Hydroxyprogesterone

Pronunciation: pronunciation varies by local usage.

Generic name: hydroxyprogesterone caproate
Brand names: Makena (US — preterm-birth indication, withdrawn), Proluton Depot (EU — suspended), Progesterone Retard Pharlon (EU — suspended), Lentogest (EU — suspended)
Drug class: Progestin (synthetic progesterone derivative)
Form: Oily solution for intramuscular injection; strength and exact formulation are product- and indication-specific
Route: Intramuscular injection (given by a healthcare professional)
Legal status: Prescription-only injectable where any form remains marketed. Its best-known use — preterm-birth prevention — is no longer an approved/authorised use in the US or EU (see Regulatory status).

Supply Rules Vary

Trade names by country: United States

What hydroxyprogesterone caproate is and how it works

Hydroxyprogesterone caproate is a synthetic, long-acting injectable form of progesterone with two separate, distinct regulatory histories that must not be confused with each other. Its best-known modern use — reducing the risk of recurrent preterm birth (sold in the US as Makena and as generic equivalents) — is NOT currently an approved or legally marketable use in the United States: the FDA ordered withdrawal of Makena's approval, and every generic equivalent approved for the same indication, effective April 6, 2023, after the required confirmatory trial (PROLONG) failed to show it reduced preterm birth risk or improved newborn outcomes. In the European Union, the only nationally authorised hydroxyprogesterone caproate products (Proluton Depot, Progesterone Retard Pharlon, and Lentogest — authorised only in Austria, France, and Italy) had their marketing authorisations suspended EU-wide from 26 June 2024, for the same lack-of-efficacy finding plus a possible, unconfirmed increased cancer risk identified in offspring exposed to the drug before birth. Separately, and unaffected by any of this, an older, differently indicated hydroxyprogesterone caproate injection remains actively approved and marketed in the United States for palliative treatment of advanced adenocarcinoma of the uterine corpus, for managing amenorrhea and abnormal uterine bleeding caused by hormonal imbalance, and as a diagnostic test for endogenous estrogen production — none of which involve pregnancy or preterm-birth prevention. (1) (2) (4) (5)

If you, or someone you know, is currently receiving Makena, a compounded 17-OHPC product, or any hydroxyprogesterone caproate injection for pregnancy/preterm-birth reasons, this is not a currently approved treatment in the US or EU and you should speak with your obstetric care team as soon as possible about what this means for your care. If you are receiving a hydroxyprogesterone caproate injection for a gynecologic or oncology indication in the US, that remains a separately approved, currently marketed use — this page keeps the two apart deliberately.

What hydroxyprogesterone caproate is used for

Preterm-birth prevention — WITHDRAWN in the US (2023) and SUSPENDED in the EU (2024)

This was hydroxyprogesterone caproate's best-known modern use (as Makena and generic equivalents in the US; as Proluton Depot and related brands in parts of the EU), given weekly by injection from about 16 to 37 weeks of pregnancy to women with a history of a prior spontaneous preterm singleton birth. It is no longer an approved or legally marketable use in the United States (FDA-ordered withdrawal, effective April 6, 2023) or in the European Union (EU-wide suspension, effective 26 June 2024). Do not start or continue this specific use without discussing current alternatives with your obstetric care team. (1) (2) (5) (6)

Palliative treatment of advanced adenocarcinoma of the uterine corpus (US only, currently marketed)

In the United States, a separate, currently active hydroxyprogesterone caproate injection is approved for palliative (symptom- and disease-directed, not curative) treatment of Stage III or IV adenocarcinoma of the uterine corpus (womb lining cancer), as part of a specialist oncology treatment plan. (4)

Amenorrhea and abnormal uterine bleeding due to hormonal imbalance (US only, currently marketed)

Also approved in the United States for managing amenorrhea (absent periods) and abnormal uterine bleeding caused by a hormonal imbalance, once other organic (structural/pathological) causes have been ruled out by a clinician. (4)

Test for endogenous estrogen production (US only, currently marketed)

A single-dose hydroxyprogesterone caproate injection can be used by a clinician as a diagnostic test of the body's own estrogen production. This is a diagnostic use only and is not a pregnancy test. (4)

Before taking hydroxyprogesterone caproate

Do not take / not appropriate for

Do not receive hydroxyprogesterone caproate if you have known or suspected breast cancer or another hormone-sensitive cancer, undiagnosed abnormal vaginal bleeding, liver dysfunction or liver tumors, a missed abortion, a current or past thrombotic/thromboembolic disorder (blood clot, stroke, heart attack), or a known hypersensitivity to the drug or its ingredients. (all currently marketed products) (4) (3)

Tell your clinician about

Any personal or family history of blood clots, stroke, heart attack, or other thrombotic/thromboembolic problems.
Any history of breast cancer or other hormone-sensitive cancer.
Liver disease, liver tumors, or jaundice.
Diabetes or impaired glucose tolerance.
Any unexplained vaginal bleeding that has not yet been evaluated.
Pregnancy, plans for pregnancy, or breastfeeding — the currently marketed US indications are not pregnancy-related, and this is not a currently approved pregnancy treatment.
All other medicines, herbal products, and supplements you take.

(4) (3)

How to take hydroxyprogesterone caproate

Hydroxyprogesterone caproate is given only as an intramuscular injection by a doctor or nurse — it is never self-administered, swallowed, or taken at home without direct clinical supervision.
The dose, injection frequency, and treatment duration depend entirely on the specific approved indication (oncology, amenorrhea/abnormal uterine bleeding, or diagnostic estrogen-production testing) and vary by country and product. There is no single universal dose.
Do not seek this injection for preterm-birth prevention outside of a documented, currently approved regulatory pathway in your country; discuss any pregnancy-related progesterone support options with your obstetric team.

(4)

Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6)

Missed dose

Because this is a clinician-administered injection on a schedule set by your treatment team, contact your clinic directly to reschedule a missed appointment. Do not attempt to self-correct a missed dose.

Overdose

Specific overdose data are not detailed in the reviewed prescribing information. Because this medicine is given only under direct medical supervision, an accidental overdose is managed by the treating clinical team. If you have any concern about an incorrect dose having been given, contact the treating clinic or emergency services.

Side effects

Side effects differ by indication and dose (the oncology dose is far higher than the historic pregnancy-support dose). The list below reflects the currently marketed US oncology/gynecologic product's label.

Injection-site reactions

What to notice: Pain, swelling, redness, itching, or a firm lump where the injection was given.

What to do: Tell your clinical team if a reaction is severe, spreading, or not improving. (4)

Fluid retention

What to notice: Swelling of the hands, ankles, or feet, or unexpected weight gain.

What to do: Report to your clinical team, especially if you have heart, kidney, or liver problems. (4)

Mood changes

What to notice: New or worsening low mood or depression.

What to do: Discuss with your clinical team; do not stop treatment on your own. (4)

Reduced glucose tolerance

What to notice: Higher-than-usual blood sugar readings, increased thirst, or increased urination, particularly if you have diabetes.

What to do: Monitor blood sugar as advised and tell your clinical team of any change. (4)

Serious warnings

Thromboembolic disease (blood clots, stroke, heart attack, pulmonary embolism) — emergency

Symptoms: Sudden leg pain/swelling, chest pain, breathlessness, sudden severe headache, slurred speech, or one-sided weakness.

Action: Call emergency services or go to the emergency department immediately. The clinical team will assess and decide on any treatment change. (4)

Severe allergic reaction (anaphylaxis) — emergency

Symptoms: Hives, facial or throat swelling, difficulty breathing or swallowing.

Action: Seek emergency medical care immediately. (4)

Sudden vision changes — urgent

Symptoms: New blurred vision, loss of vision, double vision, or bulging eyes.

Action: Seek urgent medical assessment; report to your clinical team without delay. (4)

Being offered or continued on hydroxyprogesterone caproate / Makena specifically for preterm-birth prevention — urgent

Symptoms: Not a symptom-based warning — a regulatory-status warning: this specific use is no longer FDA-approved (US, since April 2023) or authorised (EU, since June 2024).

Action: Raise this directly with your obstetric care team so they can explain the current evidence and discuss any alternative options with you. (1) (5)

Interactions

Medicine or test	Effect	Action
No specific drug-drug interaction data identified in the reviewed sources	The reviewed prescribing information for the currently marketed US product describes major class-level risks (thromboembolic disease, hepatic and glucose effects) rather than a specific drug-interaction table.	Always tell every clinician and pharmacist involved in your care about all medicines, herbal products, and supplements you take, so they can assess your individual risk.

Pregnancy, breastfeeding, kidney/liver function, age

Pregnancy

None of the currently active, approved indications for hydroxyprogesterone caproate (advanced uterine adenocarcinoma, amenorrhea/abnormal uterine bleeding, estrogen-production testing) are pregnancy-related, and a missed abortion is a specific contraindication. The historic pregnancy-related use (preterm-birth prevention) is the specific use that has been withdrawn in the US and suspended in the EU — do not assume this is still an available pregnancy treatment. (4) (1)

Patients with liver disease

Contraindicated in liver dysfunction or liver tumors. Report any signs of jaundice, dark urine, or severe abdominal pain immediately. (4)

Patients with diabetes or impaired glucose tolerance

Hydroxyprogesterone caproate can reduce glucose tolerance; blood sugar monitoring may need to be more frequent. (4)

Patients with a history of thromboembolic disease

Contraindicated in patients with current or past blood clots, stroke, or heart attack, given the drug's own thromboembolic risk. (4)

Elderly patients

Specific elderly-population dosing or safety data were not identified in the reviewed sources for the currently marketed product. This gap is disclosed honestly rather than assumed.

Breastfeeding

The US label for hydroxyprogesterone caproate injection states, under nursing mothers, that detectable amounts of progestins have been identified in the milk of mothers receiving the drug, and that many studies have found no adverse effects of progestins on breastfeeding performance or on the health, growth or development of the infant. There is no dedicated LactMed record for hydroxyprogesterone caproate, so there is no larger body of published human breastfeeding data specific to this drug beyond that label statement. Whether to use it while breastfeeding is a decision for the prescriber, taking account of the reason it is being given. (4)

Monitoring

Before starting

Confirm the specific approved indication being treated (oncology, amenorrhea/abnormal uterine bleeding, or diagnostic estrogen testing) — never assume preterm-birth prevention, which is not a currently approved use in the US or EU.
Review personal and family history of thromboembolic disease, breast or hormone-sensitive cancer, and liver disease.
Baseline liver function and, in patients with diabetes, baseline blood glucose.

During treatment

Watch for and immediately report any signs of blood clots, sudden vision changes, jaundice, or severe allergic reaction.
Periodic reassessment of the treatment indication and ongoing need, particularly given the 2023/2024 regulatory findings that affected the same drug substance's pregnancy-related use.
Blood glucose monitoring in patients with diabetes or risk factors.

(4)

Storage

Specific storage instructions are not provided in the reviewed notes; this medicine is stored and handled by the treating clinic or pharmacy, not by patients at home. Refer to the current local prescribing information for exact storage conditions.

Professional information

Clinician-facing summary. Always consult current local prescribing information and, for the withdrawn/suspended preterm-birth indication, the relevant regulator's own withdrawal/suspension notice, as this area has changed materially since 2023.

United States — currently marketed oncology/gynecologic product

Indication: Advanced (Stage III/IV) adenocarcinoma of the uterine corpus (palliative); amenorrhea/abnormal uterine bleeding due to hormonal imbalance without organic pathology; endogenous estrogen-production testing

Dose summary: Amenorrhea/abnormal bleeding: 375 mg cyclically every 4 weeks. Advanced adenocarcinoma: 1,000 mg or more, one or more times weekly. Estrogen-production test: 250 mg single dose. Exact regimen is prescriber-determined.

Renal context: Not specifically detailed in the reviewed label beyond general hepatic/thromboembolic contraindications. (4)

United States — historic preterm-birth-prevention regimen (WITHDRAWN, not current guidance)

Indication: Reduce risk of recurrent preterm birth in singleton pregnancy with a history of prior singleton spontaneous preterm birth

Dose summary: Historic regimen (no longer an approved use as of April 6, 2023): 250 mg (1 mL) intramuscularly once weekly, starting 16 weeks 0 days–20 weeks 6 days of gestation through week 36 6/7 or delivery. Shown here only for informational/historical accuracy, not as current treatment guidance.

Renal context: Not applicable — historic indication, withdrawn. (3) (1)

European Union (Austria, France, Italy — only countries where ever authorised)

Indication: Preterm-birth prevention and related uses under Proluton Depot / Progesterone Retard Pharlon / Lentogest

Dose summary: Marketing authorisations for all indications of these products were suspended EU-wide effective the CMDh's 26 June 2024 endorsement of PRAC's recommendation. No current authorised dosing exists.

Renal context: Not applicable — suspended. (5) (6)

United Kingdom, Australia, New Zealand, Canada

Indication: Unverified

Dose summary: No current, live-verifiable marketing authorisation, product information, or dosing guidance was located for any of these countries within this session's research. Regulatory status is not asserted either way.

Renal context: Not applicable — unverified.

Frequently asked questions

Was Makena (hydroxyprogesterone caproate) withdrawn from the market?

Yes, for its preterm-birth-prevention use. The FDA ordered withdrawal of approval for Makena and every generic equivalent approved for that same indication, effective April 6, 2023, after the required confirmatory trial failed to show a real reduction in preterm birth or an improvement in newborn outcomes. (1) (2)

Why was it withdrawn?

The FDA required a confirmatory trial (known as PROLONG) after granting accelerated approval in 2011. That trial did not show that Makena reduced the risk of preterm birth or improved outcomes for babies, in the overall population or in any studied subgroup. With no shown benefit, the FDA concluded no level of risk was justified. (1)

Is hydroxyprogesterone caproate still used for anything in the United States?

Yes — a separate, older, currently active approval covers palliative treatment of advanced (Stage III/IV) adenocarcinoma of the uterine corpus, management of amenorrhea and abnormal uterine bleeding caused by hormonal imbalance, and testing for endogenous estrogen production. None of these involve pregnancy or preterm-birth prevention, and this approval was not affected by the 2023 withdrawal. (4)

What happened in the European Union?

The only EU-authorised hydroxyprogesterone caproate products (Proluton Depot, Progesterone Retard Pharlon, and Lentogest — authorised only in Austria, France, and Italy) had their marketing authorisations suspended across the EU, effective the CMDh's 26 June 2024 endorsement of a PRAC recommendation. The review cited both a lack of shown efficacy for preventing preterm birth and a possible, unconfirmed increased cancer risk identified in offspring exposed to the drug before birth. (5) (6)

Is hydroxyprogesterone caproate still available in the UK, Australia, New Zealand, or Canada?

This could not be confirmed from a live official regulator source (UK electronic Medicines Compendium, Australian TGA/ARTG, New Zealand Medsafe, or Health Canada's Drug Product Database) at the time of writing. Its status in these countries is not asserted either way — ask your local pharmacist or prescriber for the current position where you are.

I am currently receiving Makena, a compounded 17-OHPC product, or a similar injection during pregnancy — what should I do?

Speak with your obstetric care team as soon as possible. This specific use is no longer an FDA-approved or EU-authorised treatment, and your clinical team can explain the current evidence and discuss what it means for your care and any alternatives. (1)

Does the cancer-risk signal mentioned by EU regulators mean hydroxyprogesterone caproate causes cancer?

The EU review identified a statistically significant, roughly two-fold increase in cancer risk among people exposed to the drug before birth, but described this as "possible but unconfirmed," and the absolute incidence remained low (under 25 per 100,000 person-years). This was one of two reasons cited for suspension, alongside a lack of shown benefit; it is not established as a confirmed causal link. (5)

What is the generic name of Hydroxyprogesterone?

The generic name is hydroxyprogesterone caproate. It is sold under brand names including Makena (US — preterm-birth indication, withdrawn), Proluton Depot (EU — suspended), Progesterone Retard Pharlon (EU — suspended), Lentogest (EU — suspended). (1) (4) (5)

What class of drug is hydroxyprogesterone caproate?

Hydroxyprogesterone is classed as: Progestin (synthetic progesterone derivative). (1) (4) (5)

References

Makena (hydroxyprogesterone caproate injection) InformationU.S. Food and Drug Administration · United States · accessed 2026-07-31 · source 1
Final Decision on Withdrawal of MAKENA (Hydroxyprogesterone Caproate) and Eight Abbreviated New Drug Applications Following Public HearingU.S. Food and Drug Administration / Federal Register · United States · accessed 2026-07-31 · source 2
Hydroxyprogesterone Caproate Injection (generic, preterm-birth-prevention labeling)U.S. National Library of Medicine, DailyMed · United States · accessed 2026-07-31 · source 3
Hydroxyprogesterone Caproate Injection, USP (separate ANDA, oncology/gynecologic indications)U.S. National Library of Medicine, DailyMed · United States · accessed 2026-07-31 · source 4
Hydroxyprogesterone caproate-containing medicinal products — Article 31 referral, final outcomeEuropean Medicines Agency · European Union · dated 2024-06-26 · accessed 2026-07-31 · source 5
Direct Healthcare Professional Communication (DHPC): hydroxyprogesterone caproate (17-OHPC)-containing medicinal products — suspension of marketing authorisationsEuropean Medicines Agency · European Union · accessed 2026-07-31 · source 6

Brand names by country

Single-ingredient hydroxyprogesterone caproate names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.

Priority countries

United States

Makena (and generic hydroxyprogesterone caproate injection equivalents) (1) (2)withdrawn indication no longer marketable · 250 mg/mL · Covis Pharma (brand); multiple generic ANDA holders
Hydroxyprogesterone Caproate Injection, USP (separate ANDA — oncology/gynecologic indication) (4)current active label · 250 mg/mL, other product-dependent strengths · See current DailyMed listing

View brands in additional countries.

European Union

Proluton Depot / Progesterone Retard Pharlon / Lentogest (5) (6)