Gonadotrophins (HCG, FSH, LH)

This includes ¹:

• Chorionic Gonadotropin or Choriogonadotropin alfa (both forms of Human Chorionic Gonadotrophin)
• Follitropin alfa and beta (a recombinant form of Follicle Stimulating Hormone)
• Human menopausal gonadotrophins (a combination of follicle stimulating hormone and luteinizing hormone)
• Lutropin alfa (a recombinant form of luteinizing hormone).

Human chorionic gonadotropin (hCG) is a glycopeptide that maintains the corpus luteum at ovulation if the pregnancy is viable. If there are mature ovarian follicles these can be stimulated to ovulation by hCG. In this sense the actions of hCG are similar to leuteinizing hormone.
In practice there are two forms of hCG: Chorionic Gonadotropin and choriogonadotropin alfa. The former is obtained from urine and the latter is a recombinant version of hCG.

Indications

• Chorionic gonadotropin is usually used to assist conception once clomifene alone has not worked
• Used to aid fertility in anovulatory fertility patients who are undergoing ovulation induction ²
• In women undergoing assisted reproduction e.g. IVF - patients have hCG injection and then ova are harvested 36 hours later.
• In men chorionic gonadotropin enhances development of secondary sexual characteristics and spermatogenesis. Therefore, it is used in hypogonadotropic hypogonadism i.e. secondary hypogonadism to induce spermatogenesis and occasionally in cryptorchidism.
• In delayed male puberty therapeutic hCG stimulates endogenous testosterone production from leydig cells.

Cautions and Contraindications

• Asthma
• Seizures
• Recent ectopic pregnancy
• Ischaemic heart disease
• Renal impairment
• Migraines can be worsened
• Prostatic cancer
• Thromboembolic disease e.g. recent DVT or PE
• Precocious puberty
• Fibroid tumors or ovarian cysts
• Irregular vaginal bleeding

Side effects

• Bloating and pelvic pain in women
• Nausea, vomiting and abdominal pain
• Diarrhoea
• Difficulty in breathing
• Rapid weight gain
• Injection site reactions
• Peripheral oedema - dose may need to be reduced
• Headache
• Lethargy
• Depression and mood swings
• Gynaecomastia and breast pain
• Ovarian hyperstimulation
• In males there can be acne, growth of testes and rapid increase in height

Administration

hCG can be administered as either subcutaneous or intramuscular injections (usually the former). They have to be given in pulses at precise intervals.

Follitropin alfa is a recombinant form of follicle stimulating hormone (FSH) and its main action is to develop ova from the ovaries.

Indications

• Women who are having difficulty in conceiving in whom the main problem lies in ovulation
• Used in polycystic ovarian syndrome once clomifene and metformin have failed - this group of women tend to have excessive leuteinizing hormone and lack FSH
• May be used with therapeutic hCG in women about to undergo assisted reproduction e.g. IVF
• In men follitropin alfa will increase the number of sperm produced - they are usually pre-treated with therapeutic hCG to enhance testosterone levels which then continues until FSH therapy stops
• Some patients will be given gonadotrophin-releasing hormone before therapeutic FSH so that the release of endogenous FSH from the pituitary is shut down. This allows accurate dosing of FSH.
• Follitropin alfa has no role in patients with primary ovarian or testicular failure

Cautions and Contraindications

• Asthma
• Irregular vaginal bleeding
• Uncontrolled thyroid disease
• Adrenal disease
• Brain neoplasm
• Ovarian cysts

Side effects

• Abdominal pain - stop injections and seek advice
• Dizzy spells which may interfere with reaction times
• Nausea and vomiting
• Rapid weight gain
• Injection site reactions
• Flu-like illness
• Breast pain
• Depression and mood swings
• Migraines

Administration

These are usually self-administered as a subcutaneous injection. Injection sites should be rotated.

Lutropin alfa is a recombinant form of Luteinizing hormone. It helps patients to conceive.

Indications

Lutropin alfa is used in women who are unable to conceive and lack leuteinizing hormone e.g. in hypogonadal hypogonadism. It is usually given along with follitropin alfa.
The cautions contraindications and side effects are the same as for follitropin alfa - see above. It is also self-administered subcutaneously and sites of injection need to be rotated.

This is a combination of follicle stimulating hormone and luteinizing hormone. It was discovered in the 1970's and is extracted from the urine of menopausal women.
It encourages ovulation and is usually combined with human chorionic gonadotropin. In men human menopausal gonadotropin increases testosterone and thereby, sperm production.
The cautions, contraindications and side effects are similar as for human chorionic gonadotropin and follitropin alfa.

• In terms of fertility rates between recombinant versions and those derived from urine there appears to be no real difference ^{3 4}
• 35% of women who become pregnant after hMG or hCG will suffer a miscarriage
• Recombinant forms are more aesthetically pleasing and associated with less immunological reactions. Unsurprisingly, urine-based gonadotrophins are less expensive ^{3 4}