Lupron is an example of one. To give you a better understanding of this drug classification, I’ll start with the gonadotropin-releasing hormone (GnRH). After cracking open a couple of Pharmacology books and visiting a few sites, I think I’m ready to present a very general overview.
- GnRH is a decapeptide (10 amino acids) synthesized and secreted by the hypothalamus.
- GnRH travels to the anterior pituitary and binds to its specific receptor.
- The binding results in the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
- In the ovary, LH (in conjunction with FSH) increases the production of estrogen.
- Elevated levels of estrogen in the blood inhibit GnRH, LH, and FSH (negative feedback loop).
So, GnRH causes the release of LH and FSH. LH and FSH cause estrogen production. High estrogen inhibits GnRH, LH, and FSH. Got it.
Now, what the heck is a GnRH agonist?
Using leuprolide (Lupron) as the example, a gonadotropin-releasing hormone agonist binds to that specific GnRH receptor on the anterior pituitary. Lupron is a nonapeptide (9 amino acids) created in such a way that it actually binds to the receptor better than GnRH.
- This initially causes an increase in secretion of LH and FSH which stimulates estrogen production causing a temporary increase in estrogen during the first 2 weeks of treatment.
- Because the GnRH agonist is bound to the receptor already, you don’t get the LH and FSH secretion caused by receptor binding.
- Low or no LH/FSH eventually leads to low or no estrogen production.
The result is prolonged suppression (hypogonadism). Decreased estrogen may lead to hot flashes and sweats, headaches, depression, diminished libido, generalized pain, vaginal dryness, and breast atrophy.
I’ve included some links if you are interested in more information:
Luteinizing and Follicle Stimulating Hormones
(illustration of control of gonadotropin secretion)
Control of Endocrine Activity
(good section on feedback control of hormone production)
What does all of this hormone regulation stuff mean?
The lower your estrogen level falls, the more therapeutic benefit you will receive (periods stopping completely and/or fibroid shrinkage). Also remember that the lower your estrogen level falls, the higher your risk of side effects and the longer it will take for your estrogen level to rise post-treatment. It really is risk vs. benefit. Gonadotropin-releasing hormone agonists are good but not perfect. Estrogen production is not a light switch. Taking a drug will just not easily shut it off in every individual. Think more in terms of a dimmer switch. Remember that bell curve I discussed a few posts back? Most patients fall under the bell.