All three hormones—FSH, LH, and hCG—are heterodimers that share an identical α subunit in addition to a distinct β subunit that confers receptor specificity. The β subunits of hCG and LH are nearly identical, and these two hormones are used interchangeably. All the gonadotropin preparations are administered by subcutaneous or intramuscular injection, usually on a daily basis. Half-lives vary by preparation and route of injection from 10 to 40 hours.
A. Menotropins
The first commercial gonadotropin product containing both FSH and LH was extracted from the urine of postmenopausal women. This purified extract of FSH and LH is known as menotropins, or human menopausal gonadotropins (hMG). From the early 1960s, these preparations were used for the stimulation of follicle development in women. The early extraction techniques were very crude, requiring around 30 L of urine to manufacture enough hMG needed for a single treatment cycle. These initial preparations were also contaminated with other proteins; less than 5% of the proteins present were bioactive. The FSH-to-LH bioactivity ratio of these early preparations was 1:1. As purity improved, it was necessary to add hCG in order to maintain this ratio of bioactivity.
B. Follicle-Stimulating Hormone
Three forms of purified FSH are available. Urofollitropin, also known as uFSH, is a purified preparation of human FSH extracted from the urine of postmenopausal women. Virtually all the LH activity has been removed through a form of immuno-affinity chromatography that uses anti-hCG antibodies. Urofollitropin was withdrawn from the US market in 2015. Two recombinant forms of FSH (rFSH) are also available: follitropin alfa and follitropin beta. The amino acid sequences of these two products are identical to that of human FSH. They differ from each other and urofollitropin in the composition of carbohydrate side chains. The rFSH preparations have a shorter half-life than preparations derived from human urine but stimulate estrogen secretion at least as efficiently and, in some studies, more efficiently. Compared with urine derived gonadotropins, rFSH preparations have little protein contamination, much less batch-to-batch variability, and may cause less local tissue reaction. The rFSH preparations are considerably more expensive.
C. Luteinizing Hormone
Lutropin alfa, the first and only recombinant form of human LH, was introduced in the United States in 2004 but withdrawn in 2012. When given by subcutaneous injection, it has a half-life of about 10 hours. Lutropin has only been approved for use in combination with follitropin alfa for stimulation of follicular development in infertile hypogonadotropic hypogonadal women with profound LH deficiency (<1.2 IU/L). Lutropin alfa with follitropin alfa may also be of benefit in certain subgroups of normogonadotropic women (eg, those with an inadequate response to prior follitropin alfa monotherapy). It has not been approved for use with the other preparations of FSH or for induction of ovulation.
D. Human Chorionic Gonadotropin