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Buserelin, a GnRH Agonist, is Available as a Nasal Spray Inexpensively Online

By Aly W. | First published August 26, 2018 | Last modified December 11, 2020

Abstract / TL;DR

Buserelin is a GnRH agonist which is formulated as a nasal spray for use two or three times per day. GnRH agonists are the ideal antiandrogens for use in transfeminine hormone therapy. They can completely suppress gonadal testosterone production and have essentially no side effects or risks (when used in combination with estrogen therapy to avoid sex-hormone deficiency). This is in contrast to more commonly used antiandrogenic approaches in transfeminine hormone therapy like spironolactone, bicalutamide, and cyproterone acetate, as well as high-dose estradiol monotherapy—which have efficacy, tolerability, and/or safety issues depending on the modality in question. However, GnRH agonists have historically been extremely costly and consequently inaccessible for most transfeminine people. Recently, certain Eastern European online pharmacies have started selling buserelin nasal spray very inexpensively. Because of this, GnRH agonists, for the first time, appear to be an affordable option for antiandrogen therapy for any transfeminine person.

Introduction

Buserelin, also known by its major brand name Suprefact, is a gonadotropin-releasing hormone (GnRH) agonist. These medications are powerful functional antiandrogens that are able to reduce testosterone levels to the female or castrate range (<50 ng/dL). On account of their effectiveness and selectivity, GnRH agonists—as well as antagonists—may be considered the ideal antiandrogens for use in transfeminine hormone therapy.

Buserelin is one of two GnRH agonists—the other being nafarelin—that are available in the form of a three-times-a-day (once every 8 hours) nasal spray. This is an alternative means of administration relative to the typical and more invasive GnRH agonist routes of injection and implant. The use of GnRH agonists and antagonists in transfeminine people has traditionally been limited by their high costliness, which is typically upwards of US$10,000 per year.

However, buserelin has recently become available very inexpensively online from a number of Eastern European online pharmacies. The first such pharmacy was known as Cherry Pharmacy (Reddit; Reddit; Reddit; Reddit; Reddit). They sold buserelin nasal spray here (180 × 150-μg doses for US$29.60) and here (140 × 150-μg doses for US$28.50). Buserelin stopped being purchasable from Cherry Pharmacy by February 2019 and the site is now defunct (Reddit; Reddit; Reddit; Reddit; Reddit; Reddit). But other online pharmacies have since began selling inexpensive buserelin nasal spray as well and as of February 2020 the product is available from these sources (Reddit; Reddit; see also the comments). hrt.cafe maintains a listing of online pharmacies that sell buserelin and other GnRH agonists.

Dosage and Effectiveness

Dosage information for buserelin nasal spray is as follows (Wiki; see page for sources):

For prostate cancer, the dosage of buserelin by subcutaneous injection is 500 µg three times per day (once every 8 hours, 1,500 µg/day total) for one week and then 200 µg once daily thereafter. If buserelin is used as a nasal spray, the dosage for prostate cancer is 800 µg sprayed into the nostrils three times per day (once every 8 hours, 2,400 µg/day total) for one week followed by 400 µg sprayed into the nostrils three times per day (once every 8 hours, 1,200 µg/day total) thereafter. For endometriosis, buserelin is used specifically as a nasal spray and the dosage is the same as that used for prostate cancer. These dosages of buserelin for both subcutaneous injection and nasal spray have been found to decrease testosterone levels to castrate or near-castrate levels in men with prostate cancer, although suppression was more complete with subcutaneous injection presumably due to suboptimal absorption with intranasal administration.

And suppression of testosterone levels with different buserelin nasal spray dosing regimens is as follows (Wiki; see page for sources):

Buserelin has been found to suppress testosterone levels in men with prostate cancer from 426 ng/dL to 28 ng/dL (by 93.4%) with 200 μg by subcutaneous injection once per day and from 521 ng/dL to 53 ng/dL (by 89.8%) with 400 μg by nasal spray once every 8 hours (1,200 μg/day total). The difference in suppression may have been due to poor compliance [with the nasal spray formulation]. A few small studies have also assessed the suppression of testosterone levels with buserelin nasal spray twice a day instead of three times a day. One such study found that testosterone levels in men with prostate cancer were suppressed during treatment with buserelin from 332 ng/dL to 215 ng/dL (28.9% lower than controls) with 200 μg by nasal spray twice a day (400 μg/day total), from 840 ng/dL to 182 ng/dL (71.4% lower than controls) with 500 μg by nasal spray twice a day (1,000 μg/day total), and from 598 ng/dL to 126 ng/dL (80.4% lower than controls) with 50 μg by subcutaneous injection once a day.

Although the absorption of buserelin as a nasal spray may be suboptimal, and although buserelin nasal spray by itself may only be able to achieve near-castrate levels of testosterone (rather than the low castrate levels more typical of castration/GnRH agonists and antagonists), estrogens are also potent antigonadotropins, and it may be that if even relatively low doses of estradiol are combined with buserelin, testosterone will be more fully suppressed (into the castrate/female range (<50 ng/dL) or by 95% or more). We see this with progestogens, in which high doses are able to maximally suppress testosterone levels by 50 to 70% (to around 200–300 ng/dL on average) but combination with low doses of estrogens are able to suppress testosterone levels by around 95% or into the low castrate range (to around 20–30 ng/dL on average) (Aly W., 2019). Similar influences on testosterone levels might be expected with the combination of buserelin and an estrogen.

If for whatever reason an estrogen is not desired (e.g., if the purpose is simple puberty blockade or non-binary hormone therapy; Aly W., 2019), buserelin could alternatively be combined with low doses of a progestogen to more fully suppress testosterone levels. Or, as another alternative, buserelin could be combined with low-dose bicalutamide or spironolactone to block the actions of any testosterone that remains unsuppressed.

It’s possible to use buserelin twice a day instead of three times a day for improved convenience. However, this does appear to result in somewhat diminished effectiveness in terms of testosterone suppression (Faure et al., 1982; Tolis et al., 1983). In any case, if buserelin is combined with an estrogen or progestogen, due to the supplementary testosterone suppression that they provide, more complete suppression of testosterone levels may still be achieved and hence the reduced effectiveness of twice-daily buserelin might not be that consequential.

It should be noted that the Cherry Pharmacy buserelin nasal sprays contain 150 μg buserelin per spray, whereas the dosage information above assumes that the nasal spray can deliver an even 400 μg in sprays per dose. Obviously, this isn’t possible with a nasal spray that delivers 150 μg per spray. Instead, such a product could be used to provide 300 μg per dose (two sprays) or 450 μg per dose (three sprays). If buserelin is combined with an estrogen or a progestin, which will help suppress testosterone levels, it might be optimal to go with the former lower buserelin amount of 300 μg per dose (two sprays). Conversely, if buserelin is not combined with a supplemental antigonadotropin, the latter higher buserelin amount of 450 μg per dose (three sprays) may be advisable. Alternatively, a user could administer a mix of 450 μg for the first dose, 300 μg for the second dose, and 450 μg for the third dose each day to achieve an even daily dosage of 1,200 μg per day (which would be equivalent to 400 μg three times per day and in line with the buserelin dosage information listed above).

Dosing Regimens and Costs

The costs of the buserelin nasal sprays from Cherry Pharmacy, dosed the recommended three times per day and not including tax or shipping and handling, break down as follows:

Bottle versionDoses each dayaTotal per dayBottle will last…Cost per 30 days
180x 150-μg doses300 μg, 300 μg, 300 μg900 μg30 daysUS$29.60
 450 μg, 300 μg, 450 μg1,200 μg22.5 daysUS$39.47
 450 μg, 450 μg, 450 μg1,350 μg20 daysUS$44.40
140x 150-μg doses300 μg, 300 μg, 300 μg900 μg23.3 daysUS$36.64
 450 μg, 300 μg, 450 μg1,200 μg17.5 daysUS$48.86
 450 μg, 450 μg, 450 μg1,350 μg15.6 daysUS$54.96

a One dose administered every 8 or so hours, 3 times per day in total.

The most inexpensive route would be the US$29.60 option, whereas the best balance between cost and efficacy would probably be the US$39.47 option. If one were to do twice a day administration of buserelin, a regimen of 600 μg in the morning and 600 μg in the evening (12-hour separation), for a total dosage per day of 1,200 μg, might be optimal. This is the same total daily dosage as the US$39.47 option, and hence would be the same cost.

The preceding cost information is now obsolete as Cherry Pharmacy is defunct. However, other sources of buserelin nasal spray may have similar pricing and hence it may still have some relevance.

Initiation of Therapy

Buserelin nasal spray requires a higher dosage during the first week of therapy. In addition, GnRH agonists cause a testosterone flare during the first week of treatment that returns to around baseline by the end of that week Some more information (Wiki). It takes about 2 to 4 weeks for GnRH agonists to reduce testosterone levels to the female or castrate range Some more information (Wiki). These specifics should be kept in mind when using buserelin nasal spray as well as other GnRH agonists. The following passage provides more detail on the early dynamics of testosterone suppression with GnRH agonists and antagonists (Wiki; see page for sources):

There are two types of GnRH modulators: GnRH agonists and GnRH antagonists. These medications have the opposite action on the GnRH receptor but paradoxically have the same therapeutic effects. GnRH agonists, such as leuprorelin (Lupron), goserelin (Zoladex), and buserelin (Suprefact), are GnRH receptor superagonists, and work by producing profound desensitization of the GnRH receptor such that the receptor becomes non-functional. This occurs because GnRH is normally released in pulses, but GnRH agonists are continuously present. At the initiation of treatment, GnRH agonists are associated with a “flare” effect on hormone levels due to acute overstimulation of the GnRH receptor. In men, [luteinzing hormone (LH)] levels increase by up to 800% while testosterone levels increase to about 140 to 200% of baseline. Gradually however, the GnRH receptor desensitizes; testosterone levels peak after about 2 to 4 days, return to baseline after about 7 to 8 days, and are reduced to castrate levels within 2 to 4 weeks. Antigonadotropins such as estrogens and cyproterone acetate can be used to diminish or prevent the testosterone flare caused by GnRH agonists. In contrast to GnRH agonists, GnRH antagonists, such as degarelix (Firmagon) and elagolix (Orilissa), work by binding to the GnRH receptor without activating it, thereby displacing GnRH from the receptor and preventing its activation. Unlike with GnRH agonists, there is no initial surge effect with GnRH antagonists, and the therapeutic effects are immediate; sex hormone levels are reduced to castrate levels within a few days.

Discussion and Conclusions

GnRH agonists and antagonists are the ideal antiandrogens for use in transfeminine hormone therapy. They are the most effective, best-tolerated, and safest antiandrogens that are currently available. One could conceptualize them essentially as a readily reversible orchiectomy and little else. When used in combination with an estrogen they have none of the side effects and risks of more mainstream antiandrogens like spironolactone, cyproterone acetate, and bicalutamide and they have none of the effectiveness concerns associated with antiandrogens that act as AR antagonists like spironolactone and bicalutamide (Aly W., 2018; Aly W., 2019; Wiki). GnRH agonists and antagonists allow for the use of essentially any dosage of estradiol without having to worry about testosterone suppression. This is of particular interest in the context of mimicking the hormonal profile of female puberty (which involves low estradiol levels) to possibly optimize breast development and feminization in transfeminine people.

Access to GnRH agonists and antagonists has been limited for transfeminine people due to the high costs of these medications and the fact that medical insurance usually denies them. Thanks to the availability of inexpensive buserelin nasal spray from online pharmacies however, it would appear that a GnRH agonist is now a practical and affordable option for any transfeminine person. Provided a person doesn’t mind the inconvenience of having to use a nasal spray multiple times per day, buserelin nasal spray may be among the best available options for an antiandrogen in transfeminine people.