HCG Shortage 2026: What Men on TRT Need to Know About Fertility Preservation Alternatives

What is the HCG shortage and what should men on TRT do?

The HCG shortage 2026 is a layered supply problem that has made human chorionic gonadotropin difficult or impossible to fill at most U.S. pharmacies. The root causes are regulatory (the BPCIA reclassification of HCG as a biologic, which closed off the 503A and 503B compounding pathways most TRT prescribers had used) and manufacturing (intermittent supply gaps for the two FDA-approved branded products, Pregnyl and Novarel). Men on TRT who relied on HCG to preserve fertility or testicular function have practical alternatives — recombinant LH, hMG (Menopur), and oral SERMs like clomiphene and enclomiphene — but each works differently, costs differently, and fits a different clinical situation.

If you are on TRT and your prescriber discontinued HCG because the pharmacy could not fill it, this is a common experience in 2025 and 2026. The right next step is a structured conversation with the prescriber — ideally with a urologist or reproductive endocrinologist looped in if conception is on the table — to choose the alternative that matches your goal. For background on what HCG itself does on TRT, the foundational article is HCG on TRT: how it preserves fertility and testicular function; this article picks up where that one ends, focused on the 2026 supply landscape and the alternatives.

Why is HCG suddenly hard to get?

HCG was widely available in U.S. pharmacies for decades — both as the FDA-approved branded products (Pregnyl from Organon, Novarel from Ferring, and the now-discontinued Profasi) and as compounded HCG from 503A and 503B compounding pharmacies. The compounded supply was the workhorse of the men's hormone market: low cost, flexible dosing, and easy to reconstitute at the dose ranges used alongside TRT (typically 250-500 IU two or three times per week, drawn from the Coviello dose-finding work).

Two regulatory pressures collapsed that landscape over the past several years. First, the Biologics Price Competition and Innovation Act of 2009 (BPCIA, Section 351(i) of the Public Health Service Act) defined HCG as a biological product and gave manufacturers a transition window. The deadline at the end of March 2020 reclassified HCG as a biologic for FDA purposes, which restricted the compounding routes available because compounding pharmacies generally cannot compound from biologics in the same way they compound from small molecules. Second, the FDA stepped up enforcement of 503A and 503B compounding rules during 2023-2025 — including warning letters and section 503A bulks list reviews — which further narrowed which compounding pharmacies were willing to dispense HCG.

Layer on top of that the manufacturing reality. Pregnyl and Novarel have both appeared on the FDA drug shortage database during 2024-2026 for various combinations of manufacturing delays, packaging issues, and shifting demand from the IVF market. The result for a man on TRT is a shelf that used to be reliably stocked and is now empty, with the patient holding a prescription and no straightforward way to fill it.

HCG availability timeline (2019-2026)

The chart below illustrates the cascade. It is a simplified visual of the regulatory and manufacturing pressures, not a complete supply chain map.

The BPCIA biologic reclassification deadline

The single most important regulatory event behind the shortage is the BPCIA transition deadline. The Biologics Price Competition and Innovation Act, passed as part of the Affordable Care Act in 2010, established the regulatory pathway for biosimilars in the United States — the rough analog of the small-molecule generic pathway, but for biological products. Section 351(i)(1) of the Public Health Service Act defines biological products to include hormones and other glycoproteins that meet specific structural criteria.

HCG is a glycoprotein hormone, and the FDA reclassified it as a biological product under the BPCIA framework. Manufacturers and pharmacies had a transition window that closed on March 23, 2020, after which any HCG product had to be either an FDA-approved branded biologic, an FDA-approved biosimilar, or compounded under restrictions that apply to biologics.

Why this matters in practical terms:

• 503A pharmacies (which compound for individual prescriptions) face significant restrictions when the starting material is a biologic. Many simply stopped compounding HCG to avoid regulatory risk.
• 503B outsourcing facilities (which produce sterile compounds for office use) face similar but not identical limits. The FDA 503A bulks list — which catalogs which substances may be compounded under 503A — has been the focus of multiple FDA reviews where HCG's status has been debated.
• The pathway forward for affordable supply is essentially a biosimilar — but biosimilar approval takes years and is driven by manufacturer economics. As of May 2026, no U.S. HCG biosimilar has reached the market.

The BPCIA was not designed to disrupt male hormone therapy — it was designed to enable competition in the broader biologics market. The disruption to HCG supply is a downstream side effect of an unrelated regulatory architecture.

503A vs 503B compounding pharmacies and what changed

Most men on TRT who used HCG before 2024 received it from a compounding pharmacy, not from a branded retail prescription. Two regulatory categories matter here, and the difference shapes which alternatives are still accessible.

503A pharmacies

503A pharmacies compound prescriptions on a patient-specific basis. These are the traditional compounding pharmacies men encounter through telehealth TRT clinics. Under FDA enforcement, 503A facilities can compound substances on the FDA bulks list or substances that are components of FDA-approved drugs. After the BPCIA deadline, HCG's status as a biologic narrowed the pathway; many 503A pharmacies now decline HCG prescriptions citing regulatory uncertainty.

503B outsourcing facilities

503B outsourcing facilities operate under tighter manufacturing standards and can supply prescribers' offices in bulk. They are subject to current good manufacturing practice (cGMP) inspection and have a different bulks list framework. Some 503B facilities continued to supply HCG longer than 503A pharmacies did, but FDA enforcement actions and inspection findings during 2024-2025 reduced that channel as well. The FDA 503B bulks list and ongoing rule reviews are the public record of what is currently allowed.

What this means for a TRT patient

A patient who used to fill HCG at a 503A pharmacy through a telehealth TRT clinic in 2022 is the patient most likely to be told in 2026 that the pharmacy no longer fills HCG. The branded products (Pregnyl, Novarel) still exist, but at retail prices that can be ten times what compounded HCG cost — and even those are intermittently on the FDA shortage list.

FDA drug shortage list status for HCG products

The FDA Drug Shortage Database (CDER) tracks current and resolved shortages reported by manufacturers. Both Pregnyl and Novarel have appeared on that database at points during 2024-2026 with reasons typically listed as "manufacturing delay," "increased demand," or "shipping/packaging issue." Resolution dates have been pushed back multiple times.

For up-to-date status on any specific product, the FDA shortage database (accessfdadrugs.com or accessdata.fda.gov/scripts/drugshortages) is the authoritative source. Status changes weekly.

Pro tip: when calling a pharmacy about HCG fill status, ask specifically whether the issue is upstream (the manufacturer cannot ship) or local (this pharmacy is not currently dispensing). Branded HCG that is on the FDA shortage list cannot be filled regardless of pharmacy. Branded HCG that is in stock somewhere else may still be fillable through a different pharmacy network or specialty pharmacy.

What can replace HCG on TRT? Alternatives at a glance

No alternative is a true pharmacological substitute for HCG — each works differently. The relevant choices are:

1. Recombinant LH (lutropin alfa, brand Luveris). A direct LH replacement that binds the LH receptor on Leydig cells, much like HCG does. Closest mechanistic substitute; high cost.
2. Human menopausal gonadotropin (hMG, brand Menopur). A urinary-derived preparation containing both LH and FSH activity. Used in fertility induction protocols; often paired with HCG when HCG is available.
3. Clomiphene citrate (Clomid) or enclomiphene. Oral SERMs that block estrogen feedback at the hypothalamus, raising endogenous LH and FSH. Mechanism is upstream of HCG — generally used as monotherapy in place of TRT, not alongside it.
4. HCG biosimilars in the development pipeline. Several international manufacturers have HCG candidates in various stages; none yet on the U.S. market as of May 2026.
5. Sperm cryopreservation as a fallback. Not a pharmacological alternative, but the highest-confidence fertility insurance and the option some prescribers raise first for men with near-term conception plans.

Alternative comparison matrix

Recombinant LH (lutropin alfa)

Recombinant LH — sold internationally as Luveris (lutropin alfa, EMD Serono) — is a recombinant version of human luteinizing hormone produced in Chinese hamster ovary cells. It binds the same LH receptor on testicular Leydig cells that HCG binds, which makes it the closest mechanistic substitute for HCG of any pharmacological alternative.

Practical limitations:

• Luveris is FDA-approved for use in women with hypogonadotropic hypogonadism undergoing controlled ovarian stimulation, not for male hypogonadism. Use in men is off-label.
• U.S. availability has been intermittent. Luveris was withdrawn from the U.S. market for periods during 2010-2020 and remains less commonly stocked than its European counterpart.
• Half-life is shorter than HCG (roughly 10-12 hours versus 24-36 hours for HCG), which means more frequent injections at equivalent biological effect.
• Cost is substantially higher than compounded HCG — typical pricing for Luveris equivalents in fertility induction protocols is $1,000-$3,000 per month at clinical doses.

For the man on TRT who relied on HCG for testicular volume and basic spermatogenesis maintenance, recombinant LH is mechanistically appropriate but not always practically accessible. It is most likely to come up in cases where a urologist or reproductive endocrinologist is involved and where insurance covers fertility induction.

Human menopausal gonadotropin (hMG / Menopur)

Human menopausal gonadotropin (hMG), sold as Menopur (Ferring), is a urinary-derived preparation that contains both LH and FSH activity. Each 75 IU vial of Menopur typically contains 75 IU of FSH and 75 IU of LH activity (with the LH activity supplied largely by HCG present in the menopausal urine source — a regulatory irony given the HCG shortage context).

hMG is FDA-approved for ovulation induction in women, and use in men with hypogonadotropic hypogonadism for fertility induction is well-established off-label and is supported by decades of literature. The most-cited male protocols for hypogonadotropic hypogonadism (HH) use hMG combined with HCG to drive complete spermatogenesis — for example, work by Bhasin, Liu, Matsumoto, Sussman, and others.

Where hMG fits in the post-HCG-shortage landscape:

• As an HCG substitute when HCG cannot be obtained. Because Menopur contains both LH and FSH activity, a man on TRT can in principle receive Menopur to provide gonadotropin signal for testicular function — though there is much less published experience with Menopur monotherapy in this exact scenario than with HCG.
• As an addition when HCG alone is not producing adequate spermatogenesis. This is the classic indication — adding FSH activity for HH patients who have responded to HCG but remain below target sperm parameters.
• For men actively trying to conceive. Menopur is the more commonly stocked product at fertility clinics and reproductive endocrinology offices, which sometimes have access when retail pharmacies do not.

Cost: typical Menopur monthly cost at fertility-induction doses runs $1,500-$3,000 without insurance, with significant variance across pharmacies and indications.

Clomiphene and enclomiphene as fertility-preservation tools

Clomiphene citrate and enclomiphene operate at a different point on the HPG axis than HCG. Both are oral selective estrogen receptor modulators (SERMs) that block estrogen feedback at the hypothalamus, increasing GnRH and downstream LH and FSH output. The result is increased endogenous testosterone production and supported spermatogenesis — without the suppressive pharmacology of exogenous testosterone.

For a man on full-dose TRT, this mechanism is incompatible: TRT suppresses the hypothalamus, so a SERM cannot meaningfully raise LH and FSH above the suppressed baseline. SERMs are therefore not generally added on top of TRT. Instead, the typical use case during the HCG shortage is a man who is willing to switch from TRT to SERM monotherapy because preserving fertility is now his primary goal.

Clomiphene citrate

Clomiphene is a mixture of two isomers (zuclomiphene and enclomiphene). The trans-isomer (enclomiphene) is responsible for most of the LH/FSH-raising effect; the cis-isomer (zuclomiphene) has more estrogenic activity and a longer half-life. Clomiphene has been used off-label in men for decades. The Katz/Kim 2012 series, the Ramasamy 2014 work, and the Habous 2018 trial are commonly cited.

Enclomiphene

Enclomiphene isolates the trans-isomer. Industry-funded Phase III trials of enclomiphene citrate (Wiehle 2014, Kaminetsky 2013) reported significant LH, FSH, and total testosterone increases in men with secondary hypogonadism without the estrogenic side-effect profile of mixed clomiphene. Sperm parameters were generally preserved or improved relative to TRT. Enclomiphene was the subject of an FDA Complete Response Letter and has had a complicated U.S. approval path; in 2026 it is most commonly accessed through compounding pharmacies for off-label use.

For a deeper comparison see Clomid vs TRT and enclomiphene vs TRT.

HCG biosimilars and what is in the pipeline

The BPCIA created the regulatory pathway for biosimilar versions of HCG. As of May 2026, no HCG biosimilar is approved and marketed in the United States.

What this looks like in practice:

• The FDA Purple Book lists licensed biological products and any approved biosimilars. HCG (chorionic gonadotropin) appears with the branded reference products (Pregnyl, Novarel) but no listed biosimilars at the time of this article.
• International biosimilar candidates exist — several Indian and Chinese manufacturers produce HCG that is sold in their domestic markets, but FDA approval requires specific U.S. clinical and analytical packages that none has yet completed publicly.
• The economics of HCG biosimilar development are not as favorable as for higher-revenue biologics like adalimumab (Humira) or rituximab (Rituxan). Manufacturers face the question of whether the male hormone market plus the IVF market plus residual fertility induction demand is large enough to justify the biosimilar approval pathway investment.

Watch the FDA Purple Book and the FDA biosimilar pipeline announcements for changes. The first U.S.-approved HCG biosimilar — whenever it arrives — will likely shift the supply landscape significantly.

Clinical evidence for each alternative

The HCG-on-TRT evidence base — built on the Coviello 2005 dose-finding study and the Hsieh 2013 observational cohort — is far more developed than the evidence base for any alternative used specifically for the post-shortage scenario of fertility preservation in a man already on TRT. The published literature on alternatives is mostly built around two different clinical contexts: hypogonadotropic hypogonadism fertility induction and SERM monotherapy for secondary hypogonadism.

Recombinant LH evidence

Bouloux et al. (Fertility and Sterility 2002) and Burgues et al. evaluated recombinant LH in men with hypogonadotropic hypogonadism. The studies showed that lutropin alfa, when added to FSH or used as an LH replacement, supported testicular volume increase and sperm production in men with HH. The protocols used, however, were not the chronic low-dose maintenance pattern that HCG supplies on TRT — they were higher-frequency fertility induction protocols. Direct head-to-head data comparing recombinant LH to HCG specifically for the TRT-adjunct use case is limited.

hMG evidence

Multiple decades of literature support hMG (with or without HCG) for fertility induction in men with HH. Liu et al. and Buchter et al. reported high rates of spermatogenesis and clinical pregnancies in HH patients on hMG-based protocols. Wenker et al. (Journal of Sexual Medicine 2015) reported on combination therapy for spermatogenesis recovery after testosterone use, providing data on how HCG-based regimens (often with adjunct FSH or hMG) restore spermatogenesis after exogenous testosterone exposure. The Wenker study cohort included men recovering from various androgen exposures, with general recovery to non-azoospermic status in most participants over multi-month follow-up.

Clomiphene and enclomiphene evidence

Habous et al. (BJU International 2018) directly compared clomiphene citrate to testosterone replacement in men with hypogonadism, reporting comparable testosterone increases at lower cost and with preserved spermatogenesis on clomiphene. Ramasamy et al. (Asian Journal of Andrology 2014) and Katz et al. (BJU 2012) provide the broader off-label evidence base. For enclomiphene, Wiehle et al. (Fertility and Sterility 2014) reported the Phase III data in secondary hypogonadism; sperm concentrations were maintained on enclomiphene and reduced on testosterone gel.

Sperm parameter outcomes by alternative (illustrative)

A practical decision framework

Deciding among the alternatives is a prescriber-led process, but the framework most commonly discussed in male reproductive medicine reviews boils down to three questions: (1) what is the fertility timeline, (2) what is on the formulary or available, and (3) what is the patient willing to do regarding TRT itself.

Decision flowchart

Monitoring and labs that change with the alternative

Switching from HCG to an alternative changes the monitoring picture. The relevant labs depend on the alternative chosen.

Labs that change with the choice

• If switching to recombinant LH or hMG: total testosterone, sensitive estradiol (LC-MS/MS), SHBG, and sperm parameters at intervals. Monitoring frequency is similar to HCG monitoring; sensitive estradiol may rise as testicular testosterone production resumes and aromatizes.
• If switching to clomiphene or enclomiphene monotherapy (off TRT): total and free testosterone, LH, FSH, sensitive estradiol, sperm parameters at 3 and 6 months. The whole HPG axis is now active, so LH and FSH become meaningful again — they are not on TRT, where they read suppressed.
• If pausing TRT for fertility induction: add prolactin (to rule out a pituitary cause that may have been missed) and consider an FSH measurement to confirm responsiveness before the protocol is locked in.
• Hematocrit, PSA, and lipids: these continue on the standard TRT cadence regardless of alternative, per Endocrine Society and AUA guidance. The 2018 Endocrine Society clinical practice guideline (Bhasin et al., JCEM) is the underlying source for monitoring intervals.

See our TRT blood work schedule for the standard monitoring cadence and estradiol on TRT for E2-specific guidance during a protocol change.

What not to do during the shortage

Three patterns appear regularly in patient forums and TRT communities and deserve a direct flag:

1. Do not buy HCG from research-chemical websites or unregulated overseas sources. HCG sold without a prescription is frequently counterfeit, contaminated, mis-dosed, or simply something else. The legal risk and the contamination risk are both real. The DEA and FDA have flagged repeated cases of misbranded peptides and gonadotropins in the 2024-2025 enforcement record.
2. Do not stop TRT abruptly without a prescriber-led plan. Discontinuing testosterone without a transition strategy can produce months of HPG axis suppression, low energy, and mood disruption. Coming off TRT is a deliberate process; for context see coming off TRT and HPTA recovery.
3. Do not assume a research-grade compound is the same as a pharmaceutical-grade biologic. Even branded HCG and recombinant LH have batch-to-batch variability handled by cGMP processes. A research-chemical product has none of those quality controls. The risk profile is fundamentally different.

The bottom line

The HCG shortage 2026 is a real, persistent supply problem with regulatory roots in the BPCIA biologic reclassification and manufacturing roots in intermittent Pregnyl and Novarel availability. Men on TRT who used HCG for fertility preservation or testicular function maintenance have practical alternatives — recombinant LH, hMG (Menopur), oral SERMs (clomiphene, enclomiphene), and sperm cryopreservation — but each of these tools matches a different clinical situation, has a different cost profile, and comes with different evidence support.

The right answer for any individual depends on conception timeline, willingness to pause or modify TRT, insurance coverage, and prescriber expertise. There is no universal substitute. The path forward is a structured conversation with the prescriber managing TRT, ideally with a urologist or reproductive endocrinologist involved if conception is on the table within the next several years.

Watch the FDA drug shortage database and the FDA Purple Book for status changes. The first U.S.-approved HCG biosimilar will reshape this landscape. Until then, the alternatives above are the working tool kit.