What Is The Best SERM
- Thread starter xtreme1
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GuitarHero
Member
READ THIS: No Excuses & No ***** ***: A Stupid People's Guide to PCT
Tamoxifen and Clomid are the old stand-by SERMs, but they're also known to be more hepatoxic than something like Toremifene. I've used Tamoxifen and it worked well, but I went with Toremifene for my next cycle because of the toxicity issues.
Tor is more expensive though...
Tamoxifen and Clomid are the old stand-by SERMs, but they're also known to be more hepatoxic than something like Toremifene. I've used Tamoxifen and it worked well, but I went with Toremifene for my next cycle because of the toxicity issues.
Tor is more expensive though...
LakeMountD
Doctor Science
Actually in many cases the difference in price between toremifene and tamoxifen is only like $10-$20. With toremifene helping lipid values as much as it does I think it is worth it.
But considering you wrote "PST" I think you need to do A LOT more research before getting yourself into anything. Read the thread posted above thoroughly.
But considering you wrote "PST" I think you need to do A LOT more research before getting yourself into anything. Read the thread posted above thoroughly.
dmangiarelli
Board Sponsor
I'd say it really depends on the compound you are cycling.
Clomid>>Toremifene>>Nolvadex
Clomid>>Toremifene>>Nolvadex
xtreme1
New member
H-Drol/S-Drol clone.
Australian made
Well-known member
Dont stack those together on your first cycle. In fact never stack those two together. Run the H-drol first and save the s-drol for another time................but i dont think your prepared for a steroid cycle anyway.
xtreme1
New member
Check out my posts on other threads. I did my homework and ran my cycle safe. Just could not get a SERM. So I got some Novedex and ordered some Cycle Support.
Mass_69
Well-known member
My guess would be PST means "post steroid therapy"? Definitely read through the post above, and do some more searches. There's a lot of info on this subject on this board. A SERM is heavily advised for these 2 products.
BTW, many dispute the claim of Clomiphene & Tamoxifen's hepatoxitity, mostly that it's overstated. On the other hand, there are many better (more efficient) options for PCT than Tamox.
AlexParty
Yari Ka Daw!
Well a compound less potent. I used Phera Plex and didn't use a serm after and was perfectly fine, as a matter of fact most people who used phera didn't serm. If you did your just being safe and that's perfectly fine but if I was doing something hard I would use a serm.
Actually I'm doing a havoc cycle and I was told to use a serm so I have one on hand in case but I think it might be over kill.
Ziquor
Well-known member
This's is one of those ?'s like what's the best car. None - they all have advantages & disadvantages. However if I had to base upon which had the most benefits I'd rate like this with#1 and #2 being close:
(1) Toremifene
(2) Tamoxifen
(3) Clomid
And novedex isn't a serm nor are any OTC supps.
(1) Toremifene
(2) Tamoxifen
(3) Clomid
And novedex isn't a serm nor are any OTC supps.
Ziquor
Well-known member
I'd personally never take Phera & not serm. The point of serming is getting HPTA - natural test levels back to normal as quick as possible. If you don't there's always a possibility that your natural test could be lower than it should for life being suppressed for too long. I have a close friend who didn't serm after an oral cycle & his natty test levels have been extremely low since. He can't have sex anymore & this was over a year ago.
AlexParty
Yari Ka Daw!
Holy **** that sucks. I ran my cycle low at 20 mg a day for 4 weeks which is probably why I was safe and ya maybe I should have used a serm but everyone logging on this site didn't use one and said it wasn't necessary. How old was he?
AlexParty
Yari Ka Daw!
Novedex XT isn't Nolvadex, they sound similar but aren't the same. To be honest I don't know if you should use a serm for your H-Drol cycle but with all this serm talk now it's probably best to be safe and run it afterwards or hold it in case.
AlexParty
Yari Ka Daw!
What's to be confused about? Ask and we'll try and make it more clear.
Mass_69
Well-known member
I tend to stick with the safer route. In my anecdotal experience, my AI-only PCTs (before really knowing what I do now) didn't tend to fare too well, and I've always felt better and more "recovered" with SERMs. Also, don't forget the lipid recovery you get with SERMs. AIs tend to actually lower them.
LakeMountD
Doctor Science
As mass is saying above just go with a SERM. To make things easier I am going to say go with toremifene. Despite the degree, it is less toxic, recovers lipid (cholesterol) levels greatly, and tends to bring libido back faster with much lower side effects than the other two.
Tamoxifen (Nolvadex) doesn't really have bad sides but why get something that doesn't recover the lipids as well and is more toxic? Clomid, though many swear by it, has a hell of a lot more side effects and is definitely a more antiquated drug than Toremifene. Heart disease is the number one killer and it is mainly caused by atherosclerosis which is the buildup of plaque on the arterial walls. High LDL mixed with low HDL is a recipe for this. You want to cater to keeping your lipid levels as good as possible. Spend the extra $20 and get the toremifene
.AlexParty
Yari Ka Daw!
One will do, you don't need both and according to everyone else use torm. I would personally use nolva since it's solid but everyone likes torm and I might even give it a shot one time.
TheNoid
Registered User
Most of what has been spewed in this thread is complete bro-telligence based on only anecdotal evidence. If you really have concerns about restoring HPTA with the help of a serm in PCT then use clomid/tamox. These are the only 2 serms actually proven in a study to restore HPTA post exogeneous steroid cycle (and even this study was shaky if I recall).
If you looking for a libido boost and help in the lipid department (likely after SD use), then go with torem. But at this point torem is only popular based on anecdotal evidence and some hypothesis based on womens breast cancer studies.
If you looking for a libido boost and help in the lipid department (likely after SD use), then go with torem. But at this point torem is only popular based on anecdotal evidence and some hypothesis based on womens breast cancer studies.
LakeMountD
Doctor Science
Bro-telligence? Not sure which post you are referring to but toremifene's efficacy is anything but unproven.
TheNoid
Registered User
In terms of what? I wasnt referring specifically to your posts and based on user reports/bloodwork I'm sure torem is great, but as far as actually restoring HPTA its basically speculation until I see some evidence in a controlled study.
poopypants
Banned
Umm noid Im sorry but you are completely WRONG.
Torem has many studies done on it and MANY of those studies were ones done with it going head to head with Nolva and showing how much better it was. Maybe before making your second post on these boards youd bother researching on this very site regarding the subject and see all the MULTPLE studies our "brotelligence" is based on.
NOW....
Xtreme, Id go with torem over the others any day of the week, STUDIES aside I have used both nolva and torem for similar cycles and recovered and felt MUCH better using torem. Yes, Nolva does work and get the job done but torem does so much faster and better with less sides and toxicity. And if you want to talk about making PCT a B!TCH or turning you into one then just try using clomid instead, the stuff is insanely great for HTPA restoration but has extreme mood related sides and doesnt effect the estrogen side of things nearly as well as the others.
TheNoid
Registered User
What exactly in my post is wrong?
You are right there....but are they relevant to PCT? If you have some by all means shoot.
Good save, maybe you should go outside the world of AM once an d realize this is by far the most SERM happy recommending board/information source out there. Am I saying that is wrong? No, but I expected nothing less than a response such as this...
Here is an abstract that partially supports your opinion, but it relates to low sperm count and never states improvements on LH:
But do you recommend 60mg's to users for 3 months? I dont see jack about sides mentioned either. User weight, drugs, and cycle length should all be reviewed before recommending a blind dosage. None of which is mentioned....Lake perhaps you have full access?
Here is an actual study dont with clomid/nolva:
Invalid Link Removed
The OP asked "which is the best SERM" frankly there is no answer to that imho. My opinion is useless b/c I only have 4 posts or whatever though.... :fool2:
LakeMountD
Doctor Science
I'll have access tomorrow at the science library. Who said increases in LH were the only factor involved in increasing HPTA output? There are so many things that go into getting the system back on track you can't single it out to one particular thing. I would have to dig again because I haven't looked into this subject in quite some time but there are studies that I have read that explains the way in which SERM's can bring this system back to where it was pre cycle faster. Some work at the pituitary level, some at the gonadal level, and some work at a combination of both.
Don't get me wrong I am big into the studies. I am a doctoral student and I rely heavily on them, but even with the limited information available I much rather be safe than sorry. There is also something to be said about user reports. Whether there is science backing something or not you can't go against user reports. There are so many lurking variables that sometimes you just can't single them out. Heck, pre 1990's no one understood the myostatin gene and couldn't figure out why some, no matter what, would gain muscle so easily. They could have contributed it to something they were exposed to when they were young or something else.
TheNoid
Registered User
I agree with your post completely (particularly points in bold). In regards to LH being the only factor, I dont think I stated that, but it is nonetheless one of the many factors.
Its pretty much an endless argument, only wanted to point out another perspective. Reps
LakeMountD
Doctor Science
I am glad you did. A forum isn't a forum unless you have someone debating the information with you. At least you did your own homework and questioned things. That is what science is about. Science is not about testing yourself right. It is about trying to test yourself wrong. Create a hypothesis and set out to prove it wrong.
Reps back for not being a lemming
.pudzian2
Banned
I have read several studies suggesting that Torem doesnt increase LH output contrary to other serms (clomid comes to mind) but torem in other regards ACTS like clomid (minus the sides) while being a structural relative of tamox....the more I read into it all the more confusing it gets. Like LMD said, theres just too much more to it than simple LH boosting. That can be done WITHOUT a serm... I have found raloxifene to work VERY well for me. after a 19 week injectable. (well first 3 weeks PCT torem, then switched to ralox but as soon as I did I felt 2000 times better, libido and all). This doesnt really prove anything because it could have been an accumulated affect of torem, or it could have been from the ralox.... who knows.
LakeMountD
Doctor Science
Exactly. Lurking variables play a large part in every day life and they can't be overlooked. Take everything you read with a grain of salt. This is one of the reasons why I stress the lipid improving effects of toremifene over everything else.
pudzian2
Banned
I agree. I am going to try a torem/ralox combo for my next PCT and see how that works....if nothing else torem will benefit lipids and exert selective estrogen modulating benefits, and ralox will do it's part. then again.... combining the two may cause each to have totally different actions in the body... I will see. I am leaning towards using both together for the first week only and then using one for the rest.
then again I am designing my futurecycles to require little, if any PCT (in the form of SERM/AI use)
poopypants
Banned
Im sorry noid my post was made in regards to you throwing out the brotelligence quip.
The posts made by the fellows here are made on multiple variables not JUST htpa restart, he asked for the best SERM not which had the most research regarding HTPA restart. We gave him valuable info based on studies done on more then JUST htpa namely improving the lipids and the lack of toxicity.
He didnt ask for doses either and I didnt give him a specific blind dosing regimin, since as you said there are multiple factors that should be taken into account.
I would love to say there was as much applicable studies out there regarding Toremifene as there are for a clom/nolva combo but bottom line is there is not. Ther is however a multitude of other studies done regarding the safety of torem over tamox while providing better results in the studies varied applications. Not to mention a lot of user feedback and bloodwork done showing the restoration of values to norm or better then norm ranges using toremifene, these cannot just be ignored and considered useless.
I dont think you can come in here and make the accusation of all the advice being pure "brotelligence" without reading te many similar threads that have been discussed as of late and most certainly the posting history of those giving the advice. If you had done so before your 2 posts you would have realized your quip was unfounded and is totally deserving of my response.
I too applaude your questioning and want for more info but the fact is it could be done with more tact and less insults.
LakeMountD
Doctor Science
Here ya go....
The beneficial effects of toremifene administration on the hypothalamic-pituitary-testicular axis and sperm parameters in men with idiopathic oligozoospermia
Dimitrios Farmakiotis M.D.a, Christos Farmakis M.D.a, David Rousso M.D.a, Anargyros Kourtis M.D.Corresponding Author Contact Information, a, E-mail The Corresponding Author, Ilias Katsikis M.D.a and Dimitrios Panidis M.D., Ph.D.a
aDivision of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Received 8 August 2006; revised 22 December 2006; accepted 22 December 2006. Available online 6 April 2007.
Objective
To evaluate whether toremifene, a selective estrogen receptor modulator (SERM), has a beneficiary effect on all three main sperm parameters.
Design
Prospective interventional clinical study.
Setting
University hospital.
Patient(s)
One-hundred subfertile men with idiopathic oligozospermia.
Intervention(s)
Toremifene (60 mg daily) was administered to all men for 3 months. At baseline and at the end of each month, serum concentrations of follicle-stimulating hormone (FSH), testosterone, inhibin B, and sex hormone–binding globulin (SHBG) were measured. At baseline and at the end, semen analysis was performed and sperm concentration, spermatozoal motility and normal sperm forms were determined.
Main Outcome Measure(s)
Gonadotropin, testosterone, inhibin-B levels, total sperm count, sperm morphology and motility.
Result(s)
Toremifene administration resulted in a significant increase in FSH, testosterone, SHBG, and inhibin B levels, as well as in sperm concentration, percentage motility and normal sperm forms. Twenty-two men's partners achieved pregnancy within 2 months of the end of treatment. At the end of the third month, serum FSH levels were significantly higher in the men whose partners did not achieve pregnancy, and total sperm count and normal sperm forms were significantly lower compared with the group of men whose partners achieved pregnancy.
Conclusion(s)
Toremifene administration for a period of 3 months in men with idiopathic oligozoospermia is associated with significant improvements of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. The above findings are also indicative of a better testicular exocrine (improved sperm parameters) response to treatment in men whose partners achieved pregnancy compared with those who did not. Further randomized, placebo-controlled trials should be conducted to determine whether this particular selective estrogen receptor modulator can be useful as an initial approach in men with oligozoospermia.
Key Words: Toremifene; oligozoospermia; male infertility; SERM
Article Outline
Materials and methods
Patients
Study Protocol
Hormonal Measurements
Semen Analysis
Statistical Analysis
Results
Effect of Treatment
Differences between Men Whose Partners Achieved Pregnancy and Those Whose Partners Did Not
Discussion
References
A selective estrogen receptor modulator (SERM) is a compound that can act as an estrogen agonist or antagonist, depending on the specific target tissue (1). At present, four SERMs are approved for clinical use: clomiphene, raloxifene, tamoxifen, and toremifene. Three of these compounds belong to the triphenylethylene family: clomifene, tamoxifen, and toremifene. Raloxifene belongs to the benzothiophene family (2).
Most of the unique pharmacology of SERMs can be explained by three interactive mechanisms. The first is differential estrogen-receptor expression in a given target tissue. The second consists of the differential estrogen-receptor conformation on ligand binding. The third is the differential expression and binding to the estrogen receptor of coregulator proteins (3).
In women, at least three SERMs have been shown to increase circulating levels of gonadotropin. The exact mechanism for this effect is based on the estrogen antagonistic properties of SERMs at the hypothalamic and pituitary level (4). In addition, SERMs have been shown to increase sex hormone–binding globulin (SHBG) levels, which can be attributed to the estrogen agonist activity of SERMs in the liver (2) and (3).
There have been relatively few studies of SERMs in males. Clomiphene citrate and tamoxifen have been proposed for the management of male factor infertility (1). Tamoxifen citrate was introduced 30 years ago as an empiric treatment for idiopathic oligozoospermia because of its stimulatory action on gonadotropin secretion and its postulated direct effects on Leydig cell function and 5α-dihydrotestosterone production in seminiferous tubules and epididymis (5). The main effect of tamoxifen on spermatogenesis is stimulatory, resulting in a twofold increase in spermatozoa concentration. Such an increase in spermatozoa concentration may be important because a change of this magnitude at the low range of spermatozoa concentrations found in oligozoospermic men has been associated with disproportionately higher fecundity. However, this particular SERM has not been shown to induce any marked changes in motility and morphology (6) and (7).
The effect of treatment with tamoxifen citrate on cumulative achievement of pregnancy over a long period of time is similar to that of assisted reproductive techniques (ART) (8) and (9). On the basis of these results (6), (10) and (11), tamoxifen citrate was proposed by a World Health Organization working committee as the first line of treatment for idiopathic oligozoospermia (12).
Because tamoxifen increases spermatozoa concentration but has no marked effect on spermatozoa motility and morphology, this study was designed to evaluate whether another SERM, toremifene, has a beneficiary effect on all three main semen parameters. To the best of our knowledge, no previous data have been reported concerning the effect of this specific SERM on the hypothalamic-pituitary-testicular axis and semen parameters in men with idiopathic abnormalities in one or more of the three main semen parameters.
Materials and methods
Patients
One hundred subfertile men with idiopathic oligozoospermia, mean (± SEM) age 20 to 47 years (33.53 ± 0.5 years), were consecutively recruited from the fertility center of our department. All of the men were characterized as subfertile because they had been unsuccessful in achieving pregnancy with their partners for 12 months, although their partners did not show any of the known causes of female subfertility.
Idiopathic oligozoospermia was defined as quantitative and/or qualitative aberrations of sperm variables according to World Health Organization criteria (12). Men with known or demonstrable causes of oligozoospermia (varicocele, infections, autoimmunity, stress, chromosomal abnormalities, environmental factors, or epididymitis) were excluded.
Careful clinical examination showed that all of the men had complete development of the secondary sex characteristics, with a mean (± SEM) right testicular volume of 18.45 ± 0.39 cm3 and mean (± SEM) left testicular volume 17.80 ± 0.41 cm3 (mean testicular volume 18.14 ± 0.39 cm3). Total testicular volume was assessed by comparison with a standard value on orchidometry. None of the men had received any medication during the 6-month period preceding the study.
Study Protocol
All of the men received toremifene as monotherapy at a dose of 60 mg daily for a period of 3 months. At baseline, and at the end of the first, second, and third month of treatment, blood samples were collected at 9 am after an overnight fast.
All samples were centrifuged immediately, and serum was stored at −70°C until assayed for FSH, testosterone, inhibin B, and SHBG. Sperm was examined at baseline and at the end of the third month of treatment. All participants were properly informed about the purpose of the study and gave informed written consent. The study was approved by the ethics committee of the hospital.
Hormonal Measurements
We measured FSH (IU/L) using the FSH IRMA kits from Biosource Technologies (Vacaville, CA). Total testosterone (ng/dL) was measured by enzyme-linked immunosorbent assay (ELISA; testosterone enzyme immunoassay test kit, LI7603; Linear Chemicals). The serum levels of SHBG (nmol/L) were measured by ELISA (SHBG ELISA, MX 520 11; IBL, Hamburg, Germany). Inhibin B levels were measured using ELISA kits from Oxford Bio Innovation DSL Ltd (Upper Heyford, Bicester, Oxfordshire, United Kingdom).
Semen Analysis
Semen was collected by masturbation into sterilized glass containers after a 3- to 6-day abstinence. After evaluation of liquefaction and measurement of viscosity and volume, motility was measured, at room temperature (22° to 25°C), 1 hour after ejaculation, as previously described elsewhere (12), (13), (14) and (15).
Sperm morphology was evaluated from Papanicolaou-stained smears, and the classification of abnormal sperm forms was made according to the guidelines of the WHO (12). One hundred spermatozoa were studied from each semen specimen, and the same individual (D.P.) evaluated all smears. The percentage of motile spermatozoa was measured by the subjective method at room temperature (22° to 25°C), and sperm concentration was determined in an undiluted semen specimen with the use of Makler's Counting Chamber (16) and (17).
Statistical Analysis
Statistical analysis was performed with SPSS statistical software, v. 13.0 (SPSS Inc, Chicago, IL). Two-tailed statistical significance was set at 5%. Categorical parameters (smoking status) were compared with Fischer's exact test. The normality of distribution was assessed with the Kolmogorov-Smirnov test (K-S) test. Values that did not fit the normal distribution were log-transformed.
Mean was compared at baseline with Student's t-test and during treatment with general linear model–based two-way repeated measures of analysis of variance (ANOVA); time (treatment) was set as the within-groups factor and achievement of pregnancy as the between-subjects factor. Within-groups post hoc analysis was performed after Bonferroni adjustment for multiple comparisons. Between groups post hoc analysis was based on model parameter estimates.
For those parameters where statistically significant or borderline differences or interactions between the men whose partners achieved pregnancy and those who failed were observed, binary logistic regression analysis was also performed to assess prognostic value.
Results
The basal epidemiologic and anthropometric features of the men studied are presented in Table 1. Twenty-two men had partners who achieved pregnancy within 2 months from the end of treatment (22%; 95% CI, 15.0–31.1%). The hormonal features before and during treatment with toremifene of the men whose partners eventually achieved pregnancy (group 1) and those whose partners did not (group 2) are summarized in Table 2, and their semen parameters are presented in Table 3. Men whose partners achieved pregnancy did not differ significantly in epidemiologic and somatotopic features from the other group (see Table 1).
Table 1.
Epidemiologic and anthropometric features of the men in couples who eventually achieved pregnancy (group 1) and those who did not (group 2).
Group 1 (n = 22) Group 2 (n = 78) P
Age (years) 32.86 ± 1.14 33.72 ± 0.57 .487
Age of spouse (years) 30.23 ± 0.98 29.77 ± 0.58 .707
Right testicle volume (mL) 18.86 ± 0.79 18.33 ± 0.46 .584
Left testicle volume (mL) 18.91 ± 0.83 17.49 ± 0.47 .157
Mean testicle volume (mL) 18.89 ± 0.73 17.94 ± 0.45 .316
Body mass index (kg/m2) 28.23 ± 0.83 26.85 ± 0.41 .125
Smoking status (smokers) 10/22 37/78 .532
Note: Baseline is mean ± SEM. Statistical significance determined by Student's t-test after log-transformation, Fischer's exact test for smoking status.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
Table 2.
Basic hormonal features before and during treatment with toremifene of the men in couples who eventually achieved pregnancy (group 1) and those who did not (group 2).
FSH (mIU/mL) T (mmol/L) SHBG (nmol/L) FAI INH (pg/mL)
Group 1 (n = 22)
Baseline 4.99 ± 0.54 5.10 ± 0.33 21.82 ± 1.47 96.55 ± 13.28 148.54 ± 15.62
1 m 8.05 ± 0.78 7.18 ± 0.45 26.46 ± 2.20 116.81 ± 18.05 158.98 ± 16.46
2 m 8.36 ± 0.91 7.28 ± 0.72 25.25 ± 1.42 109.00 ± 12.05 163.57 ± 17.15
3 m 9.20 ± 0.91 6.91 ± 0.54 24.89 ± 1.62 109.47 ± 9.79 160.02 ± 20.61
Group 2 (n = 78)
Baseline 6.78 ± 0.61 4.85 ± 0.86 17.65 ± 0.65 96.55 ± 13.27 146.28 ± 8.64
1 m 9.51 ± 0.77 6.87 ± 0.23 23.16 ± 0.96 116.81 ± 18.05 152.41 ± 8.86
2 m 10.22 ± 0.74 6.91 ± 0.26 21.73 ± 0.84 109.00 ± 12.05 156.33 ± 9.48
3 m 10.73 ± 0.74 7.19 ± 0.24 23.60 ± 0.77 109.47 ± 9.79 155.65 ± 8.21
Group
F 3.432 .086 3.519 0.210 .078
P .067 .770 0.064 0.648 .781
Time
F 87.480 32.814 12.793 3.982 3.385
P <.001 <.001 <0.001 0.013 .025
Group × Time
F .518 .848 1.657 0.474 .143
P .670 .468 0.190 0.665 .909
Note: Mean ± SEM. Statistical significance by two-way repeated measures analysis of variance after log-transformation. FAI, free androgen index; FSH, follicle-stimulating hormone; INH, inhibin B; T, testosterone; SHBG, sex hormone–binding globulin.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
Table 3.
Semen parameters before and during treatment with toremifene of the men in couples who eventually achieved pregnancy (group 1) and those who did not (group 2).
Sperm concentration (× 106/mL) Total sperm count (× 106) Spermatozoal motility (%) Normal sperm forms (%)
Group 1 (n = 22)
Baseline 29.48 ± 4.04 109.62 ± 16.21 39.97 ± 3.43 23.86 ± 3.32
3 m 45.57 ± 4.13 171,58 ± 22.88 49.76 ± 1.91 37.23 ± 3.02
Group 2 (n = 78)
Baseline 26.86 ± 1.79 91.71 ± 7.19 35.94 ± 1.62 21.67 ± 1.29
3 m 38.19 ± 2.46 121.71 ± 8.89 45.02 ± 1.62 29.92 ± 1.57
Group
F 1.349 4.223 2.209 2.726
P .248 .043 .140 .102
Time
F 70.287 30.417 32.612 62.905
P <.001 <.001 <.001 <.001
Group ×Time
F 2.123 3.674 .046 3.510
P .148 .058 .831 .064
Note: Mean ± SEM. Statistical significance by two-way repeated measures analysis of variance after log-transformation.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
Effect of Treatment
During treatment with toremifene, a significant increase in circulating levels of FSH (Fig. 1), testosterone, and inhibin B levels was observed (P<.001 for FSH, and T, P<.05 for inhibin-B; Table 2). SHBG levels (P<.001) and free androgen index (FAI) values (P<.05) (Fig. 2) levels was observed. The number of spermatozoa per mL, as well as per ejaculation, and the percentage of spermatozoa with normal motility and morphology were also significantly increased at 3 months (P<.001; Table 3).
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Figure 1. Follicle-stimulating hormone levels (mean ± SEM) of the men whose partners eventually achieved pregnancy and those whose partners did not, before and during treatment with toremifene. *P<.05 versus previous value, †P <.05 between the men whose partners became pregnant and those whose partners did not.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
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Figure 2. Inhibin B (INH) levels (mean ± SEM) of the men whose partners eventually achieved pregnancy and those whose partners did not, before and during treatment with toremifene.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
The increase in FSH levels was basically observed during the first (P<.001) and second (P<.05) months of treatment, whereas the change during the last month was not significant. Testosterone (T) and SHBG levels (P<.001), as well as FAI values (P<.05), were significantly increased only during the first month (P<.001), while the increase in SHBG levels was significant during both the first and second month (P<.001); no significant change in T levels, SHBG concentration, or FAI was observed during the second and third month of treatment.
Differences between Men Whose Partners Achieved Pregnancy and Those Whose Partners Did Not
Overall, FSH levels were borderline higher in those men whose partners did not achieve pregnancy compared with those whose partners did (P=.067; see Table 2, Fig. 1). The difference between the two groups was statistically significant at the end of treatment (P<.05; see Fig. 1). Likewise, the total number of spermatozoa per ejaculation was, overall, statistically significantly higher in men whose partners achieved pregnancy (P<.05; see Table 2, Fig. 3). This difference was, again, statistically significant at 3 months (P<.05) but not at baseline (see Fig. 3).
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Figure 3. Total number of spermatozoa (SZ) per ejaculation (mean ± SEM) of the men whose partners eventually achieved pregnancy and those whose partners did not, before and after 3-month-treatment with toremifene. *P <.05 versus previous value. †P <.05 between the men whose partners became pregnant and those whose partners did not.
Farmakiotis. Toremifene in male infertility. Fertil Steril 2007.
A borderline interaction between time and treatment outcome (pregnancy or no pregnancy) was observed with respect to the total number of spermatozoa per ejaculation (P=.058; see Table 2, Fig. 3) and the percentage of spermatozoa with normal morphology (P=.064; see Table 2). Men whose partners achieved pregnancy had a statistically significantly higher percentage of spermatozoa with normal morphology at the end of treatment (P<.05).
In univariate logistic regression analysis, FSH levels (B = −1.894 ± 0.959), sperm count per ejaculation (B = 0.006 ± 0.003), and the percentage of spermatozoa with normal morphology (B = 0.04 ± 0.02) after treatment had a statistically significant prognostic value for the achievement of pregnancy (P<.05). In multivariate logistic regression, FSH levels at 3 months were the most statistically significant independent parameter of the three (B = −1.73 ± 1.02, P=.089).
LakeMountD
Doctor Science
Discussion
Tamoxifen citrate, a selective estrogen receptor modulator (SERM), has been proposed as an empiric treatment for idiopathic oligozoospermia because of its stimulatory action on gonadotropin secretion and its postulated direct effects on Leydig cell function and 5α-dihydrotestosterone production in seminiferous tubules and epididymis (5), (6), (10), (11) and (12). Based on the above evidence, the present study was designed to investigate whether toremifene, another compound from the same category (13), has a beneficiary effect on the main semen parameters as well.
In the present study, a statistically significant increase in serum FSH was observed after administration of toremifene at a dose of 60 mg daily. This increase was more marked at the end of the first month of treatment; FSH levels were also statistically significantly increased after one additional month of treatment, reaching a plateau after the end of the second month with no statistically significant increase during the last month of toremifene administration (see Table 2, Fig. 1). This increase should be attributed to the well-known anti-estrogenic properties of SERMs in general (3) and toremifene in specific (18) and (19). The stimulatory effect of SERMs on hypophyseal gonadotropin secretion has been proposed as a possible mechanism for its beneficial effect on semen quality (5).
Toremifene administration also induced a statistically significant increase in total testosterone levels, which was again significant only during the first month of treatment, reaching a plateau afterward (see Table 2). The increased gonadotropin secretion could be the reason for this observed increase in total testosterone levels (1) and (3). However, it should be noted that SERMs have also been reported to have direct stimulating effects on Leydig cell function (20) and 5α-dihydrotestosterone production in seminiferous tubules and epididymis (5) and (21).
Despite the increase in testosterone levels, which would be expected to suppress SHBG production by the liver (22), the levels of this globulin were statistically significantly increased during the first and the second months of toremifene administration (see Table 2). These results are indicative of the estrogenic activity of toremifene at the liver, which is consistent with previous reports on SERM properties (23).
An interesting finding of this study, which, to the best of our knowledge, has not been previously reported, was the statistically significant increase in circulating inhibin B after toremifene administration (see Table 2, Fig. 2). Inhibin production by the testes is stimulated by FSH; moreover, inhibin secretion has been proposed as a reliable index of Sertoli cell function. Therefore, the increase of inhibin levels observed in the present study could be attributed to both increased FSH secretion (see Table 2, Fig. 1) and the potential beneficiary effect of SERMs on testicular function (5), (20) and (21).
Toremifene administration for a period of 3 months resulted in a statistically significant improvement of all three main semen parameters, namely, sperm count (see Table 3, Fig. 3), motility, and morphology (see Table 3). It should be noted that, although tamoxifen has also been shown to induce a statistically significant increase in spermatozoa count, this particular SERM has not been shown to induce any marked changes in motility and morphology (6) and (7).
The partners of 22 men achieved pregnancy within 2 months from the end of treatment. At baseline, these men presented with lower serum FSH levels compared with those whose partners did not achieve pregnancy but not statistically significantly so. Although treatment with toremifene induced a statistically significant increase in FSH levels in both groups, FSH levels were statistically significantly lower (P<.05) in men whose partners achieved pregnancy at the end of the third month of treatment (see Fig. 1). We postulate that lower FSH levels in the men whose partners achieved pregnancy are due to a more functional negative feedback from the testes, thus reflecting better testicular response to treatment. This trend was also apparent in the higher levels of inhibin observed in the group of men whose partners eventually became pregnancy, although a level of statistical significance was not reached.
At baseline, no statistically significant differences in the three main semen parameters of sperm count, motility, and morphology were observed between men whose partners achieved pregnancy and those whose partners did not, although there was a trend for increased values in the former group. Notably, total sperm count as well as spermatozoa morphology was improved with toremifene administration; this change was more marked in the group of men whose partners achieved pregnancy (see Table 3, Fig. 3). Moreover, total sperm count and spermatozoa morphology at the end of treatment had statistically significant prognostic value for the achievement of pregnancy within the subsequent 2 months. This finding is again consistent with better testicular functional response in the subgroup of men whose partners achieved pregnancy.
Conclusively, the present study shows that toremifene administration for a period of 3 months in men with idiopathic oligozoospermia results in statistically significant improvements in all three main semen parameters of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. It is possible, therefore, that this particular SERM could be useful as an initial approach in the treatment of subfertile men with idiopathic oligozoospermia. Nevertheless, the precise standards of treatment need to be further investigated by randomized, placebo-controlled trials.
Tamoxifen citrate, a selective estrogen receptor modulator (SERM), has been proposed as an empiric treatment for idiopathic oligozoospermia because of its stimulatory action on gonadotropin secretion and its postulated direct effects on Leydig cell function and 5α-dihydrotestosterone production in seminiferous tubules and epididymis (5), (6), (10), (11) and (12). Based on the above evidence, the present study was designed to investigate whether toremifene, another compound from the same category (13), has a beneficiary effect on the main semen parameters as well.
In the present study, a statistically significant increase in serum FSH was observed after administration of toremifene at a dose of 60 mg daily. This increase was more marked at the end of the first month of treatment; FSH levels were also statistically significantly increased after one additional month of treatment, reaching a plateau after the end of the second month with no statistically significant increase during the last month of toremifene administration (see Table 2, Fig. 1). This increase should be attributed to the well-known anti-estrogenic properties of SERMs in general (3) and toremifene in specific (18) and (19). The stimulatory effect of SERMs on hypophyseal gonadotropin secretion has been proposed as a possible mechanism for its beneficial effect on semen quality (5).
Toremifene administration also induced a statistically significant increase in total testosterone levels, which was again significant only during the first month of treatment, reaching a plateau afterward (see Table 2). The increased gonadotropin secretion could be the reason for this observed increase in total testosterone levels (1) and (3). However, it should be noted that SERMs have also been reported to have direct stimulating effects on Leydig cell function (20) and 5α-dihydrotestosterone production in seminiferous tubules and epididymis (5) and (21).
Despite the increase in testosterone levels, which would be expected to suppress SHBG production by the liver (22), the levels of this globulin were statistically significantly increased during the first and the second months of toremifene administration (see Table 2). These results are indicative of the estrogenic activity of toremifene at the liver, which is consistent with previous reports on SERM properties (23).
An interesting finding of this study, which, to the best of our knowledge, has not been previously reported, was the statistically significant increase in circulating inhibin B after toremifene administration (see Table 2, Fig. 2). Inhibin production by the testes is stimulated by FSH; moreover, inhibin secretion has been proposed as a reliable index of Sertoli cell function. Therefore, the increase of inhibin levels observed in the present study could be attributed to both increased FSH secretion (see Table 2, Fig. 1) and the potential beneficiary effect of SERMs on testicular function (5), (20) and (21).
Toremifene administration for a period of 3 months resulted in a statistically significant improvement of all three main semen parameters, namely, sperm count (see Table 3, Fig. 3), motility, and morphology (see Table 3). It should be noted that, although tamoxifen has also been shown to induce a statistically significant increase in spermatozoa count, this particular SERM has not been shown to induce any marked changes in motility and morphology (6) and (7).
The partners of 22 men achieved pregnancy within 2 months from the end of treatment. At baseline, these men presented with lower serum FSH levels compared with those whose partners did not achieve pregnancy but not statistically significantly so. Although treatment with toremifene induced a statistically significant increase in FSH levels in both groups, FSH levels were statistically significantly lower (P<.05) in men whose partners achieved pregnancy at the end of the third month of treatment (see Fig. 1). We postulate that lower FSH levels in the men whose partners achieved pregnancy are due to a more functional negative feedback from the testes, thus reflecting better testicular response to treatment. This trend was also apparent in the higher levels of inhibin observed in the group of men whose partners eventually became pregnancy, although a level of statistical significance was not reached.
At baseline, no statistically significant differences in the three main semen parameters of sperm count, motility, and morphology were observed between men whose partners achieved pregnancy and those whose partners did not, although there was a trend for increased values in the former group. Notably, total sperm count as well as spermatozoa morphology was improved with toremifene administration; this change was more marked in the group of men whose partners achieved pregnancy (see Table 3, Fig. 3). Moreover, total sperm count and spermatozoa morphology at the end of treatment had statistically significant prognostic value for the achievement of pregnancy within the subsequent 2 months. This finding is again consistent with better testicular functional response in the subgroup of men whose partners achieved pregnancy.
Conclusively, the present study shows that toremifene administration for a period of 3 months in men with idiopathic oligozoospermia results in statistically significant improvements in all three main semen parameters of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. It is possible, therefore, that this particular SERM could be useful as an initial approach in the treatment of subfertile men with idiopathic oligozoospermia. Nevertheless, the precise standards of treatment need to be further investigated by randomized, placebo-controlled trials.
LakeMountD
Doctor Science
Lastly, this is the most important statement I saw:
"It should be noted that, although tamoxifen has also been shown to induce a statistically significant increase in spermatozoa count, this particular SERM has not been shown to induce any marked changes in motility and morphology (6) and (7)."
"It should be noted that, although tamoxifen has also been shown to induce a statistically significant increase in spermatozoa count, this particular SERM has not been shown to induce any marked changes in motility and morphology (6) and (7)."