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Science question for MS and others
- Thread starter Realgains
- Start date
Yes, I guess you could say they atrophy. High circulating or gonadal androgens cause a decrease in ovarian estrogen production which also leads to a decrease in SHBG. This means everything kinda shuts down. The normal cyclical fluctuations in reproductive hormones are lost and menstration ceases (yippeeee).
Clomid binds to receptors in a woman's the brain (but does NOT activate the receptor like estrogen would) so that her brain can't perceive her ovaries are making estrogen. Because her brain thinks her ovaries aren't making estrogen, it continues making more FSH. The FSH signals her ovaries to step up the production of more estrogen, causing her estrogen levels to rise higher than they normally would and to remain high for longer than usual. So I guess it depends on what you want to happen post cycle. If you want to get your estrogen levels back up quickly, then Clomid would work. However if I was coming off cycle, I would want to take advantage of my reduced estrogen levels for as long as possible and would avoid Clomid like the proverbial plague.
Clomid binds to receptors in a woman's the brain (but does NOT activate the receptor like estrogen would) so that her brain can't perceive her ovaries are making estrogen. Because her brain thinks her ovaries aren't making estrogen, it continues making more FSH. The FSH signals her ovaries to step up the production of more estrogen, causing her estrogen levels to rise higher than they normally would and to remain high for longer than usual. So I guess it depends on what you want to happen post cycle. If you want to get your estrogen levels back up quickly, then Clomid would work. However if I was coming off cycle, I would want to take advantage of my reduced estrogen levels for as long as possible and would avoid Clomid like the proverbial plague.
I will also add that increasing testosterone in females has what I would call a domino effect on estrogen metabolism at several levels. Aside from shutting down ovarian production of estrogen, the decrease in SHBG effectively means even more free testosterone floating around. Test also increases thyroid hormone (T3), which acts as an aromatase inhibitor in the ovaries (as opposed to drugs like Arimidex that merely act on peripheral aromatase). Some of the extra test will get converted to DHT which is a potent inhibitor of the estrogen receptors. There are many facets to androgen response in women. It's not just and "on" or "off" single target drug!
Thanx for the reply MS and I learned something....BUT....I was more concerned about a women being able to get her natural test levels back post cycle form full sized and properly functioning ovaries. So...what about clomid post cycle to help boost test production just like with a man?
RG
RG
Estradiol significantly inhibits both basal and LH stimulated testosterone production in women. Remember that in women, the vast majority of ovarian estrogen is derived from aromatization of testosterone secreted by the thecal cells. The production of this testosterone is therefore under feedback inhibition from locally produced estrogen. If you give a woman Clomid, you will invoke this negative feedback because of increased estrogen. You will also create a rise in SHBG which will additionally reduce free T levels. In the simplest language I can muster, it is a bad idea unless you desire a rapid rise in estrogen with an accompanying decrease in bioavailable T.
WarLobo said:Damn you make me all horny when you talk like that MS
RealG, all I could say was that I've never even considered using clomid as it is used to bring up test production in male nuts. Femals prduce test in a different area so I just knew it wouldn't be useful. And estrogen is always something to keep in check (balance)
I would also refer to MS's statement on the many effects TEST has on women, most of which are exactly what ya all want.
But about half of a females testosterone comes directly from the ovaries and half from the adrenal glands and other ares of the body like muscle tissue.
Nandi12 posted an abstract on the very same post up on the anabolic forum...hope he come down to discuss this matter...anyway the abstract stated that females on clomid were seen to have elevated levels of serum androgens and unbound testosterone.
A very good topic indeed!!! MS has been on a tear lately. I f-ing love it when she does this too. Since I am basically as ignorant as any guy when it comes to understanding a woman's hormone staus, I am enjoying this learning experience.
RG, I would love to hear what B. Roberts has to say as well.
This post has very good potential to make it to elite's hall of fame posts!!! Anyway, the way I look at it, a lot of good threads on this forum have definately been overlooked for Hall of Fame status.
BMJ
RG, I would love to hear what B. Roberts has to say as well.
This post has very good potential to make it to elite's hall of fame posts!!! Anyway, the way I look at it, a lot of good threads on this forum have definately been overlooked for Hall of Fame status.
BMJ
I also think this is an excellent topic, and one that should be explored to it's fullest. I honestly don't know for sure that clomid wouldn't work to bring up post cycle test levels in a female. Jacked women are very different from ordinary anovulatory women who are usually obese, inactive and hyperinsulemic! No one has ever done the studies..... The study that Nandi12 mentioned is intriguing, but it's very old and doesn't really answer the question. The line that nandi thought was important :
"Compared with normally ovulating controls, serum luteinizing hormone (LH), the ratio of LH to follicle-stimulating hormone (FSH), serum androgens, unbound testosterone, and unbound estradiol were elevated and sex hormone binding globulin-binding capacity (SHBG-BC) significantly lower in women receiving clomiphene"
is telling in many ways. A large percentage of anovulatory women (compared to normal ovulating women) are suffering from PCOS and other hyperinsulinemic states that also cause an increase in unbound testosterone. We don't know if those women had naturally high test levels or not before the clomid treatment. All we can say for sure is that there were hormonal differences between normal women and anovulatory. It may or may not be due to clomiphene treatment.
Compare that to some of the more recent studies:
The effect of follicle-maturing drugs on mid-cycle androgen levels in women with normal baseline levels.
Theoretically, clomiphene citrate or human menopausal gonadotropins might have a higher chance of inducing pregnancy per cycle were it not for the possible concomitant rise in androgens induced by these follicle-maturing drugs. In the present study, mid-cycle androgen levels were evaluated in anovulatory women with normal baseline early follicular levels who were treated with either clomiphene citrate or human menopausal gonadotropins. The only mid-cycle androgen to rise above the normal range was androstenedione. However, no negative effects of elevated androstenedione levels on pregnancy rates were apparent. THUS, AT LEAST IN WOMEN WITH NORMAL BASELINE ANDROGEN LEVELS, THE USE OF FOLLICLE-MATURING DRUGS DOES NOT APPEAR TO CAUSE A RISE IN ANDROGEN LEVELS EXCEPT FOR ANDROSTENEDIONE, and the rise in androstenedione at mid-cycle appears to have no adverse effect on conception.
The early luteal phase in successful and unsuccessful implantation after IVF-ET.
The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate or human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.
Different hormonal patterns in human menopausal gonadotropin-treated, clomiphene citrate-treated, and untreated conception cycles.
Serum concentrations of seven different hormones were analyzed during 189 singleton conception cycles. One hundred nine women were treated with human menopausal gonadotropin (hMG), 52 women received clomiphene citrate (CC), and 28 became pregnant spontaneously. Serum progesterone (P) levels in hMG-treated women started to increase on day 18 of the cycle and reached peak concentrations between days 28 and 32 of the cycle. Serum estradiol (E2) concentrations paralleled the P patterns. In hMG-treated women, there were significant correlations between serum E2 and P concentrations and the number of the mature follicles observed before ovulation (both P less than 0.01). CC-TREATED AND SPONTANEOUS CONCEPTION CYCLES REVEALED SIGNIFICANTLY LOWER SERUM LEVELS OF P, E2, TESTOSTERONE, 17 alpha-hydroxyprogesterone, and prolactin, compared with hMG-treated cycles (P less than 0.05).
Ultimately the only way we'll find out is if some brave women tries this and measures her baseline free T before cycle, after cycle without clomid, and after cycle with clomid treatment.
"Compared with normally ovulating controls, serum luteinizing hormone (LH), the ratio of LH to follicle-stimulating hormone (FSH), serum androgens, unbound testosterone, and unbound estradiol were elevated and sex hormone binding globulin-binding capacity (SHBG-BC) significantly lower in women receiving clomiphene"
is telling in many ways. A large percentage of anovulatory women (compared to normal ovulating women) are suffering from PCOS and other hyperinsulinemic states that also cause an increase in unbound testosterone. We don't know if those women had naturally high test levels or not before the clomid treatment. All we can say for sure is that there were hormonal differences between normal women and anovulatory. It may or may not be due to clomiphene treatment.
Compare that to some of the more recent studies:
The effect of follicle-maturing drugs on mid-cycle androgen levels in women with normal baseline levels.
Theoretically, clomiphene citrate or human menopausal gonadotropins might have a higher chance of inducing pregnancy per cycle were it not for the possible concomitant rise in androgens induced by these follicle-maturing drugs. In the present study, mid-cycle androgen levels were evaluated in anovulatory women with normal baseline early follicular levels who were treated with either clomiphene citrate or human menopausal gonadotropins. The only mid-cycle androgen to rise above the normal range was androstenedione. However, no negative effects of elevated androstenedione levels on pregnancy rates were apparent. THUS, AT LEAST IN WOMEN WITH NORMAL BASELINE ANDROGEN LEVELS, THE USE OF FOLLICLE-MATURING DRUGS DOES NOT APPEAR TO CAUSE A RISE IN ANDROGEN LEVELS EXCEPT FOR ANDROSTENEDIONE, and the rise in androstenedione at mid-cycle appears to have no adverse effect on conception.
The early luteal phase in successful and unsuccessful implantation after IVF-ET.
The hormonal milieu at embryo implantation after in-vitro fertilization was investigated. Superstimulation was accomplished with clomiphene citrate or human menopausal gonadotrophin (HMG) injections followed by ovulation induction with human chorionic gonadotrophin (HCG). Venous blood samples were drawn on days 2 and 8, the day of oocyte recovery being day 0. Fifteen women with successful implantation, defined as an ultrasound-verified pregnancy, were compared to 42 women with unsuccessful implantation, using a three-way analysis of variance. Oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) did not differ between the two groups. However, the ratios of oestradiol/progesterone and of testosterone/SHBG were significantly higher in the non-fertile cycles, both on day 2 and on day 8 (P less than 0.05). Furthermore, there was a highly significant decrease in oestradiol, progesterone and testosterone between days 2 and 8 in fertile as well as in non-fertile cycles (P less than 0.001) and a highly significant increase in SHBG from day 2 to day 8 in both groups (P less than 0.001). The higher testosterone/SHBG ratio in the non-pregnant women implies a relative hyperandrogenicity in this group that might have adversely affected the uterine receptivity.
Different hormonal patterns in human menopausal gonadotropin-treated, clomiphene citrate-treated, and untreated conception cycles.
Serum concentrations of seven different hormones were analyzed during 189 singleton conception cycles. One hundred nine women were treated with human menopausal gonadotropin (hMG), 52 women received clomiphene citrate (CC), and 28 became pregnant spontaneously. Serum progesterone (P) levels in hMG-treated women started to increase on day 18 of the cycle and reached peak concentrations between days 28 and 32 of the cycle. Serum estradiol (E2) concentrations paralleled the P patterns. In hMG-treated women, there were significant correlations between serum E2 and P concentrations and the number of the mature follicles observed before ovulation (both P less than 0.01). CC-TREATED AND SPONTANEOUS CONCEPTION CYCLES REVEALED SIGNIFICANTLY LOWER SERUM LEVELS OF P, E2, TESTOSTERONE, 17 alpha-hydroxyprogesterone, and prolactin, compared with hMG-treated cycles (P less than 0.05).
Ultimately the only way we'll find out is if some brave women tries this and measures her baseline free T before cycle, after cycle without clomid, and after cycle with clomid treatment.
WarLobo said:
Queen eh....
Okay Realgains thats enough
he he he... Seriously I respect MS as a person and could care less about her preference.If clomid does help get test levels back to normal in females post cycle then I think it has value in preventing post cycle muscle loss
Thing is I think that females hold onto more of their gains than men do.. has this been your observation Lobo?
As for the tapering ... I don't think it would work unless you tapered for months with ever decreasing low doses.
RG
MS, you made some good points about the abstract I posted. However, consider a few aspects of female physiology.
First, anabolic steroids are antigonadotropic in both sexes, as you well know. Women become anovulatory (my wife can attest to that!).
Clomid is designed to induce ovulation. FSH and LH are both required for ovulation to occur. FSH initiates follicular development and LH completes development and leads to ovulation. As you know, it is the enlarging follicular cells that secrete both testosterone, and estrogens. The estrogens come from the aromatization of testosterone and androstenedione. If the process of follicular development is interrupted there will be no ovarian production of testosterone and estrogens. (There will still be some testosterone produced by the adrenal glands, as well as estrogen from its aromatization). This can happen from disease, malnutrition, or anabolic steroids.
So no follicular development equals no (or little) estrogen or testosterone. Clomid remedies this problem by increasing the production of LH and FSH from the pituitary, leading to follicular growth, ovulation, and steroidogenesis.
This begs the question: well, if there is no estrogen how can clomid block that nonexistent estrogen to stimulate LH and FSH secretion?
It turns out that small amounts of estrogen at the pituitary level sensitize the pituitary to GnRH release from the hypothalamus. This GnRH stimulates the pituitary to release its LH and FSH, leading to a normal ovulatory cycle. Clomid is a SERM that exerts the same estrogenic action on the pituitary. (See below)
All this is compicated by the fact that SERMS and estradiol at high concentrations seem to inhibit LH and FSH release. Nevertheless, it is still the case that clomid can induce ovulation, leading to increased steroidogenesis, both of testosterone and its aromatization product estradiol.
Am J Physiol 1981 Feb;240(2):E125-30
Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro.
Adashi EY, Hsueh AJ, Bambino TH, Yen SS.
The direct effects of clomiphene citrate (Clomid), tamoxifen, and estradiol (E2) on the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in cultured anterior pituitary cells obtained from adult ovariectomized rats. Treatment of pituitary cells with Clomid or enclomid (10(-8) M) in vitro for 2 days resulted in a marked sensitization of the gonadotroph to GnRH as reflected by a 6.5-fold decrease in the ED50 of GnRH in terms of LH release from 2.2 x 10(-9) M in untreated cells to 3.6 x 10(-10) M. Treatment with E2 or Clomid also increased the sensitivity of the gonadotroph to GnRH in terms of FSH release by 4.3- and 3.3-fold respectively. Tamoxifen, a related antiestrogen, comparable to Clomid in terms of its ability to compete with E2 for pituitary estrogen receptors, was without effect on the GnRH-stimulated LH release at a concentration of 10(-7) M. Furthermore, tamoxifen, unlike Clomid, caused an apparent but not statistically significant inhibition of the sensitizing effect of E2 on the GnRH-stimulated release of LH. Our findings suggest that Clomid and its Enclomid isomer, unlike tamoxifen, exert a direct estrogenic rather than an antiestrogenic effect on cultured pituitary cells by enhancing the GnRH-stimulated release of gonadotropin.
First, anabolic steroids are antigonadotropic in both sexes, as you well know. Women become anovulatory (my wife can attest to that!).
Clomid is designed to induce ovulation. FSH and LH are both required for ovulation to occur. FSH initiates follicular development and LH completes development and leads to ovulation. As you know, it is the enlarging follicular cells that secrete both testosterone, and estrogens. The estrogens come from the aromatization of testosterone and androstenedione. If the process of follicular development is interrupted there will be no ovarian production of testosterone and estrogens. (There will still be some testosterone produced by the adrenal glands, as well as estrogen from its aromatization). This can happen from disease, malnutrition, or anabolic steroids.
So no follicular development equals no (or little) estrogen or testosterone. Clomid remedies this problem by increasing the production of LH and FSH from the pituitary, leading to follicular growth, ovulation, and steroidogenesis.
This begs the question: well, if there is no estrogen how can clomid block that nonexistent estrogen to stimulate LH and FSH secretion?
It turns out that small amounts of estrogen at the pituitary level sensitize the pituitary to GnRH release from the hypothalamus. This GnRH stimulates the pituitary to release its LH and FSH, leading to a normal ovulatory cycle. Clomid is a SERM that exerts the same estrogenic action on the pituitary. (See below)
All this is compicated by the fact that SERMS and estradiol at high concentrations seem to inhibit LH and FSH release. Nevertheless, it is still the case that clomid can induce ovulation, leading to increased steroidogenesis, both of testosterone and its aromatization product estradiol.
Am J Physiol 1981 Feb;240(2):E125-30
Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro.
Adashi EY, Hsueh AJ, Bambino TH, Yen SS.
The direct effects of clomiphene citrate (Clomid), tamoxifen, and estradiol (E2) on the gonadotropin-releasing hormone (GnRH)-stimulated release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in cultured anterior pituitary cells obtained from adult ovariectomized rats. Treatment of pituitary cells with Clomid or enclomid (10(-8) M) in vitro for 2 days resulted in a marked sensitization of the gonadotroph to GnRH as reflected by a 6.5-fold decrease in the ED50 of GnRH in terms of LH release from 2.2 x 10(-9) M in untreated cells to 3.6 x 10(-10) M. Treatment with E2 or Clomid also increased the sensitivity of the gonadotroph to GnRH in terms of FSH release by 4.3- and 3.3-fold respectively. Tamoxifen, a related antiestrogen, comparable to Clomid in terms of its ability to compete with E2 for pituitary estrogen receptors, was without effect on the GnRH-stimulated LH release at a concentration of 10(-7) M. Furthermore, tamoxifen, unlike Clomid, caused an apparent but not statistically significant inhibition of the sensitizing effect of E2 on the GnRH-stimulated release of LH. Our findings suggest that Clomid and its Enclomid isomer, unlike tamoxifen, exert a direct estrogenic rather than an antiestrogenic effect on cultured pituitary cells by enhancing the GnRH-stimulated release of gonadotropin.
I disagree with the assertion that “ no follicular development equals no (or little) estrogen or testosterone”. Indeed women with PCOS have relatively normal circulating estrogen (from peripheral aromatization) and high testosterone (which is mainly ovarian in origin), yet their follicles fail to develop normally. The theca cells of postmenopausal women also continue to produce testosterone in the complete absence of follicles or ovarian estrogen.
As I said, I don’t really know where juiced women fit into all of this and it would be nice if we had some ‘volunteers’. But I think WarLobo’s point about how relevant is it really is a good one. Post cycle estrogen rebound is a curse to BB women, and it doesn’t appear to take very long at all for ovarian estrogen secretion to return (often with a vengeance). Put another way, YOU would feel bad if you went from having the androgen levels of an 18 year old male down to having the androgen and estrogen levels of a 30 year old female. Why would a woman feel any better, even IF the Clomid brought her T levels up to that of a ‘normal’ female more quickly. It’s still a huge drop from where she was. I can’t see how any amount of tapering can help. It just sucks to be a female BB off cycle!
I think all of this stuff about being a ‘Queen’ went right over my head. WarLobo used to call me the Queen of the long posts LOL.
As I said, I don’t really know where juiced women fit into all of this and it would be nice if we had some ‘volunteers’. But I think WarLobo’s point about how relevant is it really is a good one. Post cycle estrogen rebound is a curse to BB women, and it doesn’t appear to take very long at all for ovarian estrogen secretion to return (often with a vengeance). Put another way, YOU would feel bad if you went from having the androgen levels of an 18 year old male down to having the androgen and estrogen levels of a 30 year old female. Why would a woman feel any better, even IF the Clomid brought her T levels up to that of a ‘normal’ female more quickly. It’s still a huge drop from where she was. I can’t see how any amount of tapering can help. It just sucks to be a female BB off cycle!
I think all of this stuff about being a ‘Queen’ went right over my head. WarLobo used to call me the Queen of the long posts LOL.
1) High circulating concentrations of androgens will cause histological changes in the female reproductive tract. See the women to men transsexual literature.
2) Why not just bridge cycles with a low dose of T-gel and forget about the clomid. Seems to me that firing up the ovaries with clomid, while increasing T concentrations to a small degree also increases estrogen and the risk of preganancy and/or ovarian hyperstimulation.
I would think that a low dose of T would be far safer (side-effects) and more effective at maintaining gains, feeling of well-being, libido, etc., than clomid in women, not to mention less expensive.
W6
2) Why not just bridge cycles with a low dose of T-gel and forget about the clomid. Seems to me that firing up the ovaries with clomid, while increasing T concentrations to a small degree also increases estrogen and the risk of preganancy and/or ovarian hyperstimulation.
I would think that a low dose of T would be far safer (side-effects) and more effective at maintaining gains, feeling of well-being, libido, etc., than clomid in women, not to mention less expensive.
W6
Well, previously you criticized me for reproducing an abstract dealing with potentially ovarian dysfunctional women, and now you are invoking PCOS patients to make your point?
As far as post menopausal women go, we both know that estrogen and androgen levels are so low as to present health risks to women. This is obviously why these women are treated with estrogens and often an estrogen/methyltestosterone combination (Estratest). What the clomid is doing by virtue of inducing ovulation is restoring hormonal levels to what they should be in a healthy premenopausal woman.
wilson6 said:
It would certainly help with maintaining gains, sex drive and feelings of feel being but what I am concerned about is getting the females test levels back to normal with properly functioning ovaries.
What you ae saying is akin to men using low dose test post cycle and in both situations normal natural test production will not be allowed to resume thus cauing further atrophy of the gonads
RG
.
I had the opportunity to talk to my sister-in-law about this. She is a researcher in in vitro fertilization in primates. Her take on it was that theoretically clomid treatment should work, but in practice clomid has a high failure rate of inducing ovulation. She would use r-FSH if she wanted to jumpstart normal cycling. She does this in monkeys routinely to induce cycling so she can harvest eggs. Admittedly though, she has never tried it in a monkey coming off a cycle of steroids.
Nandi12, I was not turning the tables on you. I was using PCOS as an illustration of how neither estrogen nor follicles are required for a woman to make ovarian Test. My comments were to get everyone to ask the obvious question which has not yet been asked here which is "does ovarian production of testosterone decline with exogenous supplementation"? Everyone has assumed that it does but the cases of PCOS and postmenopausal women should illustrate that this is not necessarily the case. Post menopausal women suffer from a decrease in circulating androgens, but ovarian output does not decrease significantly even in the complete absence of ovarian estrogen. Postmenopausal women do not necessarily have an absolute deficiency in testosterone unless they have other pathological conditions or are on HRT. It's also interesting that postmenopausal ovaries lose their receptors for LH and FSH so that they can no longer respond to these signals. I'm not sure how different (or similar) women coming off of AAS would be form postmenopausal women. Also if you look at the perimenopausal period you'll find that LH and FSH levels are elevated but free test and andro levels actually drop (only to rise again after complete menopause). Additionally if you give test to postmenopausal women, it has no effect on their LH or FSH output. All in all I seriously doubt that clomid would make a large difference but that is pure speculation.
Maybe you should ask your sister-in-law to give those lucky primates a cycle of test and then try the clomid on them. The question that realgains originally wanted to know was whether it would elevate free T faster or higher than no clomid treatment and the only way we'll know for sure (though we can speculate all we want) is to try it! When I first read his question (about test levels) I have to admit that I kinda chuckled at the notion that it could make a big difference purely because we're talking about such low levels to begin with in normal women. A 20% increase of normal female levels of test is still pathologically low if you've just come off of a decent cycle, and I don't really believe that clomid would even have a 20% impact. Aside from that, I don't know for sure that women coming off cycle actually suffer from pathologically low test. All in all women are a lot more complicated than men
when it comes to gonadal and adrenal hormones.
Maybe you should ask your sister-in-law to give those lucky primates a cycle of test and then try the clomid on them. The question that realgains originally wanted to know was whether it would elevate free T faster or higher than no clomid treatment and the only way we'll know for sure (though we can speculate all we want) is to try it! When I first read his question (about test levels) I have to admit that I kinda chuckled at the notion that it could make a big difference purely because we're talking about such low levels to begin with in normal women. A 20% increase of normal female levels of test is still pathologically low if you've just come off of a decent cycle, and I don't really believe that clomid would even have a 20% impact. Aside from that, I don't know for sure that women coming off cycle actually suffer from pathologically low test. All in all women are a lot more complicated than men
when it comes to gonadal and adrenal hormones.At the risk of putting words in your mouth, MS, it seems like you are saying either that
a) exogenous androgens do not have an effect on LH and/or FSH secretion in women
b) Ovarian androgen production is not under the control of LH and/or FSH
Please correct me if I am misinterpreting your thesis.
I will admit that there is a striking lack of studies on the effects of androgen administration in women, no doubt for ethical reasons. There is a lot of indirect evidence however that both (a) and (b) are not correct.
For instance, in eugonadal female to male transsexuals,
"Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02)." (1)
So exogenous test seems to depress LH and FSH secretion, at least in this study of female to male transsexuals with intact ovaries.
This addresses at least part of your question. One could still argue that this does not say anything about the effects of lowered LH and FSH on ovarian test production.
If ovarian androgens are not under the control of LH and/or FSH, how would one explain the large amount of research showing that both HRT and oral contraceptives lower serum testosterone levels in women? To quote from recent study,
"Free testosterone decreased 49% in women taking E2 replacement as compared to a 7% decline in women taking placebo." (2) It is my understanding that oral contraceptives work primarily by lowering gonadotropin levels, which blocks follicular development and ovulation.
Also, PCOS is a bad example for this discussion because the normal feedback/forward mechanisms involving steroids, gonadotropins, and GnRH are deranged:
"Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens" (3)
(1) J Clin Endocrinol Metab 1989 Jul;69(1):151-7
The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects.
Spinder T, Spijkstra JJ, van den Tweel JG, Burger CW, van Kessel H, Hompes PG, Gooren LJ.
(2) J Reprod Med 2001 Dec;46(12):1052-6
Comparison of estrogen and androgen levels after oral estrogen replacement therapy.
Slater CC, Zhang C, Hodis HN, Mack WJ, Boostanfar R, Shoupe D, Paulson RJ, Stanczyk FZ.
(3) Arch Med Res 2001 Nov-Dec;32(6):544-52
Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome.
Barontini M, Garcia-Rudaz MC, Veldhuis JD.
a) exogenous androgens do not have an effect on LH and/or FSH secretion in women
b) Ovarian androgen production is not under the control of LH and/or FSH
Please correct me if I am misinterpreting your thesis.
I will admit that there is a striking lack of studies on the effects of androgen administration in women, no doubt for ethical reasons. There is a lot of indirect evidence however that both (a) and (b) are not correct.
For instance, in eugonadal female to male transsexuals,
"Long term T treatment in the nine female to male transsexual subjects resulted in increases in the mean serum T level from 1.7 +/- 0.8 (+/- SD) to 40.8 +/- 31.9 nmol/L (P less than 0.01), the mean serum dihydrotestosterone level from 0.6 +/- 0.2 to 3.3 +/- 1.5 nmol/L (P less than 0.02), and the mean serum free T level from 9.5 +/- 5.2 to 149 +/- 46 pmol/L (P less than 0.02). Mean serum estrone and estradiol levels were similar before and during T treatment. The mean serum LH level decreased from 6.3 +/- 2.0 to 2.9 +/- 1.1 U/L (P less than 0.01), and the mean FSH levels decreased from 6.6 +/- 2.0 to 3.7 +/- 2.2 U/L (P less than 0.02)." (1)
So exogenous test seems to depress LH and FSH secretion, at least in this study of female to male transsexuals with intact ovaries.
This addresses at least part of your question. One could still argue that this does not say anything about the effects of lowered LH and FSH on ovarian test production.
If ovarian androgens are not under the control of LH and/or FSH, how would one explain the large amount of research showing that both HRT and oral contraceptives lower serum testosterone levels in women? To quote from recent study,
"Free testosterone decreased 49% in women taking E2 replacement as compared to a 7% decline in women taking placebo." (2) It is my understanding that oral contraceptives work primarily by lowering gonadotropin levels, which blocks follicular development and ovulation.
Also, PCOS is a bad example for this discussion because the normal feedback/forward mechanisms involving steroids, gonadotropins, and GnRH are deranged:
"Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens" (3)
(1) J Clin Endocrinol Metab 1989 Jul;69(1):151-7
The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects.
Spinder T, Spijkstra JJ, van den Tweel JG, Burger CW, van Kessel H, Hompes PG, Gooren LJ.
(2) J Reprod Med 2001 Dec;46(12):1052-6
Comparison of estrogen and androgen levels after oral estrogen replacement therapy.
Slater CC, Zhang C, Hodis HN, Mack WJ, Boostanfar R, Shoupe D, Paulson RJ, Stanczyk FZ.
(3) Arch Med Res 2001 Nov-Dec;32(6):544-52
Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome.
Barontini M, Garcia-Rudaz MC, Veldhuis JD.
We know what happens to guys, we don't know what happens to women and that is what this discussion is about.
Personally, I think 500 - 1000 IU 2x/wk of hCG during a cycle with clomid post-cycle is the best way to go for guys. It has been shown in the lit that keeping hCG in the cycle while on test will preserve testicular function.
The question is what happens with women. Having asked that, there are a number of women who have juiced for years then gone on to have kids, but why bet the farm on that. If you're planning on having kids and are female, then common sense would suggest to wait until after having kids if you're bent on juicing? What is so strange about that concept?
Guys are a different story. We know that with purdent use of hCG and clomid, fertility can be preserved. Even in some worst case situations, fertility can be restored.
W6
Personally, I think 500 - 1000 IU 2x/wk of hCG during a cycle with clomid post-cycle is the best way to go for guys. It has been shown in the lit that keeping hCG in the cycle while on test will preserve testicular function.
The question is what happens with women. Having asked that, there are a number of women who have juiced for years then gone on to have kids, but why bet the farm on that. If you're planning on having kids and are female, then common sense would suggest to wait until after having kids if you're bent on juicing? What is so strange about that concept?
Guys are a different story. We know that with purdent use of hCG and clomid, fertility can be preserved. Even in some worst case situations, fertility can be restored.
W6
wilson6 said:
I appreciate your comments W6 ....but we do indeed know what happens to females during AAS cycling. They have a major reduction in estrogen, progesterone and test production AND their ovaries atrophy in the same way a man testes artophy.
I would agree with you that perhaps its best to avoid AAS if you want to get pregant in the future cause its hard enough for many to get pregant having very tinkered with their gonads. Ovaries are very similar to testes in many respects.
Speaking if H C G ....I wonder what affect that would have on a female. Perhaps it would be a good idea for a women to take a little H C G mid cycle to prevent trophy of her ovaries.....after all wasn't H C G developed for females.
RG
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"....but we do indeed know what happens to females during AAS cycling. They have a major reduction in estrogen, progesterone and test production AND their ovaries atrophy in the same way a man testes artophy."
OK, first of all, where is this published?
Before we go any further with this, check out the following references.
Endocrine effects in female weight lifters who self-administer testosterone and anabolic steroids by Marlarkey et al., Am J Obstet Gynecol, 1991.
There is considerable variation in the response to AAS use in women. Estradiol was not decreased even in those women on non-aromatizable androgens, LH was unchanged, FSH decreased in some but not all users. In fact, in one subject with a blood test conc. of over 1100 ng/dl, her LH, FSH and E2 were normal. She had used AAS for over 7 yrs and was combining 4 different drugs at the time of her blood work.
Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals by Elbers et al., Am J Physiol 276, 1999.
Decreased LH at 4 mo of T (250 mg/2 wk) but not at 2 mo. No change in FSH with up to a year treatment.
Also check out,
Androgen Administration to Transsexual Women by Heresova et al., Exp. Clin. Endocrinol. 88, 1986.
Chronic high-dosage androgen administration to ovulatory women does not alter adrenocortical steroidogenesis by Futterweit et al., Fertil Steril. 58, 1992.
Histological changes in the genital tract in transsexual women following androgen therapy by Miller et al., Histopathology 10, 1986.
Ovarian Cancer in Female-to-Male Transsexuals: Report of two cases by Hage et al., Gynecol Oncol. 76, 2000.
Good mechanisms described in the discussion section of the above paper.
Based on these papers, I'd say we don't know what's happening. Some idea perhaps, but certainly not conclusive. There is way too much individual variation depending on the drug, dose, duration of use and individual response.
In some cases they may be little to no change in endocrine function and ovarian histology and in others, major long-term changes in endocrine function and permanent changes in ovarian structure and function.
In guys, the use of hCG and clomid for post-AAS use recovery is well established and relatively void of significant side-effects. In women, we don't know what it will really do or if it is even necessary.
Besides, ovarian function is supressed during OC use as is endogenous testosterone production. It isn't common to prescribe clomid or hCG following OC use, thus why should it be any different following an AAS cycle?
W6
OK, first of all, where is this published?
Before we go any further with this, check out the following references.
Endocrine effects in female weight lifters who self-administer testosterone and anabolic steroids by Marlarkey et al., Am J Obstet Gynecol, 1991.
There is considerable variation in the response to AAS use in women. Estradiol was not decreased even in those women on non-aromatizable androgens, LH was unchanged, FSH decreased in some but not all users. In fact, in one subject with a blood test conc. of over 1100 ng/dl, her LH, FSH and E2 were normal. She had used AAS for over 7 yrs and was combining 4 different drugs at the time of her blood work.
Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals by Elbers et al., Am J Physiol 276, 1999.
Decreased LH at 4 mo of T (250 mg/2 wk) but not at 2 mo. No change in FSH with up to a year treatment.
Also check out,
Androgen Administration to Transsexual Women by Heresova et al., Exp. Clin. Endocrinol. 88, 1986.
Chronic high-dosage androgen administration to ovulatory women does not alter adrenocortical steroidogenesis by Futterweit et al., Fertil Steril. 58, 1992.
Histological changes in the genital tract in transsexual women following androgen therapy by Miller et al., Histopathology 10, 1986.
Ovarian Cancer in Female-to-Male Transsexuals: Report of two cases by Hage et al., Gynecol Oncol. 76, 2000.
Good mechanisms described in the discussion section of the above paper.
Based on these papers, I'd say we don't know what's happening. Some idea perhaps, but certainly not conclusive. There is way too much individual variation depending on the drug, dose, duration of use and individual response.
In some cases they may be little to no change in endocrine function and ovarian histology and in others, major long-term changes in endocrine function and permanent changes in ovarian structure and function.
In guys, the use of hCG and clomid for post-AAS use recovery is well established and relatively void of significant side-effects. In women, we don't know what it will really do or if it is even necessary.
Besides, ovarian function is supressed during OC use as is endogenous testosterone production. It isn't common to prescribe clomid or hCG following OC use, thus why should it be any different following an AAS cycle?
W6
Yes, as Wilson6 so clearly illustrated, women really ARE more complicated then men.
Nandi12, free T goes down with HRT or OC because of an increase in SHBG. This is a well established correlation and has nothing to do with endogenous T production. This seems to be why OC are useful in reducing circulating T in women with PCOS even with their 'hormonal derangement'. This is also the reason why postmenopausal women on HRT benefit from some extra test, but women who don't take HRT are not as prone to problems with low test.
" At the risk of putting words in your mouth, MS, it seems like you are saying either that
a) exogenous androgens do not have an effect on LH and/or FSH secretion in women
b) Ovarian androgen production is not under the control of LH and/or FSH
Please correct me if I am misinterpreting your thesis. "
Yes you misinterpreted me. I was attempting to illustrate that exogenous androgens do not NECESSARILY have an affect on LH/FSH, and that ovarian androgen production in not NECESSARILY under the direct control of LH/FSH. I was basically trying to get someone to come up with evidence that androgen administration to women with intact ovaries would inevitably result in decreased endogenous T production, and even if it did, that Clomid would reliably or significantly bring these hypothetically low T levels back up to normal more quickly than without Clomid.
"Also, PCOS is a bad example for this discussion because the normal feedback/forward mechanisms involving steroids,
gonadotropins, and GnRH are deranged: " Again, I was only using PCOS women as an example that we can not assume anything about the feedback regulation of endogenous T production in women, but it is certainly interesting that in that same paper you mentioned involving the female to male transsexuals, the investigators found a striking similarity in the histopathology of the ovaries of transsexuals on T replacement compared to women with PCOS. Also in both groups, estrogen levels remained normal but T levels were above normal. I see no indication from that paper (or any others that have been reviewed here) that we should expect a post cycle 'crash' in women coming off AAS or that clomid would be in any way helpful. But it's all academic and as always, Wilson6's advice is sound and practical, though I personally wouldn't worry about post cycle crash in women.
Nandi12, free T goes down with HRT or OC because of an increase in SHBG. This is a well established correlation and has nothing to do with endogenous T production. This seems to be why OC are useful in reducing circulating T in women with PCOS even with their 'hormonal derangement'. This is also the reason why postmenopausal women on HRT benefit from some extra test, but women who don't take HRT are not as prone to problems with low test.
" At the risk of putting words in your mouth, MS, it seems like you are saying either that
a) exogenous androgens do not have an effect on LH and/or FSH secretion in women
b) Ovarian androgen production is not under the control of LH and/or FSH
Please correct me if I am misinterpreting your thesis. "
Yes you misinterpreted me. I was attempting to illustrate that exogenous androgens do not NECESSARILY have an affect on LH/FSH, and that ovarian androgen production in not NECESSARILY under the direct control of LH/FSH. I was basically trying to get someone to come up with evidence that androgen administration to women with intact ovaries would inevitably result in decreased endogenous T production, and even if it did, that Clomid would reliably or significantly bring these hypothetically low T levels back up to normal more quickly than without Clomid.
"Also, PCOS is a bad example for this discussion because the normal feedback/forward mechanisms involving steroids,
gonadotropins, and GnRH are deranged: " Again, I was only using PCOS women as an example that we can not assume anything about the feedback regulation of endogenous T production in women, but it is certainly interesting that in that same paper you mentioned involving the female to male transsexuals, the investigators found a striking similarity in the histopathology of the ovaries of transsexuals on T replacement compared to women with PCOS. Also in both groups, estrogen levels remained normal but T levels were above normal. I see no indication from that paper (or any others that have been reviewed here) that we should expect a post cycle 'crash' in women coming off AAS or that clomid would be in any way helpful. But it's all academic and as always, Wilson6's advice is sound and practical, though I personally wouldn't worry about post cycle crash in women.
It's disappointing that we ended up with so many conflicting studies. I find it difficult to believe that womens' responses to anabolic steroids are random, as Wilson's post about weight lifters suggests. Surely there is a fundamental mechanism common to all women that controls the relationships between gonadotropins and steroidal hormones. Women may be more complex, but not to the point of randomness.
Also MS, oral contraceptives do lower total testosterone but this effect may be due to the feedback inhibition on ovarian androgen production by the progestin component of the regimen. To quote from just a couple of studies:
"The decrease in serum androgens with total testosterone (by 17 and 40%), free testosterone (by 48 and 54%) and dehydroepiandrosterone sulfate (by 51%) corresponds to the values shown in the literature for other oral contraceptives with modern progestins." (1)
"There was also a significant decrease in the levels of total testosterone by 30-35% (p < 0.01) and free testosterone by 60% (p < 0.01), while sex hormone-binding globulin (SHBG) was increased by 200-240% on days 11 and 21 (p < 0.01)." (2)
Since progestins vary in their intrinsic androgenicity, it is not clear to me whether this as a purely progestigeneic or androgenic effect.
Regarding estrogen's ability to lower ovarian androgen secretion, this phenomenon is discussed in virtually every pharmacology text. I pulled one off my shelf that I use routinely, Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. 1990. The entry on page 1394 on acne treatment is as a succinct description of estrogen's effects as I have seen:
"Treatment with estrogen is effective in both sexes by suppressing gonadotropins and gonadal androgen secretion, but its usefulness in the male is obviously limited"
(1) Zentralbl Gynakol 1997;119(12):597-606
[Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations]
Oettel M, Carol W, Graser T, Klinger G, Mellinger U, Moore C, Schindler AE, Winkler UH.
(2)Contraception 1995 Jun;51(6):341-6
Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins.
Wiegratz I, Jung-Hoffmann C, Kuhl H.
Also MS, oral contraceptives do lower total testosterone but this effect may be due to the feedback inhibition on ovarian androgen production by the progestin component of the regimen. To quote from just a couple of studies:
"The decrease in serum androgens with total testosterone (by 17 and 40%), free testosterone (by 48 and 54%) and dehydroepiandrosterone sulfate (by 51%) corresponds to the values shown in the literature for other oral contraceptives with modern progestins." (1)
"There was also a significant decrease in the levels of total testosterone by 30-35% (p < 0.01) and free testosterone by 60% (p < 0.01), while sex hormone-binding globulin (SHBG) was increased by 200-240% on days 11 and 21 (p < 0.01)." (2)
Since progestins vary in their intrinsic androgenicity, it is not clear to me whether this as a purely progestigeneic or androgenic effect.
Regarding estrogen's ability to lower ovarian androgen secretion, this phenomenon is discussed in virtually every pharmacology text. I pulled one off my shelf that I use routinely, Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. 1990. The entry on page 1394 on acne treatment is as a succinct description of estrogen's effects as I have seen:
"Treatment with estrogen is effective in both sexes by suppressing gonadotropins and gonadal androgen secretion, but its usefulness in the male is obviously limited"
(1) Zentralbl Gynakol 1997;119(12):597-606
[Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations]
Oettel M, Carol W, Graser T, Klinger G, Mellinger U, Moore C, Schindler AE, Winkler UH.
(2)Contraception 1995 Jun;51(6):341-6
Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins.
Wiegratz I, Jung-Hoffmann C, Kuhl H.
*Sigh*. What are we actually trying to establish with this discussion. From the outset (when I finally understood realgains actual question about restoring T) I said:
"Estradiol significantly inhibits both basal and LH stimulated testosterone production in women. Remember that in women, the vast majority of ovarian estrogen is derived from aromatization of testosterone secreted by the thecal cells. The production of this testosterone is therefore under feedback inhibition from locally produced estrogen. If you give a woman Clomid, you will invoke this negative feedback because of increased estrogen. You will also create a rise in SHBG which will additionally reduce free T levels.................."
This is not in dispute. As you say, it is a well known fact that estrogens inhibit ovarian T production, though it's a relatively small effect compared to the increase in SHBG mediated free T reduction, and is virtually a non-issue in PCOS and postmeno women. The question I was trying to answer was "would clomid increase free T levels post cycle". I have no doubt that clomid will increase ovarian estrogen secretion, but I have not seen anything to convince me that this will lead to and increase in free T in post cycle women. Nor have I seen anything to convince me that free T will be depressed in these women in the first place. I believe that the main action of FSH on follicular maturation is it's ability to upregulate local aromatase activity rather than any direct ability to increase excess T. FSH in women is largely responsible for converting a predominantly androgenic environment into an estrogenic one provided the appropriate substrates are available.
As a person who feels pretty strongly that it's inadvisable to take drugs that may not work for conditions that you may not even have, I still don't see the point in women taking clomid for this purpose. The worst case scenario is that the clomid will actually increase estrogen without a corresponding increase in T secretion that would be large enough to compensate for the extra SHBG. The best case scenario????
I guess you don't have a girlfriend/wife if you don't believe a woman's response can be totally unpredictable and random
"Estradiol significantly inhibits both basal and LH stimulated testosterone production in women. Remember that in women, the vast majority of ovarian estrogen is derived from aromatization of testosterone secreted by the thecal cells. The production of this testosterone is therefore under feedback inhibition from locally produced estrogen. If you give a woman Clomid, you will invoke this negative feedback because of increased estrogen. You will also create a rise in SHBG which will additionally reduce free T levels.................."
This is not in dispute. As you say, it is a well known fact that estrogens inhibit ovarian T production, though it's a relatively small effect compared to the increase in SHBG mediated free T reduction, and is virtually a non-issue in PCOS and postmeno women. The question I was trying to answer was "would clomid increase free T levels post cycle". I have no doubt that clomid will increase ovarian estrogen secretion, but I have not seen anything to convince me that this will lead to and increase in free T in post cycle women. Nor have I seen anything to convince me that free T will be depressed in these women in the first place. I believe that the main action of FSH on follicular maturation is it's ability to upregulate local aromatase activity rather than any direct ability to increase excess T. FSH in women is largely responsible for converting a predominantly androgenic environment into an estrogenic one provided the appropriate substrates are available.
As a person who feels pretty strongly that it's inadvisable to take drugs that may not work for conditions that you may not even have, I still don't see the point in women taking clomid for this purpose. The worst case scenario is that the clomid will actually increase estrogen without a corresponding increase in T secretion that would be large enough to compensate for the extra SHBG. The best case scenario????
I guess you don't have a girlfriend/wife if you don't believe a woman's response can be totally unpredictable and random
