Lupron is a trade name for leuprorelin or leuprolide. It belongs to a family of drugs known as gonadotropin releasing hormone analogues, or GnRH analogues for short. Other members of this family include goserelin and pretty much all the other ~relin drugs.

GnRH is the hormone responsible for signalling the extent of the body's satisfaction with the current level of gonadal activity. It acts upon the pituitary to control the levels of gonadotropin production, primarily luteinizing hormone and follicle-stimulating hormone production. Hence, GnRH is a 'gonadotropin-releasing' hormone, rather than a gonadotropin itself.

By interfering with the feedback loop controlling the gonads, the brain can be prompted to cease production of gonadotropins entirely, thus halting production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn halts the production of sex hormones- namely testosterone in men, estrogen and progesterone in women. It also halts reproductive function in most men after a few months of treatment, and in all women almost immediately. It is thus used as an effective contraceptive, and as a treatment for cervical cancer, endometriosis, etcetera.

More controversially, GnRH analogues are used to chemically castrate sex offenders in some countries. It's far more successful than using Provera, which is a trade name for medroxyprogesterone acetate. Filling men with progesterone tends to cause them to kill themselves.

Since GnRH analogues and agonists only need to be present in nanogramme quantities to function effectively, the most convenient method of delivery is via a deep depot injection of a suspension consisting of coated granules of medication. Lupron and its cousin goserelin are available in a one-month-one-injection form, and a three-month-one-injection form. When used as a contraceptive, 'time off' between injections is normally used to allow the woman's skeleton to recover from calcium loss caused by lack of hormones. Alternatively, a selective estrogen receptor modulator (SERM) medication such as tamoxifen may be prescribed, to direct estrogenic molecules away from the reproductive organs and towards the skeletal receptors.

Gonadotropin-related drugs are new and as a results and applications are not fully explored. They are much more effective than the old generation of drugs such as alpha-5 reductase inhibitors and similar anti-androgen medications in preventing the synthesis of androgenic compounds. As they are administered in extremely small doses, they have few side effects.

Lupron is also available as a plastic subcutaneous implant- a sliver of plastic impregnated with the drug which will gradually dissolve over time. This is available in three-month and (I believe) six month varieties.

So why the controversy?

After complaints from consumer groups in the US, the FDA conducted a review of Lupron in 1999. They studied the side-effects experienced by 6000 Lupron users. Unfortunately, the sample was selected by interviewing people who had submitted MedWatch reports- these are like customer complaint forms- and as such, the sample was entirely self-selecting.

The top 35 adverse reactions reported by women (the main users of Lupron) were as follows: This list lifted from the National Lupron Victims Network, who lifted it from the FDA memo March 1999.

In all, there were 25 reports of death of females; obviously it is difficult to attribute these to the drug directly. The National Lupron Victims Network obviously seems to think that the drug was responsible. There were 325 reports of hospitalization of females, which is a remarkably low level of adverse effects for such a powerful drug.

The victims of Lupron are understandably aggrieved and seek to punish the drug company for what they see as a lack of proper testing; perhaps they didn't understand the drug's workings, or the possibility of side effects. Side effects exist with all drugs and noting the many tens of thousands of doses of Lupron that have been delivered, the rate of adverse effect seems quite low, especially considering the power of the drug and the complexity of its mechanism. Some of the side effects are predictable- after all, you would expect a drug designed to switch off hormone production to produce menopausal type symptoms.

Lupron has also been widely misprescribed, and this fault can only lie at the doors of the health system. We live in an era where nanogramme-quantity drugs can modify the action of dozens of biochemical pathways all over the body, but where every primary healthcare provider is licenced to prescribe any and all of them; worse still, psychiatrists with no training whatsoever in endocrinology can and do prescribe medications of almost other-worldly power such as Lupron.

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