Enclomiphene vs. TRT: How to Choose

TRT adds testosterone from outside the body, by injection, pellet, or gel. Your levels go up because you're supplying the hormone directly.

Enclomiphene works upstream. It blocks estrogen's “slow down” signal to the brain, so the pituitary sends more of two signaling hormones, LH and FSH, to the testes. The testes respond by making more of your own testosterone. Because the signal to the testes stays on, sperm production generally continues. With TRT, that signal shuts off, which is why TRT lowers sperm counts.

Enclomiphene has been studied in a handful of trials, most of them sponsored by the company that developed it. In those trials, lasting 16 weeks to six months, enclomiphene raised testosterone into the normal range about as well as a testosterone gel did. The difference was what happened to LH, FSH and sperm: on enclomiphene they stayed up, and on gel they fell.

What the trials didn't show matters just as much. They measured hormone levels and sperm concentration, not how men felt. When the FDA reviewed enclomiphene, it concluded the studies hadn't demonstrated a clinically meaningful improvement in the symptoms of low testosterone. So the fair summary is this: enclomiphene can raise your own testosterone while preserving sperm production, and whether that translates into feeling better hasn't been well studied. Everyone responds differently.

Enclomiphene is not an FDA-approved medication. The company that developed it applied for approval, and the FDA declined to approve it in 2015. Today it's available as a compounded medication, prepared by a licensed compounding pharmacy for a patient whose provider prescribes it. In 2022, an FDA advisory committee voted against adding enclomiphene to the list of substances pharmacies may compound, and the FDA has not made a final decision. While that evaluation continues, enclomiphene remains available as a compounded medication. It is not FDA-approved, and no one should describe it that way.

Clomiphene citrate, the active ingredient in Clomid®, is a related, FDA-approved medication for infertility in women. Chemically, clomiphene is a mix of two mirror-image forms, and enclomiphene is one of them. That doesn't make enclomiphene an approved drug. Clomiphene is sometimes used off-label in men. Enclomiphene is not the same medication; it's a separate compounded product.

Your provider may bring it up if:

• Your low testosterone comes from a weak signal from the brain (what clinicians call secondary hypogonadism), rather than from testes that can't respond.
• You want to have children now or later. The American Urological Association says clinicians may use medications in this family for men with testosterone deficiency who want to maintain fertility.
• You'd rather take a tablet than give yourself injections or have pellets placed.

It is not a fit when the testes themselves have stopped responding. If LH and FSH are already high, there's no signal left to boost. That's why the first-visit labs include those hormones.

TRT has been used for decades and is the standard treatment when the testes can't make enough testosterone. It comes as injections (usually weekly or split into two smaller weekly doses), pellets placed under the skin every few months, and gels. A few facts your provider will walk through:

• TRT suppresses sperm production. For many men it recovers after stopping, but recovery can take up to two years, and it isn't guaranteed. The AUA advises against starting TRT if you're currently trying to conceive.
• TRT needs monitoring. Red blood cell count (hematocrit) is checked before starting and on a schedule, because TRT can raise it. PSA is checked in men over 40. Estradiol is checked when symptoms call for it.
• Most TRT pellets are compounded. One FDA-approved testosterone pellet product exists for men; other pellets are prepared by compounding pharmacies and are not FDA-approved.

Reported side effects include headache, hot flushes, nausea, mood changes, and higher estradiol. Visual changes are rare but should be reported right away, because with related medications they have sometimes been lasting. There's no official monitoring guideline for enclomiphene, so careful providers borrow from the TRT framework: testosterone, LH and FSH, estradiol, hematocrit, and PSA based on age, rechecked after starting and then on a schedule.

Are my LH and FSH low or high? Do I want children in the next few years? Would I keep up with weekly injections? What will we recheck, and when? What happens if it isn't working?