500 to 1,000 USP units 3 times a week for 3 weeks, then twice a week for 3 weeks; or 4,000 units 3 times a week for 6 to 9 months, then 2,000 units 3 times a week for 3 months1Studied: 12.5 or 25 mg by mouth daily in phase 3 trials6
RouteInjection into muscle only, per the label7By mouth
Half-lifeNot stated on the labels. Dose Track uses about 29 hours, from the Ovidrel label (recombinant hCG, under the skin)8Sources conflict; a single-dose study could not estimate a terminal half-life9
Time to peak (Tmax)Not stated on the Novarel or Pregnyl labelsAbout 3 hours after a clomiphene dose9
Effect on spermNot addressed in the label dosing sectionsSperm concentration kept in the normal range vs a marked fall on testosterone gel3
Strengths5,000 and 10,000 unit vials (powder)No approved product
Notable label warningsLabel statement (in capitals) that hCG is not effective for obesity; precocious puberty when treating cryptorchidism; ovarian hyperstimulation in women1No label. In phase 3, 14.2% on drug vs 2.6% to 4.3% on placebo had a 50% or larger drop in sperm concentration610

Reviewed . Half-life figures are shown only where the value Dose Track uses agrees with the cited source.

Why are both used alongside or instead of TRT?

Testosterone therapy suppresses the brain's LH and FSH signals, which can lower sperm production. hCG replaces the LH signal directly. Enclomiphene works one step earlier, raising the body's own LH and FSH. Both are discussed for men who want to keep testicular function, but only hCG is FDA approved, and its approved male use is hypogonadotropic hypogonadism.1

What did the enclomiphene trials report?

  • Phase 2 (2013): after 6 weeks, total testosterone was 604 ± 160 ng/dL on 25 mg vs 500 ± 278 ng/dL on testosterone gel.11
  • Phase 3 vs testosterone gel (2016): enclomiphene kept sperm concentration in the normal range, while the gel caused a marked fall.3
  • Phase 3 vs placebo (ZA-301, ZA-302): about 79% to 81% reached normal testosterone at 12 weeks.610

FDA declined to approve it in 2015, saying the phase 3 design was no longer adequate to show clinical benefit.2

This page summarizes labels and published studies. It is not personalized medical advice; confirm any dose or change with your prescriber.
Testosterone cypionate vs enanthate: is there a real difference?Same dose range, different oil, similar half-life Weekly vs twice-weekly TRT injections: does splitting the dose help?Half-life math, guideline, hematocrit data

Frequently asked questions

Is enclomiphene FDA approved?+
No. FDA issued a complete response letter in December 2015. As of 2026 it is on FDA's Category 1 list of bulk substances under evaluation for compounding.25
What is the difference between hCG and enclomiphene?+
hCG is an injection that acts like LH directly on the testes. Enclomiphene is a pill that blocks estrogen feedback so the pituitary releases more of the body's own LH and FSH.
What does the hCG label say about dosing in men?+
For hypogonadotropic hypogonadism, the Novarel label lists 500 to 1,000 USP units 3 times a week for 3 weeks then twice a week for 3 weeks, or 4,000 units 3 times a week for 6 to 9 months then 2,000 units 3 times a week for 3 months, injected into muscle.1
Can I track hCG in Dose Track?+
Yes. hCG is built in with IU-based reconstitution math, and you can log it next to testosterone and any oral medication.

Sources

  1. Novarel (chorionic gonadotropin for injection) prescribing information. DailyMed.
  2. Repros Therapeutics. Repros receives complete response letter for enclomiphene. News release filed with the SEC, December 1, 2015.
  3. Kim ED, et al. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: two phase 3 trials. BJU Int. 2016.
  4. Wiehle RD, et al. Enclomiphene citrate stimulates serum testosterone in men with low testosterone while maintaining sperm counts (ZA-203). Fertil Steril. 2014.
  5. FDA. 503A bulk drug substances under evaluation (Category 1), updated May 2026.
  6. Enclomiphene ZA-301 phase 3 trial record and posted results (NCT01532414). ClinicalTrials.gov.
  7. Pregnyl (chorionic gonadotropin for injection) prescribing information. DailyMed.
  8. Ovidrel (choriogonadotropin alfa) prescribing information, section 12.3. DailyMed.
  9. Ghobadi C, et al. Single-dose pharmacokinetic study of clomiphene citrate isomers. 2009.
  10. Enclomiphene ZA-302 phase 3 trial record and posted results (NCT01739595). ClinicalTrials.gov.
  11. Wiehle RD, et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II trial vs topical testosterone. BJU Int. 2013.

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