Editorial note: this article summarises published research on hCG, Kisspeptin-10, follitropin alfa and triptorelin. Baclabs does not sell these compounds or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.
hCG (human chorionic gonadotropin) is one of the few compounds in the peptide world with a long-established medicines licence, a Summary of Product Characteristics (SmPC) and decades of use in fertility clinics. It is also frequently reconstituted: Pregnyl comes as a 5,000 IU powder with a 1 mL solvent ampoule, and the prescribed dose is often a fraction of that.
This article places hCG alongside the other agents that act on the hypothalamic-pituitary-gonadal (HPG) axis: Kisspeptin-10, the upstream signal that drives gonadotropin-releasing hormone (GnRH); follitropin alfa (Gonal-F), the recombinant follicle-stimulating hormone (FSH); and triptorelin acetate, the GnRH agonist that switches the axis off. It sits within the specialized peptides cluster.
The HPG axis in one paragraph
Kisspeptin neurones in the hypothalamus release kisspeptin, which triggers pulsatile GnRH secretion. GnRH acts on the pituitary to release luteinising hormone (LH) and FSH. In men, LH drives testosterone production by Leydig cells and FSH supports spermatogenesis in the Sertoli cells. In women, FSH recruits and grows ovarian follicles and the mid-cycle LH surge triggers ovulation. Each drug below intervenes at one level: hCG mimics LH, Gonal-F replaces FSH, Kisspeptin-10 stimulates GnRH release, and triptorelin, after an initial surge, desensitises the GnRH receptor and shuts the axis down.
Human chorionic gonadotropin: licensed uses
Chorionic gonadotropin is a placental glycoprotein that binds the LH receptor with a longer half-life than LH itself. Pregnyl (urinary hCG) and Ovitrelle (recombinant choriogonadotropin alfa) are both prescription-only medicines.
The Pregnyl 5,000 IU SmPC lists the following indications and doses [1]:
- Ovulation induction and follicle maturation in women: 5,000–10,000 IU to complete an FSH-containing course, and 1,000–3,000 IU two to three times within nine days after ovulation for luteal support.
- Hypogonadotropic hypogonadism in men: 1,000–2,000 IU two to three times weekly for at least three months, with FSH added if spermatogenesis does not respond.
- Delayed puberty: 1,500 IU two to three times weekly for at least six months.
- Cryptorchidism: 250–1,500 IU twice weekly for six weeks, by age.
Ovitrelle is a 250 microgram prefilled pen, roughly equivalent to 6,500 IU, given subcutaneously 24–48 hours after final follicular stimulation to trigger ovulation [2]. Listed adverse effects for hCG include injection-site reactions, ovarian hyperstimulation syndrome in women, thromboembolism and gynaecomastia in men; known or suspected sex-hormone-dependent tumours are a contraindication [1].
The use of hCG in men to maintain testicular function alongside testosterone therapy, or to restart the axis after anabolic steroid use, falls outside the licensed indications. The hypogonadotropic-hypogonadism dose above is the only SmPC figure for men.
Reconstituting a 5,000 IU hCG vial
Pregnyl’s SmPC states that the powder is reconstituted with the supplied 1 mL solvent, giving 5,000 IU/mL, and that the solution should be used immediately [1]. The US Pregnyl label takes a different approach: its solvent contains 0.9 per cent benzyl alcohol, 1 to 10 mL may be added to the powder, and the reconstituted solution may be kept refrigerated for up to 60 days [7]. The single-use SmPC approach suits a single 5,000 IU ovulation trigger. When a prescriber specifies 500 IU or 1,000 IU doses several times a week, the vial must be divided, and 500 IU from a 5,000 IU/mL solution is 0.1 mL, hard to measure accurately. Clinics therefore reconstitute in a larger volume of preserved diluent. The formula is:
Concentration (IU/mL) = 5,000 IU ÷ diluent volume (mL). On a U-100 insulin syringe, 100 units = 1 mL, so each unit = concentration ÷ 100.
| Diluent added | Concentration | IU per unit (U-100) | Units for 250 IU | Units for 500 IU | Units for 1,000 IU |
|---|---|---|---|---|---|
| 1 mL (supplied solvent) | 5,000 IU/mL | 50 IU | 5 | 10 | 20 |
| 2 mL | 2,500 IU/mL | 25 IU | 10 | 20 | 40 |
| 2.5 mL | 2,000 IU/mL | 20 IU | 12.5 | 25 | 50 |
| 5 mL | 1,000 IU/mL | 10 IU | 25 | 50 | 100 |
Worked example: 5,000 IU + 5 mL bacteriostatic water = 1,000 IU/mL. Each unit on a U-100 syringe is 10 IU, so 50 units delivers 500 IU. Choose a volume that puts the dose in the 10–50 unit range; note that 5 mL exceeds the capacity of some vials, in which case 2–2.5 mL is the ceiling.
Any hCG vial that will be drawn from more than once needs a preserved diluent. Bacteriostatic water contains 0.9 per cent benzyl alcohol and is suitable for multi-dose use for up to 28 days after first puncture; unpreserved sterile water is for single use, as explained in bacteriostatic vs sterile water. Keep the reconstituted vial at 2–8°C and label it with the date of first puncture; the storage guide covers the 28-day rule. Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials; see the reconstitution guide and the dedicated hCG and fertility-medication reconstitution article for the full method. Dividing a licensed product this way is outside its SmPC and should follow the prescribing clinic’s instructions.
Kisspeptin-10: the upstream signal
Kisspeptin-10 is the ten-amino-acid C-terminal fragment of the KISS1 gene product and the shortest form that fully activates the KISS1R receptor on GnRH neurones. Its human physiology has been mapped largely by the Imperial College group of Waljit Dhillo and Channa Jayasena, and by George and colleagues in Edinburgh.
George et al. gave healthy men intravenous boluses of 0.01–3 mcg/kg and continuous infusions. A 1 mcg/kg bolus raised LH from 4.1 to 12.4 IU/L; a 22.5-hour infusion at 4 mcg/kg/h raised mean LH from 5.5 to 20.9 IU/L and testosterone from 16.6 to 24.0 nmol/L; a lower 1.5 mcg/kg/h infusion increased LH pulse frequency from 0.7 to 1.0 pulses per hour. No adverse effects were recorded [3]. Jayasena et al. then showed marked sexual dimorphism: LH and FSH rose in men at intravenous doses as low as 0.3–1 nmol/kg, and in women in the preovulatory phase, but follicular-phase women showed no gonadotropin response even at 32 nmol/kg subcutaneously or a 720 pmol/kg/min infusion [4].
Those are physiology studies in volunteers, not treatment trials. Kisspeptin-10 has no marketing authorisation anywhere. Its clinical interest is as a more physiological ovulation trigger than hCG and as a diagnostic probe of the axis. Doses reported online for “kisspeptin protocols” are not derived from any licensed regimen; the trial doses above, given intravenously under monitoring in single sessions, are the only human data.
Follitropin alfa (Gonal-F) and triptorelin
Follitropin alfa is recombinant human FSH. The EU product information licenses Gonal-F for anovulation resistant to clomifene (starting at 75–150 IU daily), for multifollicular stimulation in assisted reproduction (150–225 IU daily from cycle day 2–3, up to 450 IU in poor responders), and for stimulating spermatogenesis in men with hypogonadotropic hypogonadism at 150 IU three times weekly alongside hCG for at least four months [5]. It comes as a 75 IU powder vial and as 450 IU and 1,050 IU multidose presentations that, once reconstituted, are stable for 28 days at or below 25°C [5].
Triptorelin acetate (Gonapeptyl Depot 3.75 mg, given every 28 days) is a GnRH agonist. Continuous receptor stimulation first causes a flare in testosterone or oestrogen and then, within weeks, near-complete suppression. It is licensed for hormone-dependent prostate cancer, endometriosis, uterine fibroids and central precocious puberty; hot flushes, loss of libido, mood change and around 1 per cent monthly bone-density loss during six-month courses are the main effects [6]. In IVF, GnRH agonists prevent a premature LH surge. Triptorelin is prescription-only and a depot suspension, not a reconstituted peptide in the usual sense. The other endocrine-acting peptides in this cluster, including oxytocin, are covered in the immune and systemic regulators article.
Frequently asked questions
Is hCG a prescription-only medicine in the UK?
Yes. Pregnyl and Ovitrelle are prescription-only medicines with licensed indications in ovulation induction, luteal support, male hypogonadotropic hypogonadism, delayed puberty and cryptorchidism [1][2]. Products sold without prescription online are unlicensed supply, often stored without the refrigeration the SmPC requires, and may not contain what the label states.
How much bacteriostatic water for 5,000 IU hCG?
It depends on the intended dose. 1 mL gives 5,000 IU/mL (50 IU per U-100 unit); 2 mL gives 2,500 IU/mL (25 IU per unit); 5 mL gives 1,000 IU/mL (10 IU per unit). Pick a volume that puts the dose between roughly 10 and 50 units on the syringe, and use a preserved diluent if the vial will be drawn from more than once.
What does Kisspeptin-10 do in men?
In controlled studies in healthy men, intravenous Kisspeptin-10 raised LH within minutes and, given as a prolonged infusion, raised testosterone from 16.6 to 24.0 nmol/L [3]. It is an investigational tool with no licensed product; there is no approved regimen and no data on repeated subcutaneous use outside research settings.
What is the difference between hCG and Gonal-F?
hCG acts on the LH receptor: it triggers ovulation and, in men, drives Leydig-cell testosterone. Gonal-F is recombinant FSH: it grows ovarian follicles and supports sperm production. In male hypogonadotropic hypogonadism the SmPC combines them, 150 IU Gonal-F three times weekly with hCG, for at least four months [5].
Why does triptorelin raise testosterone before lowering it?
Triptorelin is a GnRH agonist. The first exposure stimulates the pituitary and produces a transient rise in LH and testosterone (the flare). Continuous stimulation then desensitises the receptor, and within a few weeks testosterone falls to castrate levels, which is the therapeutic aim in prostate cancer [6].
References
- Pregnyl 5000 IU, powder and solvent for solution for injection: Summary of Product Characteristics. Health Products Regulatory Authority (Ireland), 2018
- Ovitrelle 250 micrograms/0.5 ml prefilled pen: Summary of Product Characteristics. emc, medicines.org.uk
- Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men. George JT, Veldhuis JD, Roseweir AK et al. Journal of Clinical Endocrinology and Metabolism, 2011
- Effects of Kisspeptin-10 on Reproductive Hormone Release Show Sexual Dimorphism in Humans. Jayasena CN, Nijher GMK, Comninos AN et al. Journal of Clinical Endocrinology and Metabolism, 2011
- GONAL-f (follitropin alfa): EPAR Product Information. European Medicines Agency
- Gonapeptyl Depot 3.75 mg powder and solvent for suspension for injection: Summary of Product Characteristics. emc, medicines.org.uk
- Pregnyl (chorionic gonadotropin for injection) Prescribing Information. FDA, 2023
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.