Estrogen Will It Effect My Gains

[mr newbreed]

good post Merc...always comin through in the clutch.

I dont need any AI's during cycle - I may use nolva to keep bloat down but thats it...PCT i always used to use clomid and nolva but this time around I am going to use Aromasin and nolva.

yeah everything ive read off merc is really informative/helped me alot so far.
IN your opinion then would you only run an AI if gyno started,if i didnt just leave it alone

[Merc..]

so just to finalize,do you recomend running any AI even if there is no sign of gyno,or should it be used as and when needed?

If using tren I would consider using letro the entire cycle , from the start .... ( another benefit IMO is that letro has been shown to lower PgR )

Letro is strong and alot of people dont seem to like it ... Like I said I had to play with the dose ..


Merc.

[JasonR]

The solution ? SELECTIVE estrogen receptor modulator like torem, ralox or nolva, IMO should be introduced to ANY CYCLE, if not to combat breast tissue sides, then to maintain healthy cholesterol levels and well being.

[Merc..]

The solution ? SELECTIVE estrogen receptor modulator like torem, ralox or nolva, IMO should be introduced to ANY CYCLE, if not to combat breast tissue sides, then to maintain healthy cholesterol levels and well being.

Also keep in mind that nolva lowers Igf-1 which can reduce gains ....



Merc.

[JasonR]

Is it only nolva or all SERMS ?
I thought a SERM acts AS estrogen is most of the body unlike AI's ... where is the study saying it reduces IGF ?

[gman13]

very informative info! I dont think alot of people realize that the very same thing (estrogen) that can hurt you also helps you! You need estrogen to build muscle plain and simple...

[Merc..]

Is it only nolva or all SERMS ?
I thought a SERM acts AS estrogen is most of the body unlike AI's ... where is the study saying it reduces IGF ?

Here is one study on it.. There are alot of studies done on this..


Tamoxifen reduces serum insulin -like growth factor I (IGF-I).Pollak MN, Huynh HT, Lefebvre SP.
McGill University, Montreal, Quebec, Canada.

Antiestrogens are widely used in the management of hormonally responsive breast cancer in both adjuvant and palliative settings, and are currently being evaluated as chemopreventive agents. The classical mechanism of action of these drugs involves inhibition of estrogen-stimulated neoplastic cell proliferation by blockade of estrogen receptors present on breast cancer cells. This paper reviews recent clinical and laboratory data that suggest that the commonly used antiestrogen tamoxifen also acts to reduce serum IGF-I levels. Estrogens appear to play a permissive role in growth hormone (GH) release by the pituitary gland and GH is known to stimulate IGF-I expression by hepatocytes. It is therefore possible that blockade of estrogen receptors in the hypothalamic-pituitary axis by tamoxifen interferes with GH release, leading to reduced hepatic IGF-I expression. In view of results suggesting that IGF-I is a more potent mitogen than estradiol for breast cancer cells and data demonstrating a positive correlation between estrogen receptor level and IGF-I receptor level of breast cancer cells, the IGF-I lowering effect of tamoxifen may contribute to the cytostatic activity of the drug. The interrelationships between steroid hormone physiology and IGF-I physiology may have relevance to a variety of commonly used treatments for hormonally responsive cancers.

PMID: 1421427 [PubMed - indexed for MEDLINE]

[Dog-Slime]

What about raloxifene? It seems to block the estrogen receptors in breast tissue better than nolva, and has atleast as good of an effect on cholesterol levels... Does it also lower IGF?

[Merc..]

What about raloxifene? It seems to block the estrogen receptors in breast tissue better than nolva, and has atleast as good of an effect on cholesterol levels... Does it also lower IGF?

From the stuides I have seen it also lowers IGF.




Merc.

[anhukem]

If using tren I would consider using letro the entire cycle , from the start .... ( another benefit IMO is that letro has been shown to lower PgR )

Letro is strong and alot of people dont seem to like it ... Like I said I had to play with the dose ..


Merc.

what the dose of letro that you use?

[Merc..]

what the dose of letro that you use?

I used it @ .25 mg EOD ...



Merc.

[anhukem]

injectable? how do tou measure that? my source letro is 2.5mg/ml , what´s yours?

[Merc..]

injectable? how do tou measure that? my source letro is 2.5mg/ml , what´s yours?

Injectable ??? You mean liquid oral ?

I have a script from my doctor for letro .. It is pills dosed at 2.5 mg ..


Its a pain in the ass trying to cut the pill into .25 mg pieces.. I wish it was in liquid ( oral ) form as it would be much easier ..


Merc.

[anhukem]

i dont really know i never used it i will chek that with my source, that why im asking seemed strang to me to make .25mg of 2.5mg ...

[football2007]

yep, cutting that pill into 10 pieces has gotta be kinna hard.

Again, yes estrogen is beneficial, but I'd rather not grow boobs trying to get an extra pound or two of gains

[Dog-Slime]

Also, all this stuff about needing estrogen to build muscle either seems like it doesn't apply to me or some people (me) have much more aromatose going on inside them. On my first test only cycle (400mgs/week) I ran letro @ 1/4 ml (dosed at 2.5mgs/ml) which equals .625mgs ED and I still became bloated and started putting on fat pretty easily (I am naturally very skinny and can eat mcdonalds 3 times a day and still stay leaner than most). Also, my gyno (from puberty not steroids ) seemed to get a lil larger. I then bumped it up to 1/2 ml ED for a couple weeks, then bumped it up to a full ml ed for the duration of the cycle as it still seemed I was getting estrogenic sides. I know the letro was real (maybe underdosed?) but definately real as it did dry my joints out at higher doses. It was from the board sponsor. Luckily the combination of the high dose letro and then my nolva pct seemed to bring my gyno back down to where it was pre-cycle. I still gained over 25lbs on this cycle which only lasted 8 weeks (front-loaded). Much of this was fat tho which I contribute to estrogen as I said before I have never gained fat easily in my life and I was eating cleaner than I ever had before just higher cals. Anyways I think maybe bigger gains from not using an AI are from water weight and fat but even if that is not the case then guys who haven't cycled before should be really careful with not taking an AI. I knew I would be sensitive to it since I had gotten gyno from puberty but if someone was as sensitive as me and tried to run a cycle with no AI they would definately get gyno really quick.

[JasonR]

I've done 2 nearly identical cycles of test E 500mg, the second one had tbol in there but it has nothing to do with estro. anyway i got gyno only on my 2nd cycle.

Whyyy ? i waited 4 months between the cycles

[Merc..]

I've done 2 nearly identical cycles of test E 500mg, the second one had tbol in there but it has nothing to do with estro. anyway i got gyno only on my 2nd cycle.

Whyyy ? i waited 4 months between the cycles

Gyno needs estrogen to form as well as progesterone , GH and IGF .. Its not just estrogen... This is a good article on it...



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



INTRODUCTION
This chapter 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 (15).

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 (42).

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

ESTROGEN, GH AND IGF-1, PROGESTERONE, & PROLACTIN


Although estrogens and progestogens are vital to mammary growth, they are ineffective in the absence of anterior pituitary hormones (13). 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. (23, 40). 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 (49). 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.


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. (44, 25). 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 (17). Interestingly, treatment with an aromatase inhibitor leads to involution of the mammalian gland phenotype (27). 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" (42).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 (42).

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 (34). 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 (29).

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 (36). Thus, like the gynecomastia of obesity, the gynecomastia of aging may partly result from increased aromatase activity, causing increased circulating estrogen levels (7). 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 (30). 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 (38, 16).

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 (38).

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 (31).

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 (35).

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 (20, 50, 12). 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 (2). Furthermore, adrenal tumors can secrete excess dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione that can then be aromatized peripherally to estradiol.

Table 1.
Tumor type Hormone produced Aromatase overactivity
Leydig cell tumor testosterone
Sertoli cell tumor Estrogen + (in Peutz-Jegher Syndrome)
+ (in Carney complex)
Germ cell tumor b HCGestrogen
Granulosa cell tumor Estrogen
Adrenal tumors Dehydroepiandrosterone(DHEA), dehydroepiandrosterone-sulfate ( DHEA-S), andandrostenedione which are converted in the periphery to estrogens.

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 (5). 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. (43). 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 (42).

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. These drugs and their mechanisms will be addressed in a subsequent section.

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 (30). Lastly, enzyme deficiencies in the testosterone synthesis pathway from cholesterol also result in depressed 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 (7).

Secondary hypogonadism, if severe enough, results in low serum testosterone and unopposed estrogen effect from increased conversion of adrenal precursors to estrogens (30). 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 (42). 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 (18).

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 (13, 3, 37). 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 (18, 10).

Gynecomastia can also follow spinal cord disorders. Most patients with spinal cord disorders display depressed 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 (19).

Refeeding gynecomastia refers to breast development in men recovering from a malnourished state (15). 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 (30).

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. Examples of drugs that cause gynecomastia are listed in Tables 2 and 3. 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 (4, 14). Recreational use of marijuana, 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 (18, 39). 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 (9).

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 (8). 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 (45). In addition to decreasing testosterone levels and biologic effects, spironolactone also displaces estradiol from SHBG, increasing free estrogen levels. Ethanol 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 (30). Unfortunately, besides the drugs stated, a multitude of others cause gynecomastia by unknown mechanisms (Table 3).

Table 2. Drugs that induce gynecomastia by known mechanisms
Estrogen-
like, or binds to estrogen receptor Stimulate estrogen synthesis Supply aromatizable estrogen precursors Direct Testicular Damage Block testosterone synthesis Block androgen action Displace estrogen from SHBG
Estrogen vaginal cream Gonado-
tropins Exogenous androgen Busulfan Ketoconazole Flutamide Spironol-
actone
Estrogen-
containing embalming cream Growth Hormone Androgen precursors (ie androstene-
dione and DHEA) Nitrosurea Spironol-
actone Bicalut-
amide Ethanol
Delousing powder Vincristine Metronidazole Finasteride
Digitalis Ethanol Etomidate Cyproterone
Clomiphene Zanoterone
Marijuana Cimetidine
Ranitidine
Spironol-
actone



Table 3. 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 antidepressants
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 (21).

PATIENT EVALUATION

[Merc..]

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 (38, 16). 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.

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 (47). Dihydrotestosterone, a non-aromatizable androgen, has been used in patients with prolonged pubertal gynecomastia with good response rates (24). 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 (22). Unfortunately, undesirable side effects including edema, acne, and cramps have limited its use (30). Investigators have reported a 64 percent response rate with 100 mg/day of clomiphene citrate, a weak estrogen and moderate antiestrogen (26). 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 (1). 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 (46). 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 (30). An aromatase inhibitor, testolactone, has also been studied in an uncontrolled trial with promising effects (51). 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. (32)

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 deprivation 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 (11) (48).

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

[JasonR]

The article suggested that 1 option for treatment is taking tamoxifen twice a day at 10mg, I am currently taking it at 20mg ONCE day.
should i split the tabs.

THANKS FOR THE GREAT INFO.

[Merc..]

The article suggested that 1 option for treatment is taking tamoxifen twice a day at 10mg, I am currently taking it at 20mg ONCE day.
should i split the tabs.

THANKS FOR THE GREAT INFO.

Some doctors use nolva as an attempt to treat gyno.. The ones I have spoken to usually prescribe it 2 x per day.. I have never split the dose myself.. I take 20 mg per day in one dose ( when i use nolva )..



Merc.

[JasonR]

Can a single dose last for 24hrs in the body ? whats the half life for this drug

[Merc..]

Can a single dose last for 24hrs in the body ? whats the half life for this drug

The half life is 5-7 days I believe...



Merc.

[Merc..]

yep, cutting that pill into 10 pieces has gotta be kinna hard.

Again, yes estrogen is beneficial, but I'd rather not grow boobs trying to get an extra pound or two of gains

Merc.

[Marinos]

I understand everyone responds differently, but could you give a rough estimate as to how much more you could possibly gain without an AI?

If its only a couple of extra pounds, I'd personally want to play it safe.

[dece870717]

I've heard that Fareston (Toremifene Citrate) does not reduce IGF-1 levels, anyone know anything about that?

[Merc..]

I understand everyone responds differently, but could you give a rough estimate as to how much more you could possibly gain without an AI?

If its only a couple of extra pounds, I'd personally want to play it safe.

Yea thats kinda hard to answer as everyone is diffrent..



Merc.

[Merc..]

I've heard that Fareston (Toremifene Citrate) does not reduce IGF-1 levels, anyone know anything about that?

I have heard that also but I haven't researched it so I am not sure...


Merc.

[AnabolicBoy1981]

Also to note that estrogen causes more androgen sites in the muscle cells. It also increases GLUT-4 receptor activity which is responsible for glycogen storage and creatine uploading.
So to answer ones persons question about other anabolic mechanisms of estro, yeah, there are. So running GH and the like while on cycle with an AI will make up for some, but not all of the lowered estrogen effects.

Also to note about drugs that mess with estrogen...i believe certain antibiotics can. I was running only 200mg of test prop and needed to go on doxycycline for a possible tick bite, and my nipples became sensitive. I looked up doxycycline and it seems it inhibits estrogen from entering the intestine, which can cause the flora in the intestine to become unbalanced, which is why many similar antibiotics can cause GI tract disturbances for some. So my hypothesis was that since the estrogen uptake was not what it should be in my intestinal tissue, this left higher estrogen levels circulating in my body causing the gyno symtoms.

Trial and error is really the only way to figure this out unfortunetly, but when symptoms arise, just be sure to have stuff on hand to take care of it. thats all we can do. That and bloodwork. its tricky, but this is the game we play. oh well.

[Brent_G]

I can totally related to estrogen playing a key role in bodybuilding.

I had the same thing going on. I was using letro to combat estrogen related side effects.. basically just paranoid of gyno like most people.

My first cycle ever.. was just test. It was legit. Ran 500 mg a week. Wasnt getting much from it. Actually it really discourgaged my use of AAS. I was not very pleased with that cycle. Even bumped it up to 750mg a week towards the end.

Then i was reading about estrogen and role it plays in bodybuilding. And i did a cycle of 250mg a week of the same stuff i used before.

I gained SO MUCH more on the 250mg a week with no AI.

Letro is very strong and is what hindered my gains not to mention how bad my body ached all the time.

now i only use AI's at the beginning of a the cycle until the test kicks in and balances out. Only really get sides when the hormones are fluxuating so much. When they are stable there is no problems at all.

my 2 cents

[Merc..]

I can totally related to estrogen playing a key role in bodybuilding.

I had the same thing going on. I was using letro to combat estrogen related side effects.. basically just paranoid of gyno like most people.

My first cycle ever.. was just test. It was legit. Ran 500 mg a week. Wasnt getting much from it. Actually it really discourgaged my use of AAS. I was not very pleased with that cycle. Even bumped it up to 750mg a week towards the end.

Then i was reading about estrogen and role it plays in bodybuilding. And i did a cycle of 250mg a week of the same stuff i used before.

I gained SO MUCH more on the 250mg a week with no AI.

Letro is very strong and is what hindered my gains not to mention how bad my body ached all the time.

now i only use AI's at the beginning of a the cycle until the test kicks in and balances out. Only really get sides when the hormones are fluxuating so much. When they are stable there is no problems at all.

my 2 cents

What Ai do you like best ??




Merc.

[buffgator]

What doses of Adex do you use??



Merc.

I am using .25mg every day. I always ran it at .5mg every day, and that might have been overkill.

[Swifto]

....

[Merc..]

Yup.

Comparison of effects of the rise in serum testosterone by raloxifene and oral testosterone on serum insulin -like growth factor-1 and insulin-like growth factor binding protein-3.

Duschek EJ, Gooren LJ, Netelenbos C.

Department of Endocrinology, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected]

OBJECTIVE: In aging men serum levels of testosterone and insulin-like growth factor-1 (IGF-1) decline, potential factors in the reduced muscle strength, a**ominal obesity, sexual dysfunction and impaired general well being of aging. The partial oestrogen agonist and antagonist raloxifene increase serum testosterone levels in aging men, but the effect of raloxifene on serum IGF-1 levels in men is unknown. In this study the effects of raloxifene on IGF-1 levels and the associated increase in serum testosterone were compared to the effects of oral testosterone supplementation. DESIGN AND PATIENTS: Thirty healthy elderly men between 60 and 70 years received raloxifene 120 mg/day or placebo in a randomised double blind fashion for 3 months. Secondly, seven female to male (F to M) transsexuals undergoing hormonal sex reassignment received testosterone undecanoate 160 mg/day. Measurement: At baseline and after three months serum levels of testosterone, IGF-1 and its most important binding protein, IFGBP-3 was measured. In the group transsexuals also serum gonadotrophins and 17beta-oestradiol was measured. RESULTS: Compared to placebo raloxifene increased serum testosterone by 20% but it decreased serum IGF-1 levels by 24.5% (95% confidence interval (CI): -13.0 to -36.1%). No significant change in serum IGFBP-3 levels was found. The effect of raloxifene on serum IGF-1 has been observed with other oral oestrogens, and, therefore, is likely to be ascribed to the partial oestrogen agonist activity of raloxifene. In the F to M transsexuals, serum testosterone levels increased from median <1.0 nmol/l to 6.2 nmol/l, without significant changes in serum gonadotrophins and 17beta-oestradiol levels. Serum IGF-1 levels increased by 12.1% (95% CI: 1.9-22.3%) versus baseline. No effect was observed on serum IGFBP-3 levels. CONCLUSION: Both raloxifene and oral testosterone increased serum testosterone, but raloxifene significantly decreased serum IGF-1 levels without affecting IGFBP-3. By contrast, oral testosterone supplementation in F to M transsexuals increased IGF-1 levels. In both treatment groups no significant change in serum IGFBP-3 was found.


Nice post Merc.

While this thread is pro-estorgen I'd like to say there is a flip side and thats PCT. Estorgen is very suppressive and may effect the leydig cells directly, as Vitor pointed out.

If you dont want to use an AI during your cycle, use it for the last 4-5 weeks IMHO, to get estorgen down before your PCT commences. This, in theory should help with your recovery.

I use an AI when "on" aromotasables. But at a low dose. Perhaps, 0.5mg/EOD or E2D of Arimidex . Get it in normal ranges, but dont completely kill it off.

Another thing to note is AI's and SERM's arnt very friendly drugs to the body. If you can avoid using them, avoid using them. Simple.

Thanks for posting that study Swifto..


Merc.

[NOZ]

Good post Merc

[Swifto]

....

[Merc..]

No problem.

While the subject was just raised here, about SERM's and increasing the PgR.

What do you make of this Merc?


Sanchez-Criado JE, de Las Mulas JM, Bellido C, Aguilar R, Garrido-Gracia JC.

Department of Cellular Biology, University of Cordoba, Cordoba, Spain. [email protected]

The selective oestrogen receptor modulator (SERM) tamoxifenWhile RX had no effect on these parameters


Perhaps Rolax doesnt increase the PgR?

Interesting .. Do you have any other studies on this ?? Animal studies are indeed relevant but there is probably some human studies done on this as well..


Merc.

[Swifto]

Interesting .. Do you have any other studies on this ?? Animal studies are indeed relevant but there is probably some human studies done on this as well..


Merc.

Not at present. I know Kratos knows about this subject too.

I'll have to search around on pubmed tomorrow.

[JasonR]

Alot of people report lumps and swollen puffy nipples while ON Nolva and other ANTI E's (which were gone after pct). this leads me to believe that a true balance and a sides free body can only be achieved when all hormonal supplementation is seized and the endocrine is fully recovered. that is why 13 year old children's gyno will most of the time sort itself out after few years.
For the steroid user though, its a matter of weeks and months.

[Merc..]

Not at present. I know Kratos knows about this subject too.

I'll have to search around on pubmed tomorrow.