Tell me about Lupron, Synarel, and Zoladex (gonadotropin-releasing hormone agonists)

One upon a time (months ago), I wrote a post on gonadotropin-releasing hormone (GnRH) agonists but I don’t think anyone really saw it. I guess it’s the name. Gonadotropin-releasing hormone agonist does sound kind of strange.

How about Lupron, Synarel, and Zoladex? Yeah, still a little funny sounding but better. Lupron, Synarel, and Zoladex all belong to the class of drugs known as (everybody chime in)… gonadotropin-releasing hormone agonists (GnRH agonists).

What does that mean?
An agonist is simply something that acts like something else. In this case, Lupron, Synarel, and Zoladex act like GnRH (the natural thing in your body). Let’s look at GnRH for a moment. This is the normal chain of events in your body:

  1. GnRH is a decapeptide (10 amino acids) synthesized and secreted by the hypothalamus (in your brain).
  2. GnRH travels to the anterior pituitary (the anterior lobe of the pituitary gland located at the base of your brain) and binds to its specific receptor.
  3. The binding of GnRH to its receptor results in the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
  4. LH and FSH travel to the ovary.
  5. In the ovary, LH (in conjunction with FSH) increases the production of estrogen.
  6. Elevated levels of estrogen in the blood inhibit the secretion of GnRH, LH, and FSH (negative feedback loop).

What’s a negative feedback loop?
Think in terms of the furnace in your house. From Control of Endocrine Activity:

When the furnace produces enough heat to elevate temperature above the set point of the thermostat, the thermostat is triggered and shuts off the furnace (heat is feeding back negatively on the source of heat). When temperature drops back below the set point, negative feedback is gone, and the furnace comes back on.

So normally in your body, GnRH causes the release of LH and FSH. LH and FSH cause estrogen production. High estrogen inhibits GnRH, LH, and FSH. Got it.

Well then, what the heck is a GnRH agonist?
Let’s look at the amino acid structures first.

Here is GnRH that is in your body naturally:


Lupron (leuprolide):


Synarel (nafarelin):


*D-Nal = D-3-(2-naphthyl)-alanine

Zoladex (goserelin):


See how they’re actually quite similar? Just a couple of amino acids are changed. These changes cause Lupron, Synarel, and Zoladex (GnRH agonists) to bind to the GnRH receptor in the anterior pituitary better than your naturally occurring GnRH. The substitutions also inhibit rapid degradation (the agonists stay around a little longer).

GnRH agonists bind to the receptors so well that…

  1. This initially causes an increase in secretion of LH and FSH.
  2. This stimulates estrogen production causing a temporary increase in estrogen during the first 2 weeks of treatment.
  3. Because the GnRH agonist is bound to the receptor already, you don’t get the LH and FSH secretion caused by receptor binding.
  4. Low or no LH/FSH eventually leads to low or no estrogen production.

Side effects: 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.

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 not just 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.

Why does it take so long for the side effects to go away?
It can take several weeks for the GnRH agonist to “clear” your body. Think about a monthly shot for example. A therapeutic level of the drug will be in your body for at least a month after your last injection. Once the GnRH agonist is gone, it will still take some time before your estrogen level rises. Remember that you have to return to your normal pattern. Your natural GnRH has to be produced and secreted. It binds to the receptor and LH/FSH is produced and secreted. LH and FSH both travel to the ovary and increase estrogen production. Just like much in life, it’s a process.


Related Post:
How are you feeling after your Lupron injections? Any side effects?


39 Responses to “Tell me about Lupron, Synarel, and Zoladex (gonadotropin-releasing hormone agonists)”

  1. malexmom Says:

    Here’s my question…… I can see the that the chemical structure of Lupron, Synarel, and Zoladex are very similar – my Dr. has just recomended 4 months of Lupron injections and I’ve been reading all the scary side effects (good point about people with negative experiences being more motiviate to blog – I’m keeping that in mind!) of this treatment. What are the differences between these medications in terms of their side effects – I understand that they are all there to induce temporary menopause so those symptoms are all the same, but is one better than another for mood issues, headaches, etc? I also remember reading somewhere else on this site that there is an inhaled version of this treatment that may not hit your system as hard. Quite curious to know what other people have heard/experienced. Thanks!

  2. nic Says:

    I started a course of Synarel which was taken by nasal inhalation a few years back but I stopped because I felt “not myself” on it. I didn’t give it a chance to start working properly I guess but I know I’m one of those types who is extremely sensitive to taking artificial hormones & this has no doubt turned me psychologically against them. At the end of the day, my symptons weren’t bad enough for me to want to continue with hormonal treatment, given my view of them. I believe Synarel is the mildest. One thing I also found weird was that I had to administer it to myself & because I felt that effectively it was harming me, I hated it & probably wasn’t doing it correctly either. It was quite awkward to take nasally too. However if you have a positive view of taking it you will probably lap it up!
    I don’t think that has answered your particular question malexmom, just my 2 cents worth!

  3. Sunday Says:

    Hi. I took Synarel nasal spray and it worked a treat and shrank my fibroid significantly. Once the drug had built up in my system, I felt ok. For the first few weeks of taking the spray (two sprays daily, morning and night), I had some headaches. I negotiated with my gyn to build up the drug slowly by starting off with just one spray per day for two weeks, building up the the full dose of two sprays after the fortnight (this was for my own comfort and made me feel more relaxed about taking the drug, don’t know if it helped medically or not, but psychologically was a good move). I was also slightly vague whilst on the drug, but not significantly; a little like when you are pregnant. But I was feeling ok most of the time, continued working, and looked after our three children; all the normal stuff and I was pleasantly surprised because, like you I had read horror stories and was expecting a nasty couple of months. Not so, and worth it-I liked the control of administering the drug myself.

  4. Sunday Says:

    OH one other thing, my libido was zilch, a downer I know, but you don’t miss it when you don’t want it, but my poor husband!!

  5. malexmom Says:

    Nicand Sunday,

    Thanks so much for your input. I get my first of four Lupron injections on Friday (the one month kind). I asked about the inhaled version, but was told by my gyn. that she had never really heard of that and that it might be an “outmoded” therapy.

    • coco77385 Says:

      My Doctor also told me she hadn’t heard of it but I faxed the information to her and she agreed it would be a better choice for me. I hate needles and the expense if the shot would have been too much for me. The nasal spray was actually covered by insurance.

  6. Katharine Says:

    Dear Malexmom,
    My doctor wants to give me Lupron injections for a few months so that we can do laparascopic surgery (leaving cervix and ovaries). How are you reacting to the injections?

  7. brenda smith Says:

    Hello there I am starting Lupron injections in the next week or so as well. I am very nerous but I have to do something to get rid of these fibroids. Maybe we can compare notes on side effects and/ or results. Good luck!! I am trying to think posotively.

  8. Alison Says:

    Hi, I’ve just finished a course of Decapeptyl which seems to be the European version of Lupron. I didn’t know what to expect when I started my course, read up on the side effects but was still a bit scared by it all so I know how you all feel. What I have have found is that the first 2 months were the hardest and then i just seemed to climb that peak and it’s been a lot better since. First 2 months – hot flashes, some mood swings but not so bad, headaches, a lot of fatigue and general muscular aches and pains, some bloating and water retention as well, often felt quite sad (not depression, but a kind of sadness that was definitely hormonal). The last 2 months – hot flashes have continued, but tiredness and aches and pains have gone etc and have felt a lot more energy than I have in 2 or 3 years and do, honestly feel I’m improving. Had scan done a few weeks ago and there has so far been just a slight change in size of the largest fibroid (17cm) so it’s to be reviewed again in 2-3 months as doctor feels it may be taking a bit longer to work for me, and especially as the fibroid is so large. I do feel it’s getting smaller, and have a lot more energy than I used to have so that’s a major positive.
    So if you are starting injections, try to be positive and focus on the end result – it has been tough for me but I do feel it’s been worth it !

  9. Jeanel Says:

    I’m sorry I don’t have an answer for you, just another question for the world.

    I had decapeptyl for 5 months in 2001 as a pre-op treatment. I had a pretty rough time with it but not as bad as with the depo-progevera (progesterone) they gave me afterwards.

    In 2004 I had a beautiful clean uterus but my intestines were covered in fibroids. It’s called Leiomiomatosis Peritonealis Diseminada. They were estrogen receptor negative but progesterone positive. Good thing I didn’t self-medicate with progesterone cream! They operated and took the miomas (fibroids) out as well as my stony gallbladder.

    Now they are back and going for the liver. One Dr. suggested the monthly Decapeptyl shot again but with add-back hormones. My understanding is that it shouldn’t be taken more than once in a life time or for more than 6 months because of the neurological and bone density risks. I’ve found one study about it with add-back but even that says only up to a year.

    I have lost confidence in the system and would rather risk living with my tumors but would still like to know.

    So my questions for the wise ones out there are: How long can a GnRH analog be taken with add-back?

  10. Jeanel Says:

    By the way, for me, living with one big uterine grapefruit was much worse than living with 50 intestinal tangerines. Vaginal dryness and clitoral shrinkage still in effect.

  11. looking for answers Says:

    I was diagnosed with endometriosis in the late 80’s. After laproscopic surgery, (1990) I began a six month dose of Synarel with HrT (Premarin). After the six months, time went by until I was once again put on Synarel only this time with no HrT and had to take the dose 3 times a day. I have since developed an adenoma pitituary tumor (removed successfully thank God). I am trying to determine if there is any relation to the Synarel and the tumor. Does anyone have any information that may be of help to me in my search for answers? (I am not looking for litigation. I would just like to know, if possible, how this occurred and why.)

    • Eva George Says:

      I don’t know if this is too long after you posted to find any help or what you determined, but I think I may be in the same situation. My symptoms all point to a pituitary tumor and I am very scared. I’ve had Synarel in the early 90’s, Lupron, Progesterone and blood thinners to stay pregnant…a walking medical experiment due to endometriosis. I am having symptoms: headaches, dizzyness, vision changes, white flashes, no adrenaline, FSH is 180…YES, 180. Menopause set in and I started taking estrogen, but even that is not helping my lack of drive, though it has helped some symptoms. I am very suspicious of the Synarel, et al. Did you find any answers?

  12. KT Says:

    Hi im KT. I had my last lupron shot a year ago June. The Lupron was not so bad. I had hot flashes and night sweats but that was it. I have endometriosis, and the lupron helped me ovulate after two years not ovulating. My problem is that starting of September last year I started to gain weight. I have slowly gained 40 pounds since. I have been hardcore dieting for over a month with out loosing anything. I am excersizing and eating the right foods, and not starving myself. DId anyone else have problems after?

  13. bing constantino Says:

    Im on my 2 month injection of lupron.But still having menstruation.Any thoughts?

  14. Amy Says:

    I noticed no one’s answered your question & I don’t know. I suspect not many people check in here very often, but I know some of the women on the string about abdominal myomectomies have, so try asking the same question there:

  15. Debbie Says:

    Hi everyone , just found this brilliant website and thought i’d post a messgae to see if anyone can shed any light on my worries? i was on my 4th attempt of IVF back in july when i went for my 1st scan , my doctor diagnosed my really large fibroid ( 20 wks ) something like 20cm ! to be honest i wasnt shocked , i was more relieved really as i’d been to my own gp and A&E with pains im my stomach and a gut looking like i was ready to drop , both doctors told me if was muscle ( a 6 pack lol,) i could feel and not to worry. So I went away thiing docs know best !
    anyway to cut it short my fertility doctor took me straight of my IVF cycle and sent me for an MRI scan , i was back at the hospital last week and have just had my 1st injection to help shrink it ( i think i only have the one fibroid ) the thing is my doctor tells me i’ll be on the injections for 6 months? does it really take so long to shrink these fibroids? my fertility drugs i’ve just paid £800 for run out in oct 08 and i’m stressing that they’ll be out of date before i can use them. He’s told me my operation will be march 08 and not before .
    Im 37 and hoping once this thing is out my next bout of IVF will be successful, time will tell i suppose .
    has anyone else had these injections for 6 months ?
    thanks for a really informativeforum x

  16. jean Says:

    Hi What is the name of the injection you had. There is a site for lupron. lupron@yahoolcom

  17. Debbie Says:

    Hi Thanks for your reply , im taking decapeptyl 4.2mg , i had my 1st injection over 2 weeks ago and so far not many side effects . a couple of hot sweats in the 1st few days but other wise i seem to be fine , ( my hubby might not agree he might accuse me of having mood swings lol. )
    is anyone else on these injections ?

  18. Irina Says:

    I am going to get lupron shots and very nervous about side effect. Before get a surgery my doctor says that i need to try lupron. Please anyone let me know if i can try or forget about it?

  19. Lynn Says:

    I have taken lupron for 6 months and my periods are not stopping whatsoever. Does this mean something is really wrong with me? I told the GYN and he blew me off. I already ha surgery in May to remove my ovary and fallopian tube.

  20. renee Says:

    I just had my first injection of zoladex as a treatment regimen for IVF. I tried to use BCP for 2 months and I kept ovulating. So this time my doctor wanted me to use zoladex for suppression. Now, I have a question? It’s been 2 weeks since my injection and I have cramping and brownish discharge. Has anyone ever had this?
    I am not 100% clear on the pharmokinetics of this drug.
    I have headaches, I am lethargic and occassionally I get hot.

  21. renee Says:

    Well I had my U/s and my ovaries are completely suppressed. Zoladex does work, I guess the spotting and cramping was from the temporary surge in estrogen. Now, I am 3 weeks into the medication and the hot flashes have me running to the window and daydreaming about being in the middle of July. I now understand what my mother goes through with her hotflashes. All I can do is laugh!

  22. Jenny Says:

    Hello Renee,
    I was on Zoladex in 2006 after the operation to remove fibroids, to find also I had Endometriosis. I was free of pain for 7 months, the Zoladex was for 6 months. I was so happy happy and happy as I was free of pains, and I welcomed the hot flashes, sweats with smiles as it was 150% better than the pains. I didnt have other problems while in Zoladex. After that my gym recommended Danazol, which didnt work and I used for 11 months! I was ovulating while on Danazol, and my gyn was replaced with another one who seems not to be good in Endo. Now I am back in Zoladex, started to get sweats in my first injection last week but I hope I will be happy once again. What I dont understand is my Dr has put me 12 months in Zoladex 3.6! Which I find annoying according to some researches I read.
    Otherwise, I think Zoladex is better and it was for me, hope it will be this time as well.

  23. Tash Says:

    I’ve been taking Synarel for 7 months now. Very interesting to hear other peoples experiences of it as it doesn’t seem to be the drug of choice by many consultants.
    Its been tough as I’ve realised now I’m sensitive to hormones. So much crying in the first couple of months, night sweats and nightmares were a real problem for me. Its calmed down now so that I only have them every now and then. Quite low some of the time but I find now that things have settled that its just fatigue that is the main problem. I’m 27, fit and healthy but this stuff makes me need an hours kip in the afternoon or I’m just useless. I have to manage what I do as I can’t do the usual activities of a 27yr old at the moment. BUT having said all that, I think its worth it as symptoms are greatly improved. Just hope it stays that way after in 5 months when I come off it…..

  24. Juls Says:

    I am 45 yrs old and have had heavy menstrual bleeding 150ml+ per day for 2 days then bleeding for a total of up to 14 days. Have had 2 hysteroscopies first in 2000 where 2 small polyps were found D & C. Unfortunately had a small bacterial infection caught from hospital after this surgery which wasn’t treated for some months. Then still had symptoms off & on bleeding getting steadily worse with these more severe last 3 years. Another D & C hysteroscopy showed very thickened bac k wall of uterus. So now booked for Endometrial Ablation. Have been injected with Zoladex 3.6mg which should have worn off. It was injected after ovulation so went on to have normal (for me) heavy bleeding 2 weeks after the injection and am still bleeding after start of this period 2 1/2 weeks later. Have had hormonal type headaches as well but the worst is the veins in my legs & feet!! They have enlarged and luckily I am able to put my feet up, but am dismayed at what it has done and I am still 1 1/2 weeks away from my op!! It also has caused me to have weight gain!! I am not amused at all as the vein problems could become a problem!! Anyone else have this happen. I never would go on this again!!

  25. Lola Visnijic Says:

    Quick Question….
    I was on Zoladex for 6 months, 2 three monthly shots and a month later after the implant should have worn off, I am having the most horrific sweats………

    How long should I wait until I panic, that I have been forced into the Menpause, I am 26 so this would not be good.


  26. Felicia Says:

    I was on lupron depot 3.75 mg for 6 months. Experienced the hot flashes, night sweats, few headaches (borderline anemia), mood swings (not many). My objective is to become pregnant. My last injection was April 21, 2009, yet to have my period. My doctor informed me that if I do not have a period by June 19, 2009 he will induce it. I suffered from mild/moderate endo. Had an eptopic pregnancy in February 2007, followed up with my first lap in November 2008 and was diagnosed with endo. After completing the lupron, my doctor thought he was going to have to surgically remove the adhesions, but thanks to lupron, most of them were gone. All of my endo did not heal, but most of it did. My doctor says I have a 30-50% chance of getting pregnant. Not to mention my left tube doesn’t seem to be functioning properly (had eptopic in left tube); he mentioned if I don’t become pregnant soon, he will do surgery to get it to functioning properly. As for ovulation, if I am not ovulating on my own, he will give me clomid. My only problem now is the sleep meds doesn’t work any longer. I have not had ANY sleep in two day; on the other hand, I am trying to get off of them also. I have been feeling crampy like my period will come on soon, but nothing yet. I am really not worried because June 19, is around the corner and I know God did not bring us this far to leave us. We will have a successful pregnancy this year…may-be twins. Good luck for all of the new comers of lupron. Always remember the reason why you have decided to take lupron and the good will ALWAYS outweigh the bad…GOOD LUCK!!!

  27. Sylvia Says:

    Hated zolodex … Did not do what it meant to- fibroids barely shrank. I was miserable. Think it made my fibroids grow more.

  28. Kasia Says:

    I had my last lupron shot Feb. 24 2009. I got 2 different shots that lasted for 3 months each! It should be getting out of my system now. How long before I will have a menstral cycle again???

  29. Tell me about Lupron Synarel and Zoladex gonadotropin releasing | Menopause Relief Says:

    […] Tell me about Lupron Synarel and Zoladex gonadotropin releasing Posted by root 6 minutes ago ( Feb 21 2007 elevated levels of estrogen in the blood inhibit the secretion of gnrh lh this initially causes an increase in secretion of lh and fsh all there to induce temporary menopause so those symptoms are all the same comment on is anyone having probl Discuss  |  Bury |  News | Tell me about Lupron Synarel and Zoladex gonadotropin releasing […]

  30. Inez Says:

    I am on lupron depot 3.75 mg for 4 months June 19th Last Injection,has anyone taken it in the past?,if so how long did it take to leave your system. I had stage 2 endo ,did a lap then went on lupron

  31. wendy Says:

    FEMALE , i am taking zoladex 3.6 mg and the side effects are horrible, especially the pain in my fore head, is there anyone experiencing this, please let me know what you do

  32. Raya Says:

    Hi I have many fibroids and two main doctors.
    One doctor in the caribbean and one in the states. My doctor in the states recommended Lupron and my doctor in the caribbean can only get his hands on Zoladex.

    The add back drug, my doctor in the states recommended is Notherindrone Acetate 5mg, while my doctor in the caribbean can only recommend the pill as an add back.

    I knew about the drugs and was against it for so long. Now my fibroids have grown to 12.5cm and I have wasted a whole year.

    I guess I just have to take the zoladex or fly to the states to get the Lupron.
    Or take the Zoladex to save time and money.

    So many horry stories.

    I have finally decided to take the Lupron and no

  33. KeyLimePie Says:

    DON’T take LUPRON !!! I thought it would probably be OK to take ONE 3.75mg shot. My doctor pushed it. I have never recovered! I look and feel pregnant nine months later with a bloated distended abdomen. I’m only 92 pounds! So much discomfort. Doctors aren’t helping me. I was perfectly healthy and happy before I took this drug. This drug is much more dangerous than your surgery. Please take what people are writing seriously! There’s no turning back! 23% report permanent side effects.

  34. Jess Says:

    Hi, I have just had my 2nd Laparoscopy (my first was 2009) I have severe endo which is on my womb, fallopian tubes, ovaries and bladder. Both times the Con said they couldn’t remove the endo on my bladder because the hystoscopy doesn’t allow this. I have therefore been on Zoladex twice, the first time for 4 months and now I am starting a 6 month treatment. Today I have started cramping and bleeding heavily (and I am not on my period). I rang my cons and was told that this can be a side effect of Zoladex. I never had this side effect before and am concerned. I am also going to have a 3 month injection next time and then a 3 month one agian as my GP doesn’t think there is any harm in this additional month. My problem is that once the Zoladex wears off I will be back at sqaure one and the cramping will start again. The main side effect I remember is the hot flushes, but they are a million times better than the severe cramping I was getting. Hope this helps.

  35. Amado Levans Says:

    A distended stomach normally designates an increase in the girth of the stomach. It normally results because of an escalation in pressure intra-abdominal which drives the wall of the abdomen out as well as being the reason why the stomach distends..

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  36. want to be a momma Says:

    I recently had Laparoscopy for level 3 endo. My husband and I have been trying to get pregnant for 2 years and have had 1 miscarriage. My gyn is recommend Lupron, however, I am concerned about the research I have reviewed regarding side affects. I was not aware of synarel or any other medication to do the same “menopause” like state. Any recommendation between the two medications would be greatly appreciated. I can not find any research for pregnancy rates after treatment for either medication. Would anyone have any information regarding this treatment approach? Thank You

  37. Jenny Says:

    I have had two shots of Zoladex and a recent Laparoscopy. The hot flushes are unbearable and I have severe joint pain. I was wondering how long before the Zoladex leaves my system.

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