Gyno just before PCT

OK so I never get any gyno issues and just as I am nearing the end of my cycle I started noticing puffiness. Started Letro at 2.5mg/day and Kessar at 20mg/day from Monday (this is when I noticed it). My PCT starts in 9 days. I felt around the nipple area. No lumps or bumps, but the nipples are puffy.

Do I run Letro on its own for 2 - 3 months then follow up with HCG and Kessar as PCT?

or

Do I run Letro through PCT, taper off about 2 weeks before PCT ends and just continue with Kessar?

or What should I do?

milktuds wrote:

OK so I never get any gyno issues and just as I am nearing the end of my cycle I started noticing puffiness. Started Letro at 2.5mg/day and Kessar at 20mg/day from Monday (this is when I noticed it). My PCT starts in 9 days. I felt around the nipple area. No lumps or bumps, but the nipples are puffy.

Do I run Letro on its own for 2 - 3 months then follow up with HCG and Kessar as PCT?

or

Do I run Letro through PCT, taper off about 2 weeks before PCT ends and just continue with Kessar?

or What should I do?

What was your cycle?

Did you have a nor test in it?

Prop(8 weeks), Var(5 weeks), Masteron(6 weeks)

milktuds wrote:

Prop(8 weeks), Var(5 weeks), Masteron(6 weeks)

Have you stopped the masteron already? If so, why did you only run the masteron for 6 weeks but the cycle was 8 weeks-was it masteron prop, not an enanthate ester?

Masteron will act as an anti E and limit the estrogen effects from testosterone aromatisation, so I would have used it right through the cycle.

Right now I'd use the nolva to block the receptors to stop the estrogen being soaked up by the body. If you were using masteron prop, start using it again until the cycle has finished.

Then start letrozole anti gyno protocol if it is still there.

I have a thread on gyno reversal I'll post

This is it-taken from another site, extract from C-Bino and Nark.

Very long, but interesting and has letro gyno reversal protocol.

If you're using nolva with letro, must bear in mind nolva reduces the efficacy of letro by 37%.


GYNO prevention and reversal
again I took this from another site, but I thought it was very informative.

All you need to know about GYNO. written by C-bino and Nark

I am posting this thread to help answer all of the questions regarding gyno prevention and reversal, the use of letrozole and other anti-e’s. I will go over everything in very simple easy to understand language. Also we are talking about estrogen gyno here, not progesterone (but using letro will stop progesterone related problems as well since it inhibits all estrogen anyways). Progesterone gyno will be enlargement of your nipple area, the actual aereola, not a lump under it.

Let me make this first point very clear, as I state in my signature this is from my personal experience, so whether you agree with it or not is your own issue. I have helped many people with gyno and it has worked just fine for them as well.

To first understand why you are doing what you are doing I am going to go over a few things and a few definitions:

SERM – Selective estrogen receptor modulator. These drugs work by binding to the estrogen receptors and flooding them in a sense, making it difficult (but not impossible by any means) for estrogen to bind to the receptors and thus prevent the onset of estrogen related side effects.
Most common forms: Tamoxifen (Nolvadex), Clomiphene (Clomid)
AI – Aromatise Inhibitor. These drugs work by inhibiting the aromatization of estrogen. This means that in effect AI’s prevent androgens from converting to estrogen, again, making it difficult (but not impossible) for estrogen to reach receptor sites.
Most common forms: Anastrozole (l-dex, a-dex), Exemestane (aromasin), Femera (letrozole). For our purpose of reversing gyno we are interested in Letro.

Letro and your sex drive:
Letrozole will suppress your sex drive. This is another reason why it is so important to act on preventing gyno as soon as possible. Since we all know that Test should be run in every cycle this will cancel out the effect of sex drive suppression.

Running letro to prevent gyno:
If you decide to run estrogen protection while on cycle (and I suggest you do unless you are aware that you do not require it), you can run either a SERM or an AI. Letro will be the most powerful AI you can use, it will inhibit 98+% of estrogen using a dose as low as .25mg and even lower. This is why I suggest you do not use a dose higher than .50mg while on cycle just trying to prevent estrogen related side effects.

You will want to start running the letro approximately 2 weeks before you begin your cycle to allow it to fully stabilize in your blood. I have often heard the argument that letro takes up to 60 days to stabilize, I don’t know if I buy into this for the reason that I have reversed gyno after using letro for only 1 week. Still to be safe I recommend starting it before your cycle as stated above.

If you do decide to run letro there is absolutely no need to run another AI or SERM. Do not make the mistake of thinking more is better. Think of it this way; if letro is preventing the conversion of androgens to estrogen than there is no estrogen, what would the purpose of a SERM be when there is no estrogen to bind to the receptors? Nolva will only take away from the effectiveness of letro.

This brings me to my next point. Do not listen to anyone who tells you to bump up your nolvadex to 60+mg ED if you get gyno. I have no idea where this idea started but I have seen it suggest far too many times recently. Nolvadex will do nothing to reverse your gyno…let me make that clear IT WILL DO NOTHING FOR GYNO. If you are running nolva as your anti-e and start to develop gyno than sure you can bump the dosage a small amount to try to prevent it from progressing further, but letrozole must begin ASAP.

It is very important that you begin taking letrozole immediately, the longer your wait the more risk you take in not being able to reverse it.

How do I know if I have gyno?
If you have developed gyno you will have a lump behind your nipple. It will be fairly hard, and it will be tender to touch.

Running letro to reverse gyno:
I am going to go over the three different scenarios which people could fit into. Remember regardless of what scenario you are in it is important that you begin taking the letro ASAP.

1. Already using an anti-e aside from letro.
2. Already using letro @ a dose of .25mg or .50mg ED.
3. Not running any estrogen protection.

1.
Day 1: .25mg Letro + anti-e*
Day 2: .50mg Letro
Day 3: 1.0mg Letro
Day 4: 1.5mg Letro
Day 5: 2.0mg Letro
Day 6: 2.5mg Letro **

2.
Day 1: .50mg Letro
Day 2: 1.0mg Letro
Day 3: 1.5mg Letro
Day 4: 2.0mg Letro
Day 5: 2.5mg Letro **

3.
Day 1: .50mg Letro
Day 2: 1.0mg Letro
Day 3: 1.5mg Letro
Day 4: 2.0mg Letro
Day 5: 2.5mg Letro **

*Regardless of the anti-e you are using it is important to still use it for the first day you begin letro as the letro will not have taken any effect and you by no means want your body to be without any protection when gyno is already prevalent.

** You will remain at this dose until gyno symptoms subside. Once you believe your gyno is gone it is important to stay at this dose for another 4-7 days to ensure all traces are gone. I recommend people with a bf% over 15 stay on for a week as it may be harder to judge completely whether the lump is completely gone. Once this period is over it will be important to taper letro down slowly rather than coming off it completely. Regardless of which manner you tapered up your dose you will all taper down in the same fashion.

Day 1: 2.0mg
Day 2: 1.5mg
Day 3: 1.0mg
Day 4: .50mg***
Day 5: .25mg
***You can remain at this dose or go down further to .25mg. It is really up to you at this point. They are both very common maintenance doses as an anti-e while on cycle. Personally I have stayed with .25mg and never had a problem.

Letro and the estrogen rebound:
With your estrogen being completely inhibited there is a definite estrogen rebound as your body tries to re-stabilize the testosterone:estrogen balance. We can prevent this rebound effect by supplementing further with another AI or SERM. So, I suggest that when you are coming to the end of your cycle you will more than likely be using Nolva in your PCT so just make sure that you begin taking nolva the last day you are going to take your letro and then continue on as you would with regular PCT.

This now leads us into the question of reversing gyno while not on cycle. There are a few things to remember here. You have already waited longer than you should have, and your sex drive will be shot. You can use tribulus or another natural test booster to help you in this scenario but I can’t guarantee the effectiveness. Just follow gyno reversal protocols 2 or 3. When coming off again you must taper and begin using nolvadex to prevent any rebound effect that may occur.

How much nolvadex should you use if you are not going into PCT and running this off cycle? I suggest starting at 20mg ED for a week and then lowering it to 10mg for another week and then coming off completely.

I hope this covers most of the issues, still feel free to PM me if you have questions. But make sure you read the entire post first.

Gynecomastia: Etiology, Diagnosis, And Treatment

GYNECOMASTIA: ETIOLOGY, DIAGNOSIS, AND TREATMENT
Chapter 14 - Ronald S. Swerdloff, MD, Jason Ng, MD, and Gladys E. Palomeno, MD,
March 1, 2004

In this thread we will review: the ontogeny and physiology of breast development; factors that influence breast enlargement in the male; the differential diagnosis of gynecomastia; the process of diagnostic investigation; and treatment of gynecomastia.

BREAST DEVELOPMENT
Male breast development occurs in an analogous fashion to female breast development. At puberty in the female breast, complex hormonal interplay occurs resulting in growth and maturation of the adult female breast.
In early fetal life, epithelial cells, derived from the epidermis of the area programmed to later become the areola, proliferate into ducts, which connect to the nipple at the skin's surface. The blind ends of these ducts bud to form alveolar structures in later gestation. With the decline in fetal prolactin, placental estrogen and progesterone at birth, the infantile breast regresses until puberty.

During thelarche, the initial clinical appearance of the breast bud, growth and division of the ducts occur, eventually giving rise to club-shaped terminal end buds, which then form alveolar buds. Approximately a dozen alveolar buds will cluster around a terminal duct, forming the type 1 lobule. Eventually, the type 1 lobule will mature into types 2 and 3 lobules, called ductules, by increasing its number of alveolar buds to as many as 50 in type 2 and 80 in type 3 lobules. The entire differentiation process takes years after the onset of puberty and, if pregnancy is not achieved, may never be completed.

HORMONAL REGULATION OF BREAST DEVELOPMENT
The initiation and progression of breast development involves a coordinated effort of pituitary and ovarian hormones, as well as local mediators (see Figure 1).



Figure 1. Hormones affecting growth and differentiation of breast tissue. (GH= Growth Hormone; ER= Estrogen Receptor; PR= Progesterone Receptor; AR= Androgen Receptor)
Attached Thumbnails
*
ESTROGEN, GH AND IGF-1, PROGESTERONE, & PROLACTIN

Estrogen and progesterone act in an integrative fashion to stimulate normal adult female breast development. Estrogen, acting through its ER a receptor, promotes duct growth, while progesterone, also acting through its receptor (PR), supports alveolar development. This is demonstrated by experiments in ER a knockout mice which display grossly impaired ductal development, whereas the PR knockout mice possess significant ductal development, but lack alveolar differentiation.

Although estrogens and progestogens are vital to mammary growth, they are ineffective in the absence of anterior pituitary hormones. Thus, neither estrogen alone nor estrogen plus progesterone can sustain breast development without other mediators, such as GH and IGF-1, as confirmed by studies involving the administration of estrogen and GH to hypophysectomized and oophorectomized female rats, which resulted in breast ductal development. The GH effects on ductal growth are mediated through stimulation of IGF-1. This is demonstrated by studies of estrogen and GH administration to IGF-1 knockout rats that showed significantly decreased mammary development when compared to age-matched IGF-1- intact controls. Combined estrogen and IGF-1 treatment in these IGF-1 knockout rats restored mammary growth. In addition, Walden et al. demonstrated that GH-stimulated production of IGF-1 mRNA in the mammary gland itself, suggesting that IGF-1 production in the stromal compartment of the mammary gland acts locally to promote breast development. Furthermore, other data indicates that estrogen promotes GH secretion and increased GH levels, stimulating the production of IGF-1, which synergizes with estrogen to induce ductal development.
Like estrogen, progesterone has minimal effects in breast development without concomitant anterior pituitary hormones; again indicating that progesterone interacts closely with pituitary hormones. For example, prolonged treatment of dogs with progestogens such as ***ot medroxyprogesterone acetate or with proligestone caused increased GH and IGF-1 levels, suggesting that progesterone may also have an effect on GH secretion. In addition, clinical studies have correlated maximal cell proliferation to specific phases in the female menstrual cycle. For example, maximal proliferation occurs not during the follicular phase when estrogens reach peak levels and progesterone is low (less than 1 ng/mL [3.1nmol}), but rather, it occurs during the luteal phase when progesterone reaches levels of 10-20 ng/mL (31- 62nmol) and estrogen levels are two to three times lower than in the follicular phase. Furthermore, immunohistochemical studies of ER and PR showed that the highest percentage of proliferating cells, found almost exclusively in the type 1 lobules, contained the highest percentage of ER and PR positive cells. Similarly, there is immunocytological presence of ER, PR, and androgen receptors (AR) in gynecomastia and male breast carcinoma. ER, PR and AR expression was observed in 100% (30/30) of gynecomastia cases. Given these data and the fact that PR knockout mice lack alveolar development in breast tissue, it appears as if progesterone, analogous to estrogen, may increase GH secretion and act through its receptor on mammary tissue to enhance breast development, specifically alveolar differentiation (28, 18).
Prolactin is another anterior pituitary hormone integral to breast development. Prolactin is not only secreted by the pituitary gland but may be produced in normal mammary tissue epithelial cells and breast tumors. . Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone.




ANDROGEN AND AROMATASE

Estrogen effects on the breast may be the result of either circulating estradiol levels or locally produced estrogens. Aromatase P450 catalyzes the conversion of the C19 steroids, androstenedione, testosterone, and 16-a-hydroxyandrostenedione to estrone, estradiol-17b and estriol. As such, an overabundance of substrate or an increase in enzyme activity can increase estrogen concentrations and thus initiate the cascade to breast development in females and males. For example, in the more complete forms of androgen insensitivity syndromes in genetically male (XY) patients, excess androgen aromatizes into estrogen resulting in not only gynecomastia, but also a phenotypic female appearance. Furthermore, the biologic effects of over expression of the aromatase enzyme in female and male mice transgenic for the aromatase gene result in increased breast proliferation. In female transgenetics, over expression of aromatase promotes the induction of hyperplastic and dysplastic changes in breast tissue. Over expression of aromatase in male transgenics caused increased mammary growth and histological changes similar to gynecomastia, an increase in estrogen and progesterone receptors and an increase in downstream growth factors such as TGF-beta and bFGF. Interestingly, treatment with an aromatase inhibitor leads to involution of the mammalian gland phenotype. Thus, although androgens do not stimulate breast development directly, they may do so if they aromatize to estrogen. This occurs in cases of androgen excess or in patients with increased aromatase activity.



PHYSIOLOGIC GYNECOMASTIA

Gynecomastia, breast development in males, can occur normally during three phases of life. The first occurs shortly after birth in both males and females. This is caused by the high levels of estradiol and progesterone produced by the mother during pregnancy, which stimulates newborn breast tissue. It can persist for several weeks after birth and can cause mild breast discharge called "witch's milk".

Puberty marks the second situation in which gynecomastia can occur physiologically. In fact, up to 60% of boys have detectable gynecomastia by age 14. Although it is mostly bilateral, it can occur unilaterally, and usually resolves within 3 years of onset.

Interestingly, in early puberty, the pituitary gland releases gonadotropins in order to stimulate testicular production of testosterone mostly at nighttime. Estrogens, however, rise throughout the entire day. Some studies have shown that a decreased androgen to estrogen ratio exists in boys with pubertal gynecomastia when compared with boys who do not develop gynecomastia. Furthermore, another study showed increased aromatase activity in the skin fibroblasts of boys with gynecomastia. Thus, the mechanism by which pubertal gynecomastia occurs may be due to either decreased production of androgens or increased aromatization of circulating androgens, thus increasing the estrogen to androgen ratio.

The third age range in which gynecomastia is frequently seen is during older age (>60 years). Although the exact mechanisms by which this can occur have not been fully elucidated, evidence suggests that it may result from increased peripheral aromatase activity secondary to the increase in total body fat, coupled with mild hypogonadism associated with aging. For instance, investigators have shown increased urinary estrogen levels in obese individuals, and have demonstrated aromatase expression in adipose tissue. Thus, like the gynecomastia of obesity, the gynecomastia of aging may partly result from increased aromatase activity, causing increased circulating estrogen levels. Moreover, not only does total body fat increase with age, but there may be an increase in aromatase activity in the adipose tissue already present, increasing circulating estrogens even further. Lastly, SHBG increases with age in men. Since SHBG binds estrogen with less affinity than testosterone, the bioavailable estradiol to bioavailable testosterone ratio may increase in the obese older male.



PATHOLOGIC GYNECOMASTIA:

INCREASED ESTROGEN

Since the development of breast tissue in males occurs in an analogous manner to that in females, the same hormones that affect female breast tissue can cause gynecomastia. The testes secrete only 6-10 mg of estradiol and 2.5 mg of estrone per day. Since this only comprises a small fraction of estrogens in circulation (i.e. 15% of estradiol and 5% of estrone), the remainder of estrogen in males is derived from the extraglandular aromatization of testosterone and androstenedione to estradiol and estrone, respectively. Thus, any cause of estrogen excess from overproduction to peripheral aromatization of androgens can initiate the cascade to breast development.





TUMORS

Testicular tumors can lead to increased blood estrogen levels by: estrogen overproduction; androgen overproduction with aromatization in the periphery to estrogens; and by ectopic secretion of gonadotropins which stimulate otherwise normal Leydig cells. Tumors causing an overproduction of estrogen represent an unusual but important cause of estrogen excess.

Examples of estrogen-secreting tumors include: Leydig cell tumors, Sertoli cell tumors, granulosa cell tumors and adrenal tumors.
Interstitial cell tumors, or Leydig cell tumors constitute 1%-3% of all testis tumors.

Usually, they occur in men between the ages of 20 and 60, although up to 25% of them occur prepubertally. In prepubertal cases, isosexual precocity, rapid somatic growth, and increased bone age with elevated serum testosterone and urinary 17-ketosteroid levels are the presenting features.

In adults, elevated estrogen levels coupled with a palpable testicular mass and gynecomastia may develop. Though mostly benign, Leydig cell tumors may be malignant and metastasize to lung, liver, and retroperitoneal lymph nodes.

Sertoli cell tumors comprise less than 1% of all testicular tumors and occur at all ages, but one third have occurred in patients less than 13 years, usually in boys under 6 months of age. Although they arise in young boys, they usually do not produce endocrinologic effects in children. Again, the majority is benign, but up to 10% is malignant. Gynecomastia occurs in one third of cases, presumably due to increased estrogen production.

Granulosa cell tumors, which occur very rarely in the testes, can also overproduce estrogen. In fact, only eleven cases have been reported with gynecomastia as a presenting feature in half of them.

Germ cell tumors are the most common cancer in males between the ages of 15 and 35. They are divided into seminomatous and nonseminomatous subtypes and include embryonal carcinoma, yolk sac carcinoma, choriocarcinoma and teratomas. Elevated a fetoprotein (AFP) and b HCG function as reliable markers in some tumors. As a result of the increased b HCG, acting analogously to LH to stimulate the Leydig cell LH receptor, testicular estrogen production is also increased, which, in turn, can cause gynecomastia. Although germ cell tumors generally arise in the testes, they can also originate extra-gonadally, specifically in the mediastinum. These extragonadal tumors also possess the capability of producing b HCG, but they must be differentiated from a multitude of other tumors such as large cell carcinomas of the lung which can synthesize ectopic b HCG.

Some neoplasms that overproduce estrogens also possess aromatase overactivity. Sertoli Cell tumors in boys with Peutz-Jegher syndrome, an autosomal dominant disease characterized by pigmented macules on the lips, gastrointestinal polyposis and hormonally active tumors in males and females, for instance, have repeatedly demonstrated aromatase overactivity, resulting in gynecomastia, rapid growth and advanced bone age as presenting features. Feminizing Sertoli cell tumors with increased aromatase activity can also be seen in the Carney complex, an autosomal dominant disease characterized by cardiac myxomas, cutaneous pigmentation, adrenal nodules and hypercortisolism. Other than sex-cord tumors, fibrolamellar hepatocellular carcinoma has also been shown to possess ectopic aromatase activity, causing severe gynecomastia in a 17-year-old boy. Furthermore, adrenal tumors can secrete excess dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione that can then be aromatized peripherally to estradiol.






NON-TUMOR CAUSES OF ESTROGEN EXCESS:

INCREASED AROMATASE ACTIVITY
Besides tumors, other conditions have been associated with excessive aromatization of testosterone and androgens to estrogen, which results in gynecomastia. For instance, a familial form of gynecomastia has been discovered, in which affected family members have an elevation of extragonadal aromatase activity. More recently, novel gain-of-function mutations in chromosome 15 have been reported to cause gynecomastia, possibly by forming cryptic promoters that lead to over expression of aromatase. As stated, obesity may cause estrogen excess through increased aromatase activity in adipose tissue. Furthermore, hyperthyroidism induces gynecomastia through several mechanisms, including increased aromatase activity.


DISPLACEMENT OF ESTROGENS FROM SHBG
Another cause of gynecomastia from estrogen excess includes steroid displacement from sex-hormone binding globulin (SHBG). SHBG binds androgens more avidly than estrogen. Thus, any condition or drug that can displace steroids from SHBG, will more easily displace estrogen, allowing for higher circulating levels of estrogen. Drugs can cause gynecomastia by numerous mechanisms besides displacement from SHBG.

DECREASED TESTOSTERONE AND ANDROGEN RESISTANCE
Breast development requires the presence of estrogen. Androgens, on the other hand oppose the estrogenic effects. Thus, equilibrium exists between estrogen and androgens in the adult male to prevent growth of breast tissue, whereby either an increase in estrogen or a decrease in androgen can tip the balance toward gynecomastia. Increased estrogen levels will increase glandular proliferation by several mechanisms. These include direct stimulation of glandular tissue and by suppressing LH, therefore decreasing testosterone secretion by the testes and exaggerating the already high estrogen to androgen ratio.

Besides increased estrogen production, decreased testosterone levels can cause an elevation in the estrogen to androgen ratio, producing gynecomastia. Primary hypogonadism, with its reduction in serum testosterone and increased serum LH levels increases testicular estradiol production and is associated with an increased estrogen to androgen ratio. Klinefelter's syndrome, occurring in 1 in 500 males who possess an XXY karyotype and primary testicular failure, features gynecomastia as well, again presumably secondary to decreased testosterone production, compensatory increased LH secretion, overstimulation of the Leydig cells and relative estrogen excess. In addition, any acquired testicular disease resulting in primary hypogonadism such as viral and bacterial orchitis, trauma, or radiation can also promote gynecomastia by the same mechanisms.

Lastly, enzyme deficiencies in the testosterone synthesis pathway from cholesterol also result in ***ressed testosterone levels and hence a relative increase in estrogen. Deficiency of 17-oxosteroid reductase, the enzyme that catalyzes the conversion of androstenedione to testosterone and estrone and estrone to estradiol, for example, will cause elevation in estrone and androstenedione, which is then further aromatized to estradiol.

Secondary hypogonadism, if severe enough, results in low serum testosterone and unopposed estrogen effect from increased conversion of adrenal precursors to estrogens. Thus, patients with Kallmann's syndrome, a form of congenital secondary hypogonadism with anosmia, also develop gynecomastia. In fact, hypogonadism from whatever cause constitutes most cases of gynecomastia.

The androgen resistance syndromes, including complete and partial testicular feminization (e.g. Reifenstein's syndrome) are characterized by gynecomastia and varying degrees of pseudohermaphroditism. Kennedy Syndrome, a neurodegenerative disease, is also associated with decreased effective testosterone due to a defective androgen receptor. The gynecomastia is the combined result of decreased androgen responsiveness at the breast level and increased estrogen levels as a result of elevated androgen precursors of estradiol and estrone. As such, androgens in these diseases are not recognized by the peripheral tissues including the breast and pituitary. Androgen resistance at the pituitary results in elevated serum LH levels and increased circulating testosterone. The increased serum testosterone is then aromatized peripherally, promoting gynecomastia. Thus, gynecomastia is the result of increased estradiol levels that arise due to unopposed androgen unresponsiveness.

OTHER DISEASES
Other disease states have also resulted in gynecomastia.
Men with end stage renal disease may have reduced testosterone, and elevated gonadotropins. This apparent primary testicular failure may then lead to increased breast development.

The gynecomastia of liver disease, particularly cirrhosis, does not have a clear etiology. Some have speculated that the gynecomastia is the result of estrogen overproduction, possibly secondary to increased extraglandular aromatization of androstenedione, which may have decreased hepatic clearance in cirrhotics. However, testosterone administration to cirrhotics causes a rise in estradiol, but decreases the prevalence of gynecomastia. Therefore, although the association of gynecomastia with liver disease is apparent, current data are conflicting and the mechanism by which this occurs remains unclear.

As previously stated, thyrotoxicosis is associated with gynecomastia. Patients often have elevated estrogen that may result from a stimulatory effect of thyroid hormone on peripheral aromatase. Testosterone may also be increased possibly due to thyroid-hormone-stimulated increase in SHBG, as free testosterone is usually normal. Since SHBG binds testosterone more avidly than estradiol, there is a higher ratio of free estradiol to free testosterone. Thus, with normal testosterone and increased estrogen, there is an elevated estrogen to testosterone ratio. In addition, LH is also increased, which may also stimulate testicular estrogen synthesis.

Gynecomastia can also follow spinal cord disorders. Most patients with spinal cord disorders display ***ressed testosterone levels and, in fact, can develop testicular atrophy with resultant hypogonadism and infertility. Some have speculated that this may result from recurrent urinary tract infections, increased scrotal temperature, and a neuropathic bladder, which ultimately cause acquired primary testicular failure. The exact mechanism, however, remains elusive.

Refeeding gynecomastia refers to breast development in men recovering from a malnourished state. Although most cases regress within seven months, the etiology of this phenomenon has not been fully elucidated.
HIV patients can also develop gynecomastia. There is a high incidence of androgen deficiency due to multifactorial causes, including primary and secondary hypogonadism.




DRUGS
A significant percentage of gynecomastia is caused by medications or exogenous chemicals that result in increased estrogen effect. This may occur by several mechanisms: 1) they possess intrinsic estrogen-like properties, 2) they increase endogenous estrogen production, or 3) they supply an excess of an estrogen precursor (e.g. testosterone or androstenedione) which can be aromatized to estrogen.

Contact with estrogen vaginal creams, for instance, can elevate circulating estrogen levels. These may or may not be detected by standard estrogenic qualitative assays. An estrogen-containing embalming cream has been reported to cause gynecomastia in morticians.

Recreational use of *********, a phytoestrogen, has also been associated with gynecomastia. It has been suggested that digitalis causes gynecomastia due to its ability to bind to estrogen receptors.

The appearance of gynecomastia has been described in body builders and athletes after the administration of aromatizable androgens. The gynecomastia was presumably caused by an excess of circulating estrogens due to the conversion of androgens to estrogen by peripheral aromatase enzymes.

Drugs and chemicals that cause decreased testosterone levels either by causing direct testicular damage, by blocking testosterone synthesis, or by blocking androgen action can produce gynecomastia. For instance, phenothrin, a chemical component in delousing agents, possessing antiandrogenic activity, has been attributed as the cause of an epidemic of gynaecomastia among Haitian refugees in US detention centers in 1981 and 1982.

Chemotherapeutic drugs, such as alkylating agents, cause Leydig cell and germ cell damage, resulting in primary hypogonadism. Flutamide, an anti-androgen used as treatment for prostate cancer, blocks androgen action in peripheral tissues, while cimetidine blocks androgen receptors. Ketoconazole, on the other hand, can inhibit steroidogenic enzymes required for testosterone synthesis. Spironolactone causes gynecomastia by several mechanisms. Like ketoconazole, it can block androgen production by inhibiting enzymes in the testosterone synthetic pathway (i.e. 17a hydroxylase and 17-20-desmolase), but it can also block receptor-binding of testosterone and dihydrotestosterone.

In addition to decreasing testosterone levels and biologic effects, spironolactone also displaces estradiol from SHBG, increasing free estrogen levels.

Ethanol (For you Noobs: the alcohol consumed in beverages )increases the estrogen to androgen ratio and induces gynecomastia by multiple mechanisms as well. Firstly, it is associated with increased SHBG, which decreases free testosterone levels. Secondly, it increases hepatic clearance of testosterone, and thirdly, it has a direct toxic effect on the testes themselves. Unfortunately, besides the drugs stated, a multitude of others cause gynecomastia by unknown mechanisms.

Drugs that induce gynecomastia by known mechanisms:

Estrogen-like, or binds to estrogen receptor:

Estrogen vaginal cream
Estrogen-containing embalming cream
Delousing powder
Digitalis
Clomiphene (Clomid bros...Clomid )
*********

Stimulate estrogen synthesis:

Gonadotropins
Growth Hormone (Dammit... )

Supply aromatizable estrogen precursors:

Exogenous androgen (This should read aromatisable exogenous androgens ~Nark)
Androgen precursors (ie androstenedione and DHEA)

Direct Testicular Damage:

Busulfan
Nitrosurea
Vincristine
Ethanol (Yes you boozers.. the alchy DOES DAMAGE!)

Block testosterone synthesis:

Ketoconazole
Spironolactone
Metronidazole
Etomidate

Block androgen action:

Flutamide
Bicalutamide
Finasteride (yup...)
Cyproterone
Zanoterone
Cimetidine
Ranitidine
Spironolactone (repeat offender)

Displace estrogen from SHBG:

Spironolactone (repeat offender)
Ethanol (the booze does it again )




Drugs that cause gynecomastia by uncertain mechanisms:

Cardiac and antihypertensive medications:
• Calcium channel blockers (verapamil, nifedipine, diltiazem)
• ACE Inhibitors (captopril, enalapril
• b blockers
• Amiodarone
• Methyldopa
• Reserpine
• Nitrates
Psychoactive drugs:
• Neuroleptics
• Diazepam
• Neuroleptics
• Diazepam
• Phenytoin
• Tricyclic anti***ressants
• Haloperidol
Drugs for infectious diseases:
• Indinavir
• Isoniazid
• Ethionamide
• Griseofulvin
Drugs of Abuse:
• amphetamines
Other:
• Theophylline
• Omeprazole
• Auranofin
• Diethylpropion
• Domperidone
• Penicillamine
• Sulindac
• Heparin



MALE BREAST CANCER
Male breast cancer is rare and comprises only 0.2 percent of all male cancers. Although uncommon, it has been associated with gynecomastia and necessitates inclusion in the differential diagnosis. Other risks include Klinefelter's syndrome, exogenous estrogen exposure, family history, and testicular disorders. It is unclear if these are specific risks for breast cancer are linked to the stimulatory process responsible for gynecomastia. New evidence suggests obesity and consumption of red meat may also raise the risk for the development of male breast cancer.

PATIENT EVALUATION:

HISTORY AND PHYSICAL EXAMINATION
At presentation, all patients require a thorough history and physical exam. Particular attention should be given to medications, drug and alcohol abuse, as well as other chemical exposures. Symptoms of underlying systemic illness, such as hyperthyroidism, liver disease, or renal failure should be sought. Furthermore, the clinician must recall neoplasm as a possible etiology and should establish the duration and timing of breast development. Obviously, rapid breast growth that has occurred recently is more concerning than chronic gynecomastia.

Additionally, the clinician should inquire about fertility, erectile dysfunction and libido to rule out hypogonadism, either primary or secondary, as a potential cause.

In our experience, the breast examination is best performed with the patient supine and with the examiner palpating from the periphery to the areola. The glandular mass should be measured in diameter. Gynecomastia is diagnosed by finding subareolar breast tissue of 2 cm in diameter or greater. Malignancy is suspected if an immobile firm mass is found on physical examination. Skin dimpling, nipple retraction or discharge, and axillary lymphadenopathy further support malignancy as a possible diagnosis.

A thorough testicular exam is essential. Bilaterally small testes imply testicular failure, while asymmetric testes or a testicular mass suggest the possibility of neoplasm. Visual field impairment may suggest pituitary disease. Physical findings of underlying systemic conditions such as thyrotoxicosis, HIV disease, liver, or kidney failure should also be assessed.





LABORATORY EVALUATION
All patients who present with gynecomastia should have serum testosterone, estradiol, LH and b HCG measured. Further testing should be tailored according to the history, physical examination and the results of these initial tests. An elevated b HCG or a markedly elevated serum estradiol suggests neoplasm and a testicular ultrasound is warranted to identify a testicular tumor, keeping in mind, however, that other non-testicular tumors can also secrete b HCG. A low testosterone level, with an elevated LH and normal to high estrogen level indicates primary hypogonadism. If the history suggests Klinefelter's Syndrome, then a karyotype should be performed for definitive diagnosis. Low testosterone, low LH and normal estradiol levels imply secondary hypogonadism, and hypothalamic or pituitary causes should be sought. If testosterone, LH and estradiol levels are all elevated, then the diagnosis of androgen resistance should be entertained. Liver, kidney and thyroid function should be assessed if the physical examination suggests liver failure, kidney failure, or hyperthyroidism, respectively. Furthermore, if examination of breast tissue suggests malignancy, a biopsy should be performed. This is of particular importance in patients with Klinefelter's syndrome, who have an increased risk of breast cancer.



TREATMENT
Treatment of the underlying endocrinologic or systemic disease that has caused gynecomastia is mandatory. Testicular tumors, such as Leydig cell, Sertoli cell or granulosa cell tumors should be surgically removed. In addition to surgery, germ cell tumors are further managed with chemotherapy involving cisplatin, bleomycin and either vinblastine or etoposide.

Should underlying thyrotoxicosis, renal or hepatic failure be discovered, appropriate therapy should be initiated. Medications that cause gynecomastia should also be discontinued whenever possible based on their role in management of the underlying condition. Of course, if a breast biopsy indicates malignancy, then mastectomy should be performed.
If no pathologic abnormality is detected, then appropriate treatment is close observation. A careful breast exam should be done initially every 3 months until the gynecomastia regresses or stabilizes, after which a breast exam can be performed yearly. It is important to remember that some cases of gynecomastia, especially that which occurs in pubertal boys, can resolve spontaneously. (Mine didn't )





MEDICAL TREATMENT
If the gynecomastia is severe, does not resolve, and does not have a treatable underlying cause, some medical therapies may be attempted.

There are 3 classes of medical treatment for gynecomastia: androgens (testosterone, dihydrotestosterone, danazol), anti-estrogens (clomiphene citrate, tamoxifen) and aromatase inhibitors such as testolactone.

Testosterone treatment of hypogonadal men with gynecomastia often fails to produce breast regression once gynecomastia is established. Unfortunately, testosterone treatment may actually produce the side effect of gynecomastia by being aromatized to estradiol. Thus, although testosterone is used to treat hypogonadism, its use to specifically counteract gynecomastia is limited.

Dihydrotestosterone, a non-aromatizable androgen, has been used in patients with prolonged pubertal gynecomastia with good response rates. Since dihydrotestosterone is given either intramuscularly or percutaneously, this may restrict its usefulness.

Danazol, a weak androgen that inhibits gonadotropin secretion, resulting in decreased serum testosterone levels, has been studied in a prospective placebo-controlled trial, whereby gynecomastia resolved in 23 percent of the patients, as opposed to 12 percent of the patients on placebo. Unfortunately, undesirable side effects including edema, acne, and cramps have limited its use.

Investigators have reported a 64 percent response rate with 100 mg/day of clomiphene citrate, a weak estrogen and moderate antiestrogen. Lower doses of clomiphene have shown varied results, indicating that higher doses may need to be administered, if clomiphene is to be attempted.

Tamoxifen, also an antiestrogen, has been studied in 2 randomized, double-blind studies in which a statistically significant regression in breast size was achieved, although complete regression was not documented.

One study compared tamoxifen with danazol in the treatment of gynecomastia. Although patients taking tamoxifen had a greater response with complete resolution in 78 percent of patients treated with tamoxifen, as compared to only a 40 percent response in the danazol-treated group, the relapse rate was higher for the tamoxifen group.

Although complete breast regression may not be achieved and a chance of recurrence exists with therapy, tamoxifen, due to relatively lower side effect profile, may be a more reasonable choice when compared to the other therapies. If used, tamoxifen should be given at a dose of 10 mg twice a day for at least 3 months.

An aromatase inhibitor, testolactone, has also been studied in an uncontrolled trial with promising effects. Further studies must be performed on this drug before any recommendations can be established on its usefulness in the treatment of gynecomastia.

Newer aromatase inhibitors such as anastrozole and letrozole may have therapeutic potential but no study has been published to confirm its efficacy in treatment of gynecomastia.



SURGICAL TREATMENT
When medical therapy is ineffective, particularly in cases of longstanding gynecomastia, or when the gynecomastia interferes with the patient's activities of daily living, or when there is suspicion of malignancy of breast, then surgical therapy is appropriate. This includes removal of glandular tissue coupled with liposuction, if needed. In our experience, uses of delicate cosmetic surgical techniques are warranted to prevent unsightly scarring.


PREVENTION OF GYNECOMASTIA IN MEN WITH PROSTATE CANCER
Because androgen ***rivation is one of the commonly used treatment modalities for advanced prostate cancer, its possible role in the development of gynecomastia is of particular concern to clinicians. Low dose prophylactic irradiation has been variably reported to reduce the rate of gynecomastia in men receiving estrogens or antiandrogens for advanced prostate cancer
.
SUMMARY
In summary, gynecomastia is a relatively common disorder. The causes of its development range vastly from benign physiologic processes to rare neoplasms. Thus, in order to properly diagnose the etiology of the gynecomastia, the clinician must understand the hormonal factors involved in breast development. Parallel to female breast development, estrogen, along with GH and IGF-1 is required for breast growth in males. Since a balance exists between estrogen and androgens in males, any disease state or medication that can increase circulating estrogen or decrease circulating androgen, causing an elevation in the estrogen to androgen ratio, can induce gynecomastia.

Due to the diversity of possibly etiologies, including neoplasm, performing a careful history and physical is imperative. Once gynecomastia has been diagnosed, treatment of the underlying cause is warranted. If no underlying cause is discovered, then close observation is appropriate. If the gynecomastia is severe, however, medical therapy can be attempted and if ineffective, glandular tissue can be removed surgically.[/b]
__________________

Yohimbe wrote:

milktuds wrote:

Prop(8 weeks), Var(5 weeks), Masteron(6 weeks)

Have you stopped the masteron already? If so, why did you only run the masteron for 6 weeks but the cycle was 8 weeks-was it masteron prop, not an enanthate ester?

Masteron will act as an anti E and limit the estrogen effects from testosterone aromatisation, so I would have used it right through the cycle.

Right now I'd use the nolva to block the receptors to stop the estrogen being soaked up by the body. If you were using masteron prop, start using it again until the cycle has finished.

Then start letrozole anti gyno protocol if it is still there.

I have a thread on gyno reversal I'll post

Masteron was a mix of a Prop(50mg) and Enanthate(100mg) ester. I think maybe the Masteron caused an estrogen rebound effect???

I am using Nolva along with Letro. I was thinking of doing this. I will use Nolva for about 2 weeks along with the Letro, then drop the Nolva and continue with letro until the gyno is reversed. I hope.

OK seeing that my cycle ends next week Wed and PCT starts 5 days after that. Do I just run the gyno reversal protocol and then do a PCT?

milktuds wrote:

Masteron was a mix of a Prop(50mg) and Enanthate(100mg) ester. I think maybe the Masteron caused an estrogen rebound effect???

I am using Nolva along with Letro. I was thinking of doing this. I will use Nolva for about 2 weeks along with the Letro, then drop the Nolva and continue with letro until the gyno is reversed. I hope.

OK seeing that my cycle ends next week Wed and PCT starts 5 days after that. Do I just run the gyno reversal protocol and then do a PCT?

What dose of masteron were you on?

With a enth ester there should still be a fair amount in your blood if you've only been off for less than a week.
I don't think it's the masteron, it should still be a quite high blood levels.

Start the nolva to block the receptors if you haven't already. And then start the gyno reversal. How bad is the gyno? Gyno is usually a hard lump behind the nipple.

Then start the letro protocol. I'd overlap the nolva and letro by about a week so the letro has definitely taken effect before you stop the nolva, but this will reduce the letro absorption by 37%.

I think I'd lower the test dose but extend the cycle until you have finished the letro gyno protocol. Then start pct.

Then start the nolva a few days before you finish the letro gyno reversal and run for a few weeks so you don't get estrogen rebound. This will be your pct if you extend the test prop until the end of the gyno reversal period.


Some may differ, but IMO letro gyno reversal is harsh on your body and the increased androgens will help you cope. You'll be shutting down virtually all estrogen conversion from testosterone anyway on this dose

Masteron 150mg EOD
I started Nolva and Letro as soon as I noticed the puffy nipples.

I think it's fatty deposits forming under the nipple. No hard lump.

Gonna post pics.

Fuck, pics won't upload.

Go with the letro protocol-it's cause will be estrogen related regardless and need to nip in the bud-no pun-before it gets out of hand

What doages are you following at the moment? And what doses of test?

Test Prop 200mg EOD
Letro 2.5mg/day
Kessar 20mg/day

Maybe finish out your intended 8 weeks and then drop the test to 100mg EOD for the duration of the letro gyno protocol, hopefully that should take care of the problem and then start pct once the gyno has subsided

I'm in agreement with running the tamoxifen with the letro, then running the letro.

However I would integrate the PCT into the gyno removal protocol. Once you are sure the letro has kicked in, start the HCG. Since aromatase is blocked you wont aggravate the gyno with the HCG, but you will kick the testes into test production...

Then after running the HCG for two weeks or however long you plan contiune with the letro (if you still need it because gyno is not completely gone) and follow with tamoxifen as suggested above.

The letro and SERM following the HCG will maintain signals to the brain to keep producing test wile simultaneously fighting the gyno.

If you chose to only do PCT after gyno reversal you face the risk of reintroducing the gyno when estrogen levels spike following HCG usage.

OK I have got enough juice left to pin until the 17/11/2009. I will run Letro and Kessar until 25/11/2009. Then drop the Kessar. Continue with Letro. 02/12/2009 Start HCG and run for 3 weeks. After HCG start Kessar again. Still Running Letro. A week before Kessar is finished taper Letro off.

I think that sounds good.
You only need to run the letro at those doses until the gyno is gone. Running letro at those doses is harsh on your body, it will affect your immune system, libido and joints. Don't run it for longer than you need to.

My logic on running the test through the letro gyno removal period is that the letro will already be hammering your body. During pct, no matter how good it is, there will always be a period where your androgen levels are down and cortisol is up.
This added to the hammering from the letro and you may get sick from weakened immunity. The letro is already stopping 98% of estrogen aromatase, so the high testosterone should not have an impact on the effectiveness of the letro gyno reversal.

At least if you still have high androgens, this should reduce cortisol levels and hopefully offset the hammering you are taking from the letro.

BTW I've never done this so don't know how harsh it is personally, just going off other guys saying that it really hammers you.

I think I have found my problem. In week three I started HCG at 375IU E3D to maintain my balls. Maybe this caused all the estrogen?

Maybe not.

Possible-I don't think it's solely responsible, but maybe the combination of testosterone and HCG may have elevated levels too high that the masteron wasn't enough to control it.

Either way, the letro is going to be your best bet at getting rid of it

If you have gyno I very much doubt thats going to work.... if you have gyno and you don't want it to stick around before surgery, I would leave the juice, do as Inja said, do your PCT, but i'm telling you HCG is going to F you up, its going to make it worse even with 2.5mg letro... but regardless you have to do it... I would make sure i'm doing 500iu shots instead of 1500iu for the HCG and rather do it slightly longer. you honestly need all the crap out your system for the letro to work and letro + nolva is not a good idea as it just cancels each other out... yes its required for the PCT so use it... clean your system out now from those longer esters and fix the gyno, no points having a good body with soft breast tissue and ugly nipples.

Pump what's your email again, something like hackcoza or something?
Would like you to take a look at my gyno and see how bad it is seeing that you have got some experience. I can't seem to upload any pics onto the forum.

EMAIL ADDRESS REMOVED

jeah, i'm really in two minds about gyno reversal with the use of letro or nolva or parlodel or anything in that matter... everyone writes huge articles but I never see people actually writing with success personally, everyone says, no use letro it will kill it, then i ask has it worked for you, hmm, ja a little bit... i'm like well has it really worked or is it in your head you think its working.... i can't find jack on google with enough people saying, hey, had gyno for some time and its 100% cured... you can find allot of the time gyno can get better on its own just by staying off anabolics for some time... so who is to say its not just your body sorting it out to a degree. anyway, i will continue to do research untill i have enough evidence to make a clear cut statment, and i will be making it based on my own body seeing this gyno is new and ive just had surgery... so if this doesn't work i honestly will stick to my guns and say you can't reverse gyno you need surgery.

OK, first things first...the thread title is meant to provoke some discussion. I'm not sold on the idea of "prolactin induced gyno" but I'd like to hear people's explanations of this and find out where they are getting their info from. And I realize that this should probably be in the science section, but I think a lot of people don't look there and more people here will hopefully get something out of this.

Statements about "prolactin induced gyno" often appear in discussions about "progestins" and "progesterone gyno." I feel that there is a lot of confusion about these two hormones and how they relate to gyno formation. I'd like to try to give my perspective on this and why I feel these are incorrect, or at least too simplistic explanations for the potential of a given compound to cause gyno symptoms.

I'm going to start with a discussion of progesterone and "progestins" and then talk a bit about prolactin. Hopefully all this will stimulate a good discussion. Like I said above, I'd like to hear where people are getting their info on "progestin gyno" and "prolactin gyno."


What does progesterone do?

In women, progesterone has multiple roles during pregnancy It causes changes in uterine tissue necessary for implantation and aids in the development of the breast ductal system in preparation for lactation.

Progesterone is a key precursor and steroidogenic intermediate for all bioactive natural steroids and the progesterone receptors A and B are structurally and evolutionarily the closest members of the nuclear receptor superfamily to the androgen receptor. Yet, although progesterone has crucial gestational and lactational roles in female reproductive physiology, it has no well established role in male reproductive physiology apart from a possible role in sperm function (234), possibly via non-genomic rather than a classically genomic mechanism (235). Nevertheless functional nuclear progesterone receptors are expressed in male brain, smooth muscle and reproductive, but not most non-reproductive tissues (236). Synthetic progestins, steroidal structural agonistic analogs of progesterone, are potent inhibitors of pituitary gonadotropin secretion used widely for female contraception and hormonal treatment of disorders such as endometriosis, uterine myoma and mastalgia. Used alone, progestins suppress spermatogenesis but cause androgen deficiency including impotence (237, 238) so androgen replacement is necessary. Non-human primate studies indicate that this is mediated via a central hypothalamic-pituitary site of action rather than direct effects on the testis (239).
endotext.com/male/male15/maleframe15.htm
Other effects we are interested in:

1) Antagonism of 5alpha-reductase. One theory is that progesterone competes with testosterone for binding to 5a-R. This would reduce the conversion of T to DHT and thus lower DHT levels. In males, this can be considered a "feminizing effect."

2) Elevates SHBG levels. SHBG binds to testosterone much better than to estrogen. Therefore, increased SHBG levels will decrease free test levels faster than free estrogen. This will create a transient imbalance in the free (active) T/E ratio. (On a side note, this difference in affinity for SHBG also means that estrogen can be released from SHBG "more easily" than test by supplements that are meant to interfere with test-SHBG interactions).

3) Can be converted to androstenedione, which can then be converted to estradiol. Increased levels of progesterone could lead to increased circulating estrogen.

4) In men, excess progesterone can rapidly shut down the HPTA.

5) Down-regulate or up-regulate ER expression? (Haven't found a clear answer to this yet, but it is an important question)


What is a progestin?

From my experience, on this and other boards you can find lots of references to such and such steroid/prosteroid/prohormone being a "progestin" and thus a string of warnings for people to watch out for gyno (which isn't a bad warning under any circumstances, really). However, many of these compounds, at least from what I can tell, are not, in fact progestins, at least in a strictly chemical sense. Here's Patrick Arnold talking about progestins:

most of these componunds people are calling progestins are not really progestins. they share vague chemical similarity with known pharmaceutical progestins and maybe have slight progestational activity but in my expert opinion would NOT fall into the category of progestin. they would be considered in the androgen class.

case in point would be estra-4,9-dien-3,17-dione

[a] "progestin is something that has progestational activity. but the complicated thing is most androgens have a certain degree of progestational activity (albeit minor for most)

its really a subjective call. certainly something like norethindrone from birth control pills can be considered a progestin (even though it has substantial androgenic activity). and then norethandrolone would be considered an androgen (even though it is very close in structure to norethindrone and has substantial progestational activity)

then there is the chemical aspect of what is a progestin

there are two classes of progestins - the C20-keto progestins such as classic progesterone and its derivatives, and the 17alpha-ethynyl estren derivatives such as norethindrone and norgestrel

i would think anything that is not in these structural classes would not be considered a progestin by an authority in this field. the only supplement i am aware of that fit this definition was the stuff that was in the old methyl-1-p (which was a C20-keto derivative)"

So as you can see, one problem is that while most of these compounds cannot be chemically classified as progestins, it is, as PA said, possible that some of them (or some of their metabolites) may have some level of activity at the progesterone receptor. I, for one, would like to see such info for many of these compounds, but I doubt that I could scour PubMed for the next year and be able to compile a halfway decent chart of "compounds and their metabolites that may or may not have progestational activity (that may or may not lead to gyno)."

I feel that for discussion's sake, when talking about compounds we should try to know whether they are progestins or androgens with some progestational activity. For example, nandrolone supposedly is able to activate the PR (progest. receptor) about 1/5th as well as progesterone itself, whereas trenbolone is closer equal activation. Neither of these compounds can be chemically classified as progestins, yet have substantial progestational activity.
Gynecomastia?

Almost 25% of all cases of gynaecomastia are currently classified as idiopathic. In this group of patients, circulating sex hormones, SHBG and gonadotrophins are within reference limits. The development of gynaecomastia is attributed to an altered tissue response which may be due to reduction in androgen receptors (75) and/or a local increase in aromatase activity in the breast.(46) Reduction in androgen receptors may be congenital or induced by drugs.

Ann Clin Biochem 2001; 38: 596-607

The effects of progesterone listed above, namely reduced levels of DHT and elevated SHBG may be integral to any role in gyno formation.

Here's another quote that I think is relevant (but I don't know the original source) talks about the contribution of DHT levels:

"In addition to elevated IGF-1, lowered DHT levels resulting from endogenous testosterone suppression may contribute to gyno from non aromatizing steroids. Gyno is a reported side effect from finasteride use. Some have attributed this to elevated estrogen levels due to the fact that there is more testosterone to be aromatized, since less test is being converted to DHT. Other researches think that DHT has a direct antiestrogenic effect on breast tissue.

Studies have shown that DHT can actually block estrogen from binding to the estrogen receptor in mammary tissue (1). DHT also is an aromatase inhibitor (2). Even more interesting is the fact that transdermal DHT cream has been used successfully to treat gyno (3).

It may be that the estrogen/DHT ratio is more important to the development of gyno than the estrogen/testosterone ratio."

So what may be happening is:

1) Progestin/progesterone ---> increased progesterone receptor signaling (which leads to) --> increased IGF-1 expression ----> stimulation of alveolar hyperplasia (not sure exactly how much this contributes to gyno)

2) Progestin/progesterone ---> increased progesterone receptor signaling--> lowered DHT levels ---> decreased antiestrogenic DHT activity in breast tissue = decreased DHT block of estrogen receptors in breast AND decreased DHT anti-aromatase activity in breast

The question that must be asked for each individual androgen is how much relative progestational activity does it have.

For example if nandrolone blocks DHT formation more so than trenbolone, but trenbolone elevates SHBG more than nandrolone, the relative importance of these effects will determine which compound is more likely to lead to gyno. By most accounts, nandrolone is more effective at this (especially when combined with test, which likely results in elevated estrogen at the same time), suggesting that the effects on DHT are more critical.


Prolactin

Where does prolactin come into this? Prolactin is a pituitary hormone that causes lactation. During pregnancy, it is the combined rise in estrogen and progesterone that contributes to prolactin production, i.e. progesterone causes development of the gland, and estrogen causes accumulation of prolactin that will eventually cause secretions (both of which probably depend on GH and IGF-1 signaling). In women, the drop in estrogen and progesterone after birth basically releases a hold on prolactin induced milk secretion. Here, estrogen and progesterone suppress lactation until after the baby is born; then levels of E and P drop off and prolactin takes over.


Is there a similar thing happening in men taking progestational androgens? In this case it might be that increased E and progestational signaling (if you're on a suppressive compound that also acts on the progesterone receptor) causes gyno formation (and increased prolactin levels), and then when you stop the compound and go into PCT (loss of E and progestational signaling), lactation is possible.

In men,

In general, an increase in effective oestrogen/androgen ratio, irrespective of the cause, may actually stimulate prolactin release and increase circulating concentrations.

Ann Clin Biochem 2001; 38: 596-607

and

www.endotext.org/male/male14/male14.htm

Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone.
and with regard to gyno:
Although prolactin receptors have been demonstrated in breast tissue, including gynecomastia [19], hyperprolactinemia probably plays an indirect role in gynecomastia by causing central hypogonadism. Most men with gynecomastia do not have elevated serum prolactin levels, and not all men with hyperprolactinemia develop gynecomastia. Nevertheless, it has been shown in cultured breast cancer cells that prolactin and sex steroid receptors (especially the progesterone receptor [PgR]) may be coexpressed and may cross-regulate each other?s expression [20,21]; acute prolactin treatment produced an increase in PgR and a decrease in AR content. If this were to occur in the breast tissue of hyperprolactinemic men, the resulting increase in PgR expression and decrease in AR expression could promote breast tissue growth and result in gynecomastia.

[19] Gill S, Peston D, Vonderhaar BK, et al. Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study. J Clin Pathol 2001;54:956?60.

[20] Ormandy CJ, Hall RE, Manning DL, et al. Coexpression and cross-regulation of the prolactin and sex steroid hormone receptors in breast cancer. J Clin Endocrinol Metab 1997;82(11): 3692?9.

[21] Gutzman JH, Miller KK, Schuler LA. Endogenous human prolactin and not exogenous human prolactin induces estrogen receptor a and prolactin receptor expression and increases estrogen responsiveness in breast cancer cells. J Steroid Biochem Mol Biol 2004;88:69?77.

from: Endocrinol Metab Clin N Am (2007) 36: 497?519


While prolactin and progestins on their own don't seem to cause gyno, is it possible that something similar to the post-pregnancy lactation in women could happen in men taking progestational androgens? In this case it might be that increased E and progestational signaling (if you're on a suppressive compound that also acts on the progesterone receptor) causes gyno formation (and increased prolactin levels), and then when you stop the compound and go into PCT (loss of E and progestational signaling), lactation is possible.

(continued below)
tilebreaker
06-22-2008, 01:54 PM
This is an important excerpt from an article by Karl Hoffman that I believe sums up a lot of the issues here:

PROGESTERONE AND PROLACTIN INDUCED GYNECOMASTIA

Before delving into this subject, I'd like to say first and foremost, that in users of anabolic/androgenic steroids (AAS) the first step in combating the development of gynecomastia, or male breast enlargement, is to eliminate the causative agent: the anabolic steroid. Drug-induced gynecomastia almost invariably resolves on its own when a person quits taking the drugs responsible for it, if caught before permanent fibrosis develops. Unfortunately, most AAS users don't want to employ this simple approach, for obvious reasons, so the foregoing will all be under the assumption that a person wants to prevent or treat gyno and still continue steroid use.

In the belief that certain anabolic steroids increase prolactin levels as well as act as agonists at the progesterone receptor, some have advocated the use of antiprolactin agents, like bromocriptine, or progesterone receptor blockers like RU-486 to treat AAS related gynecomastia, in lieu of more traditional drugs like tamoxifen.

In truth, the etiology of gynecomastia is unknown and a number of agents including estrogens, progestins, GH, IGF-1, and prolactin may be involved. However, most authorities believe that a decreased (T+DHT)/E ratio is central to the development of gyno, and that blocking the effects of estrogen, or increasing T + DHT levels, is central to ameliorating the problem.

Regarding prolactin, androgens decrease prolactin levels whereas estrogens increase prolactin. Non-aromatizing androgens have never been shown to elevate prolactin levels in humans, but testosterone has, due to its aromatization to estradiol (19). Prolactin secreting tumors, or prolactinomas, are often associated with gyno. But in these cases the prolactin is believed to induce gyno by suppressing testosterone production: "Prolactinomas that are sufficiently large to cause gynecomastia do so as a result of impairment of gonadotropin secretion and secondary hypogonadism" (20). However, this is a moot issue in AAS users whose gonadotropin secretion is already blunted.

According to research cited in (20), prolactin may have a direct stimulatory effect on mammary tissue development, but only in the presence of high estrogen levels.

The presence of mild hyperprolactinaemia is therefore not uncommon in patients with estrogen excess. Significant primary hyperprolactinaemia, on the other hand, may directly stimulate epithelial cell proliferation in an estrogen-primed breast, causing epithelial cell proliferation and gynaecomastia.

So rather than focusing solely on lowering prolactin levels which may be elevated in users of aromatizing androgens, attacking estrogen should be the first line of action.

GH and IGF-1 are considered critical to the proliferation of mammary tissue. An excellent review of the role played by these hormones, as well as a general overview of gynecomastia can be found here: [lost link; possibly www.endotext.org/male/male14/male14.htm

Since elevated GH and IGF-1 are considered important to the anabolic effect of AAS, it would be impractical and counterproductive to attempt to prevent gynecomastia by blocking GH/IGF.

Progesterone acts in concert with estrogen to promote breast development, and at least part of any role played by synthetic progestins may be to stimulate IGF-1 production in the breast. But again, blocking the action of progesterone or synthetic progestins is not practical. Specific progesterone receptor antagonists like RU-486 block not only the progesterone receptor, but the androgen receptor as well, and have actually been associated with the development of gynecomastia (21). In any case, progesterone is thought to act on the breast to enhance the effects of estrogen (22) so once again, attacking estrogen is the easiest and most logical approach.

DHT gel (Andractim) or a generic knockoff might help as well. DHT is thought to act as an aromatase inhibitor (23) and perhaps compete directly with estrogen for binding at the estrogen receptor (24). DHT has been used in several case reports and controlled trials to successfully treat gynecomastia. So perhaps a viable strategy would be to combine DHT gel with tamoxifen. I would recommend tamoxifen rather than an aromatase inhibitor due to the simple fact that tamoxifen has been widely used in numerous controlled studies to succesfully treat gynecomastia, whereas the evidence to support the efficacy of aromatase inhibitors is scanty at best.

(19) Nicoletti I, Filipponi P, Fedeli L, Ambrosi F, Gregorini G, Santeusanio F
Acta Endocrinol (Copenh) 1984 Feb;105(2):167-72

(20) Ismail AA, Barth JH.Ann Clin Biochem 2001 Nov;38(Pt 6):596-607

(21) Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russell CA, Lucci L, Stevenson LL J Neurosurg 1991 Jun;74(6):861-6

(22) Nomura K, Suzuki H, Saji M, Horiba N, Ujihara M, Tsushima T, Demura H, Shizume K
J Clin Endocrinol Metab 1988 Jan;66(1):230-2

(23) Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW
J Clin Endocrinol Metab 1984 Mar;58(3):467-72

(24) Casey RW, Wilson JD.
J Clin Invest 1984 Dec;74(6):2272-8

www.mindandmuscle.net/articles/karl_hoffman/myths


Conclusions:

It seems that all the problems that come with increased progestational activity may require high estrogen to become really noticable...so if you can stop the estrogen (on cycle or during the "rebound"), you should have a good chance of avoiding the progestational sides...that's my theory from my reading, anyway.

And finally, prolactin does NOT cause gyno (well, only in extremely rare cases) in most PH/DS/AAS users. It can cause lactation if gyno (generally caused by low T/E ratio, i.e. low T, high E; increased progestational activity is also involved) has progressed to the point where the ductal systems are more developed and prolactin levels have risen enough to trigger lactation. Increased prolactin and subsequent lactation is a side effect of gyno, not a cause.


More info on general male and female endocrinology:

endotext.com/male/index.htm

endotext.com/female/index.htm

Holy crap!!! :woohoo: ...........INJA!!!! :laugh:

The Rabbit wrote:

Holy crap!!! :woohoo: ...........INJA!!!! :laugh:

:huh: Why is my crap holy?

Mr. Pumper wrote:

A very long post

Hey bro, I've seen that post before somewhere? Where's it from?
All round good post yes, good read for anyone tackling gyno.

So are we still in agreement about fighting the gyno as part of PCT? Any modifications you think are necessary to what I suggested above?

Also in the thread you mention from personal experience that the HCG will aggravate the gyno. Was this in the presence of tamoxifen as I suggested above?

From forum.bodybuilding.com/archive/index.php/t-108715151.html

Well the bottom line is we need to PCT so that we can't stop. The effects of removing the gyno or shrinking it during PCT I doubt will work until you stop the HCG.

The HCG aggravating the gyno was in presence of 2.5mg letro p/d and had been running it for a few weeks prior to using the HCG so I did have a stable level present.

The other issue is that the Nolva will for sure lower plazma levels of the Letro so until you finish your PCT I doubt you will really have much effect at reverting it... I am doing a gyno removal cycle only now, letro at 1.25mg p/d and might bump it up, however I don't see much scientific evidence that anything above this dose will aid in any benefit. so until I find something medical to state otherwise i'll stick to that dose. what i am trying to determine is if it would be wise to stack Bromocriptine (Parlodel) or Dostinex (cabergoline) or will it actually be less effective.

what i have read is that the only time high prolactin levels become a problem is in the presence of high estrogen, so how in my case at 2.5mg of letro p/d would it aid in the development of gyno. i'm starting to think there is more to this puzzle.