Follicle-stimulating Hormone

Folitropina FSH.

ATC Vet — QG03GA90.

Follitropin Alfa

Drug Approvals

(British Approved Name, rINN)

Folitropin Alfa; Folitropina alfa; Follitropine Alfa; Follitropinum Alfa.

Фоллитропин Альфа

Follitropin Beta

Drug Approvals

(British Approved Name, rINN)

Folitropin Beta; Folitropina beta; Follitropine Bêta; FollitropinumBeta; Org-32489.

Фоллитропин Бета

Units

80 units of human pituitary follicle-stimulating hormone are contained in about 4.17micrograms (with 5 mg of mannitol and 1 mg human serum albumin) in one ampoule ofthe first International Standard (1986). 138 units of recombinant human follicle-stimulating hormone for bioassay are contained in one ampoule of the first International Standard (1995).

Adverse Effects and Precautions

As for Human Menopausal Gonadotrophins.

Spongiform encephalopathies

In a few countries, gonadotrophins derived from cadaver pituitary glands have been used in the treatment of infertility, and a small number of patients are reported to have acquired Creutzfeldt-Jakob disease from such preparations.^l However, most countries have preferred to use gonadotrophins derived from urine, and these in their turn are being replaced with recombinant products such preparations appear to carry negligible risk of transmitting prion disease.

Pharmacokinetics

Follitropins alfa and beta are slowly absorbed after subcutaneous or intramuscular injection, with an absolute bioavailability of about 70 to 80%. Peak plasma concentrations of follitropin beta have been stated to occur about 12 hours after subcutaneous or intramuscular injection. Accumulation occurs with repeated doses, reaching a steady state within 3 to 5 days. Follitropins are slowly eliminated from the body, with a terminal half-life ranging from 12 to 70 hours. About one-eighth of a dose of follitropin alfa is reported to be excreted in the urine.

Uses and Administration

Follicle-stimulating hormone is secreted by the anterior lobe of the pituitary gland, with another gonadotrophin, luteinising hormone. These gonadotrophins stimulate the normal functioning ofthe gonads and the secretion of sexhormones in both men and women. In women, follicle-stimulating hormone stimulates the development and maturation ofthe follicles and ova in men it has a role in sperma-togenesis.

Recombinant human follicle-stimulating hormones (follitropins alfa or beta) are used in the treatment of female infertility due to anovulation, in women who have not responded to clomifene therapy. Follitropins are also used for the stimulation of spermatogenesis in the management of male infertility caused by hypogonadotrophic hypogonadism (see Infertility). The dosage and schedule of treatment for female infertility must be determined according to the needs of each patient it is usual to monitor response by studying the patient’s urinary oestrogen excretion or by ultrasonic visualisation of follicles or both. In menstruating patients treatment should be started within the first 7 days ofthe menstrual cycle.

Treatment is usually begun with 75 to 150 units daily by subcutaneous or intramuscular injection for 7 or 14 days if there is no response, dosage is increased at 7- or 14-day intervals until an adequate but not excessive response is achieved.

Treatment is then stopped and followed after 1 or 2 days by a single dose of chorionic gonadotrophin 5000 to 10 000 units to induce ovulation.

It has been suggested in UK licensed product information for follitropin alfa that a daily dose of 225 units is the usual maximum, and that if a patient fails to respond adequately after 4 weeks of treatment that cycle should be abandoned and the patient should subsequently begin the next cycle at a higher starting dose. Follitropins are also used as part of IVF or other assisted reproductive technologies.

For this purpose doses of 150 to 225 units daily are generally given, for at least 4 days, commencing on the second or third day ofthe menstrual cycle. Thereafter the dose may be adjusted individually based on ovarian response to a usual maximum of about 450 units adequate follicular development generally occurs within about 5 to 10 days of treatment.

Pituitary downregulation with a gonadorelin analogue may be used with follitropin therapy, in which case the gonadorelin analogue is generally begun about 2 weeks before follitropin, and the 2 are then continued together until follicular development is adequate.

A single dose of up to 10 000 units of chorionic gonadotrophin is then given to induce final follicular maturation and oocyte retrieval performed about 35 hours later.

Follitropins are used for the stimulation of spermatogenesis in the management of male infertility caused by hypogonadotrophic hypogonadism. Before starting follitropin therapy, chorionic gonadotrophin is given to raise serum testosterone concentrations to the normal range, which may take 3 to 6 months. A dose of follitropin alfa or beta of 150 units subcutaneously three times weekly is then used, with continued chorionic gonadotrophin doses of follitropin alfa up to 300 units three times weekly may be required. Treatment is continued for at least 4 months, and more than 18 months of treatment may be needed. A dose of follitropin beta 75 units daily or two or three times weekly, by subcutaneous or intramuscular injection, has been used similarly.

Other substances with follicle-stimulating activity are used similarly: these include human menopausal gonadotrophins, which have both luteinising and follicle-stimulating activity, and urofollitropin.

Preparations

Proprietary Preparations

 

Argentina: Gonal Puregon

Australia: Gonal Puregon

Austria: Gonal Puregon

Belgium: Gonal Puregon

Brazil: Gonal Puregon

Canada: Gonal Puregon

Chile: Gonal-F Puregon

Czech Republic: Gonal Puregon

Denmark: Gonal Puregon

Finland: Gonal Puregon

France: Gonal Puregon

Germany: Gonal Puregon

Greece: Gonal Puregon

Hong Kong: Gonal Puregon

Hungary: Gonal Puregon

India: Gonal

Indonesia: Gonal Puregon

Ireland: Gonal Puregon

Israel: Gonal Puregon

Italy: Gonal Puregon

Malaysia: Gonal Puregon

Mexico: Gonal Puregon

The Netherlands: Gonal Puregon

Norway: Gonal Puregon

New Zealand: Gonal Puregon

Philippines: Gonal Puregon

Poland: Gonal Puregon

Portugal: Gonal Puregon

Russia: Gonal Puregon

South Africa: Gonal Puregon

Singapore: Gonal Puregon

Spain: Gonal Puregon

Sweden: Gonal Puregon

Switzerland: Gonal Puregon

Thailand: Gonal Puregon

Turkey: Gonal Puregon

United Kingdom: Gonal Puregon

USA: Follistim Gonal

Venezuela: Gonal Puregon

Multi-ingredient

Czech Republic: Pergoveris

Portugal: Pergoveris

UK: Pergoveris