Human chorionic gonadotropin (hCG) and women: features and risks

For the female body, human chorionic gonadotropin (hCG) is not a foreign substance but a natural pregnancy hormone. That is precisely why its pharmacological use in women has an entirely different meaning than in men: here it works as a tool of reproductive medicine rather than as a means of "supporting" the testes. At the same time, the risks in women are specific and sometimes serious. The editorial team explains the particulars and where the limits of safety lie.

hCG in female physiology

hCG is naturally produced by the cells of the trophoblast — the future placenta — shortly after the embryo implants. Its main task in early pregnancy is to sustain the corpus luteum, which produces progesterone, until the placenta takes over that function. Without hCG the corpus luteum regresses and menstruation follows.

The hCG level rises quickly in early pregnancy, peaking at the end of the first trimester and then declining. Pregnancy tests are based precisely on detecting this hormone. The review by Cole (2010) describes several forms of hCG — including a hyperglycosylated variant important for implantation — with different biological functions.

Outside of pregnancy, hCG is almost undetectable in the blood of a non-pregnant woman. Its appearance may indicate pregnancy (including ectopic), trophoblastic disease or, more rarely, hormone-producing tumors. For this reason, any detection of hCG without an obvious cause warrants investigation.

Pharmacological hCG acts on the same LH/hCG receptors as the endogenous hormone. In the ovary it stimulates theca and granulosa cells and can trigger the rupture of a mature follicle — ovulation. This property underlies its medical use.

Medical use in women

The main indication is infertility treatment. hCG is used as an ovulation "trigger" after stimulation of follicle growth, for the final maturation of oocytes before retrieval in IVF programs, and in certain protocols to support the luteal phase. The ESHRE guideline (2020) treats the choice of trigger and its timing as one of the key stages of stimulation.

hCG exists in two main forms: the urinary form, obtained from the urine of pregnant women, and recombinant choriogonadotropin alfa. They share the same active molecule but differ in the degree of purification, dosing in units or micrograms, and presentation. The choice depends on the protocol and the clinic.

It is important that the timing of the "trigger" injection is determined from ultrasound and hormone data — an injection given too early or too late reduces the chances of success. That is why, even in a medical context, hCG is not a "standalone" drug but part of a carefully controlled regimen.

Outside reproductive medicine there are essentially no justified indications for hCG in women. Its use for weight loss or "rejuvenation" is not supported by evidence.

Specific risks: OHSS, multiple pregnancy, ectopic pregnancy

The best-known serious risk is ovarian hyperstimulation syndrome. It develops when the ovaries enlarge in response to stimulation and the blood vessels begin to leak fluid into the abdominal cavity. Mild forms present with bloating and discomfort; severe forms with ascites, shortness of breath, hemoconcentration, thrombosis and impaired kidney function. The ASRM guidelines (2016) describe the prevention and treatment of this condition.

The risk of OHSS is higher in young women, in polycystic ovary syndrome, with high AMH levels and a large number of follicles. The onset of pregnancy aggravates the syndrome, because the embryo's own hCG continues to stimulate the ovaries. That is why, in high-risk groups, alternative triggers are used or embryos are frozen.

The second risk is multiple pregnancy. If several follicles have matured at the time hCG is administered, several eggs may ovulate. Multiple pregnancy increases the risks for both mother and children: preterm birth, preeclampsia, gestational diabetes. That is why, when there are too many follicles, the physician may cancel the trigger.

Ectopic pregnancy is also somewhat more common in women being treated for infertility, and early confirmation of the location of the gestational sac is a mandatory part of monitoring. The prescribing information for hCG products also mentions the risk of thromboembolic events, especially in women with risk factors.

The "hCG diet": the weight-loss myth

The "Simeons diet", popular among women, deserves separate attention — a combination of hCG injections or drops with a very low-calorie diet. Its proponents claim the hormone "burns" fat and reduces hunger. This idea appeared in the 1950s and has been tested repeatedly ever since.

The meta-analysis by Lijesen and colleagues (1995), published in the British Journal of Clinical Pharmacology, found no evidence that hCG promotes weight loss, fat redistribution or reduced hunger beyond the effect of the low-calorie diet itself. Weight loss in such programs is explained precisely by the sharp restriction of calories.

Regulatory authorities, in particular the FDA in the United States, have repeatedly warned about over-the-counter "homeopathic" hCG weight-loss products, which are not approved for this purpose and often contain no meaningful amount of the hormone. A very low-calorie diet without supervision, in turn, carries its own risks — gallstones, loss of muscle mass, electrolyte disturbances.

• hCG is not approved as a weight-loss agent.
• The effect of such programs is explained by the calorie deficit.
• Injections of the hormone in women outside infertility treatment can affect the cycle and the results of pregnancy tests.

Female athletes and anti-doping status

On the WADA Prohibited List, human chorionic gonadotropin and LH are prohibited specifically for men (section S2). For women they are formally not included under this heading, because in the female body hCG does not produce a significant rise in androgens and is not regarded as a performance-enhancing agent, while its natural increase is associated with pregnancy.

This does not mean that a female athlete "may" use hCG for any purpose. Medical use must be justified, and the side effects — from OHSS to menstrual disturbances — directly affect the ability to train. In addition, a positive hCG result in a woman's doping sample may prompt a medical evaluation.

Handelsman (2006) explains the logic of the ban: in men hCG stimulates testosterone production and can be used to mask androgen use and to recover afterwards. In women these mechanisms do not work the same way, which is reflected in the wording of the rules.

Female athletes who are planning pregnancy or infertility treatment should discuss all the drugs in the protocol with the team physician and the anti-doping organization in advance, since other stimulation agents, such as estrogen receptor modulators, may have a different status.

Editorial conclusions

For women, hCG is a natural pregnancy hormone, and its pharmacological use is limited to reproductive medicine: ovulation induction, IVF, and certain luteal phase support protocols.

The key risks are ovarian hyperstimulation syndrome, multiple pregnancy and thromboembolic complications. They depend on the ovarian response and are therefore monitored with ultrasound and laboratory tests.

The use of hCG for weight loss has no evidence base, and self-administered injections outside infertility treatment make no sense and carry risks.

We also recommend our articles on menotropin in women, on the tests used during the medical application of hCG, and on the myths surrounding this hormone.

References

1. Cole LA. Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol. 2010;8:102.
2. Bosch E, Broer S, Griesinger G, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open. 2020;2020(2):hoaa009.
3. Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril. 2016;106(7):1634–1647.
4. European Medicines Agency. Ovitrelle (choriogonadotropin alfa): Summary of Product Characteristics. EMA.
5. Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Br J Clin Pharmacol. 1995;40(3):237–243.
6. Handelsman DJ. Clinical review: The rationale for banning human chorionic gonadotropin and estrogen blockers in sport. J Clin Endocrinol Metab. 2006;91(5):1646–1653.
7. World Anti-Doping Agency. The World Anti-Doping Code: International Standard — Prohibited List. Montreal: WADA; актуальна редакція.