Short ester test .vs. Long Ester for cutting

[Giantz11]

J Clin Endocrinol Metab. 2005 Jun;90(6):3592-9.

Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise.

Hamadeh MJ, Devries MC, Tarnopolsky MA.

Department of Pediatrics and Medicine, McMaster University Medical Center, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.

Healthy active men exhibit higher rates of carbohydrate (CHO) and leucine oxidation and lower rates of lipid oxidation compared with their female counterparts both at rest and during moderate intensity endurance exercise. We postulated that this reduced dependence on amino acids as a fuel source in women was due to the female sex hormone estrogen. In a randomized, double-blind, placebo-controlled, cross-over design, we investigated the effect of supplementing 12 recreationally active men with estrogen on whole body substrate oxidation and leucine kinetics at rest and during moderate intensity endurance exercise. Subjects cycled for 90 min at an intensity of 65% maximum O(2) consumption after 8 d of either estrogen supplementation (2 mg 17beta-estradiol/d) or placebo (polycose). After a 2-wk washout period, they repeated the test after 8 d of the alternate treatment. On the test day, after a primed continuous infusion of l-[(13)C]leucine, O(2) consumption, CO(2) production, steady-state breath (13)CO(2), and plasma alpha-[(13)C]ketoisocaproate enrichments were measured at rest and at 60, 75, and 90 min during exercise in the postabsorptive state. Exercise increased energy expenditure more than 5-fold, CHO oxidation more than 6-fold, lipid oxidation more than 4-fold, and leucine oxidation 2.2-fold (all P < 0.0001), whereas it decreased the ratio of lipid to CHO oxidation by 50-70% (P = 0.003) compared with values at rest. Estrogen supplementation decreased respiratory exchange ratio during exercise (P = 0.03). Estrogen supplementation significantly decreased CHO oxidation by 5-16% (P = 0.04) and leucine oxidation by 16% (P = 0.01), whereas it significantly increased lipid oxidation by 22-44% (P = 0.024) at rest and during exercise. We conclude that estrogen influences fuel source selection at rest and during endurance exercise in recreationally active men, characterized by a reduced dependence on amino acids and CHO and an increased reliance on lipids

[Giantz11]

Int J Obes Relat Metab Disord 2002 Aug;26(8):1103-9

Estrogen receptor beta is involved in the anorectic action of estrogen.

OBJECTIVE: Estrogen has been implicated in feeding behavior and adiposity. This study was undertaken to elucidate the mechanism underlying the anti-obesity and anorectic action of estrogen and the role of estrogen receptor (ER) in the central nervous system. METHODS AND RESULTS: Ovariectomy in 8-week-old female Wistar rats induced hyperphagia along with an increase in body weight and abdominal fat accumulation compared to control sham-operated rats. These changes were fully reversed by subcutaneous replacement of estradiol and were abrogated by pair-feeding. Then, the effects of intracerebroventricular infusion of estradiol, alone or in combination with antisense oligodeoxynucleotides (ODN), for ER in ovariectomized rats were examined. The estradiol group showed 10-20% lower daily food intake, and after the 2-week infusion period a 14% reduction in body weight with a similar reduction in abdominal fat compared to the vehicle group. The inhibitory effect of estradiol on food intake and body weight was blocked by co-administration of ER-beta antisense ODN, whereas ER-alpha antisense ODN did not show any influence. CONCLUSION: These results indicate that ER-beta in the central nervous system is involved in the anorectic action of estrogen.

[Giantz11]

Int J Obes Relat Metab Disord 1996 Apr;20(4):291-302 Related Articles, Links


The regulation of adipose tissue distribution in humans.

Bjorntorp P.

Department of Heart and Lung Disease, Sahlgren's Hospital, University of Goteborg, Sweden.

The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. With visceral fat accumulation multiple endocrine perturbations are found, including elevated cortisol and androgens in women, as well as low growth hormone (GH) and, in men, testosterone (T) secretion. These abnormalities probably derive from a hypersensitive hypothalamo-pituitary-adrenal axis, with hyperinsulinemia related to a marked insulin resistance as a consequence. These hormonal changes exert profound effects on adipose tissue metabolism and distribution. At the adipocyte level cortisol and insulin promote lipid accumulation by expressing lipoprotein lipase activity, while T, GH and probably estrogens exert opposite effects. The consequences will most likely be more expressed in visceral than subcutaneous adipose tissues because of a higher cellularity, innervation and blood flow.
...the functional effects of estrogens in women are similar to those of T in men. The mechanisms are, however, probably indirect because of the apparent absence of specific estrogen and progesterone receptors in human adipose tissue. This interpretation from the studies referred to above fits well with physiological, and clinical conditions with increased visceral fat mass, where the balance between the lipid accumulating hormone couple (cortisol and insulin) and the hormones which prevent lipid accumulation and instead activate lipid mobilization pathways (sex steroid hormones and GH) is shifted to the advantage of the former...

[Giantz11]

A Few Common Bodybuilding Myths
by Nandi


Based on my experience of having been either a moderator or administrator on three Anabolic Fitness boards, I’ve put together a collection of what I feel are, for lack of a better term, a few of the most prevalent “bodybuilding myths.” These are topics that are discussed often and at great length, usually accompanied by much misinformation. In some cases “myth” might be an inappropriate term. A better term might be “bodybuilding dogma based on little or no evidence.” Some might even argue that is unfair in some cases, and that these are simply “controversial topics.” These are not myths held by the general public about bodybuilders and drugs, such as “anabolic steroids invariably cause ‘roid rage ,’ or anabolic steroids lead to permanent impotence. They are rather what I believe are widespread misconceptions within the bodybuilding community itself about problems encountered and practices employed by the participants themselves.



ESTROGENIC FAT


Estrogen makes a person fat, doesn’t it? Well, women do have a higher body fat content in general than do men, especially in the gluteofemoral (hips and buttocks) region. Is estrogen really the cause of this gender dimorphism in adiposity? Probably not. In fact, there are a wealth of data that implicate estrogen as both an anorectic and antiadipogenic hormone. It is much more likely that progesterone is the culprit in supporting higher levels of gluteofemoral fat in women (1). The model described in (1) has progesterone as the lipogenic hormone. Before menopause, both estrodiol and progesterone are secreted by the ovaries. After menopause, estrone becomes the primary circulating estrogen produced from aromatization of adrenal androgens (primarily the aromatization of androstenedione to estrone by adipose tissue), while progesterone levels drop dramatically since adrenal production of progesterone is minimal.

In premenopausal women, progesterone increases lipoprotein lipase activity, which is greater in the gluteofemoral region, while estrogen suppresses it. Lipoprotein lipase is the body’s primary fat storage enzyme; it is responsible for allowing fats to leave the circulation and enter adipocytes. The progesterone wins out however and before menopause, women tend to have more gluteofemoral fat and less abdominal fat.

Why do women have more gluteofemoral fat while men have more central (abdominal) fat? One popular theory is that women hold fat in the gluteofemoral region where it is far removed from the liver and has fewer fat mobilizing enzymes/more fat retaining enzymes than in men. Men hold fat in the visceral and abdominal subcutaneous region where it is closer to the liver and richer in fat mobilizing enzymes. Proximity to the liver is a factor because the portal circulation connects abdominal fat deposits directly to the liver. Free fatty acids released from abdominal deposits can act directly on the liver to promote gluconeogenesis, providing the body with a ready supply of glucose for “fight or flight” situations.

From an adaptational viewpoint, women's fat is designed to be stored until needed for lactation and child rearing. Men's fat on the other hand is designed to be readily mobilized for fight or flight situations during defense and hunting. This theory may be a bit simplistic as well as sexist; but it does make sense to some degree.

Most likely the notion of estrogenic fat originated from the belief that estrogen upregulates alpha 2 receptors in fat cells, retarding lipolysis. This may be just one facet of estrogen’s actions. If one looks at the net result of estrogen’s effects, to quote a leading expert in the field


“Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Oestrogens seem to exert net effects similar to those of testosterone.” (2)

For example, animal studies have shown that testosterone promotes alpha 2 adrenoreceptor mediated antilipolytic activity, just as it promotes beta adrenoreceptor mediated lipolysis.

Interestingly, recent research has even attributed at least part of testosterone's fat burning properties to its local aromatization to estradiol (3). For instance when testosterone is administered along with an aromatase inhibitor, LPL activity increases, showing that the testosterone itself is devoid of any ability to lower LPL. (4)

There are a number of animal studies where estradiol administration led to significant weight and fat loss. Citing just one, for example:


"The administration of 17 beta-estradiol (500 micrograms/kg, 2 or 4 weeks) to male rats significantly reduced the body weight...Basal lipolysis and adren****e-induced lipolysis [due to increase in HSL action] were also significantly enhanced in the epididymal adipose tissue from the male rat treated either with 7 mg/kg estradiol 12 h ahead or with 500 micrograms/kg estradiol for 2 weeks. These results indicate that estradiol exerts strong effects on metabolism of the adipose and these effects seems to be mediated through cyclic-AMP." (5)

This research indicates that in addition to the abovementioned inhibition of LPL, estrogen also stimulates the lipolytic enzyme hormone sensitive lipase.

Some of the most compelling evidence for the antiadipogenic effect of estrogen in both males and females comes from studies of estrogen receptor knockout mice and humans with aromatase deficiency. Both the afflicted humans and the knockout mice exhibit obesity. A detailed look at this topic can be found here:




I also mentioned that estrogen is a potent hunger-suppressing hormone. Research is a bit sketchier here, but the effect is thought to be due to an estrogen-induced inhibition in melanin-concentrating hormone (MCH) sign****g (6). MCH is a neuropeptide found in the hypothalamus that is also thought to be involved in leptin’s regulation of appetite. Leptin, an anorectic hormone secreted from the adipose tissue, acts on the specific receptor present on its target neurons in the brain, and suppresses the expression of both MCH and its receptor. So we see that the actions of both estrogen and leptin are at least partly mediated through interactions with MCH.

[magic32]

I for one want to keep water down for the entire cutting cycle as I want to be able to wash my Osh Kosh Jammies on my abs. That and be able to $hit on everyone in a 1 mile radius when at the beach.

Best Serm or AI for Jay's goal above if the cycle is TEST E? Letro? If so at what dosage?
M.

[Pinnacle]

Best Serm or AI for Jay's goal above if the cycle is TEST E? Letro? If so at what dosage?
M.

Aromasin ,hands down


~Pinnacle~

[Magnum II]

I've had my best cutting successes running Test Cyp with T3 for 12 weeks.
If Var is available to me, I'll throw that in during the last 8 weeks. T3 seems to be extra catabolic for me. In the past when I've run Test Prop with it, I came away not just with lower body fat but clearly with a loss of muscle tissue. Not entirely sure what the bio processes are that make this true for me, just saying from experience...give me the long-acting ester anyday when I'm running T3.

[IBdmfkr]

Aromasin ,hands down


~Pinnacle~

Why do you say this Pinn, I have yet to find any solid info on this compound, yet at the same time I'm taking it and Love it, Vascular as hell and on 100mg of Drol/day. Me likey.

[Pinnacle]

Why do you say this Pinn, I have yet to find any solid info on this compound, yet at the same time I'm taking it and Love it, Vascular as hell and on 100mg of Drol/day. Me likey.

Some ppl read and do thier homework,while others prefer to piggy back

[IBdmfkr]

lol, I have found some good articles from various sites but they all say the same thing, I'm talking more personal experiences with the drug, not many people have much to say in that case, sorry if my post was misinterpretted.

[magic32]

Aromasin ,hands down


~Pinnacle~

Thanks Pinn.

M.

[GoldieTheMack]

Aromasin ,hands down


~Pinnacle~

Bump.

But at what dosage would you run it?
Gold

[Pinnacle]

Bump.

But at what dosage would you run it?
Gold

20 mg ED.......

[GoldieTheMack]

Thank you.
Gold

[magic32]

lol, I have found some good articles from various sites but they all say the same thing, I'm talking more personal experiences with the drug, not many people have much to say in that case, sorry if my post was misinterpretted.

Not hard to find, take a gander...

Aromasin / British Dragon

Generic name: Exemestane

Aromasin is the trade name for Exemestane. In some cases, health care professionals may use the trade name Aromasin when referring to the generic drug name Exemestane.

Drug type: Aromasin is a hormone therapy. Aromasin is classified as an "aromatase inhibitor." (For more detail see "How this drug works" below).

What this drug is used for:

Exemestane is used to treat advanced breast cancer in post-menopausal women whose disease has progressed following tamoxifen therapy.
Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How this drug is given:

This drug is taken by mouth, in tablet form, once a day
This medication should be taken after a meal
Side effects:
Important things to remember about the side effects of exemestane:

Most people do not experience all of the side effects listed.
Side effects are often predictable in terms of their onset and duration.
Side effects are almost always reversible and will go away after treatment is complete.
There are many options to help minimize or prevent side effects.
There is no relationship between the presence or severity of side effects and the effectiveness of the medication.
The following side effects are common (occurring in greater than 30%) for patients taking exemestane:

Note: There are no common side effects of exemestane.

These side effects are less common side effects (occurring in about 10-29%) of patients receiving Exemestane:

Fatigue
Nausea (mild).
Hot flashes (see sexuality)
Depression
Bone pain
Insomnia (see sleeping problems)
Anxiety
Shortness of breath (see lung problems)
Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

Shortness of breath or difficulty breathing
Having thoughts or feeling like you may want to harm yourself or others
The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

Nausea (interferes with ability to eat and unrelieved with prescribed medication)
Extreme fatigue (unable to carry on self-care activities)
Depressed (interfering with your ability to carry on your regular activities)
Always inform your health care provider if you experience any unusual symptoms.

Precautions:
For both men and women: Do not conceive a child (get pregnant) while taking exemestane. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
Do not breast feed while taking this medication.
Self-care tips:

Take this medication after a meal; at about the same time every day.
This medication causes little nausea. But if you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals. Sucking on lozenges and chewing gum may also help.
In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
If you are experiencing hot flashes, wearing light clothing, staying in a cool environment, and putting cool cloths on your head may reduce symptoms. Consult you health care provider if these worsen, or become intolerable.
Acetaminophen or ibuprophen may help relieve discomfort from fever, headache and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.
Get plenty of rest.
Maintain good nutrition.
If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.
Monitoring and testing:

You will be monitored regularly by your doctor while you are taking anastrozole, but no special tests are required.

How this drug works:

Hormones are chemical substances that are produced by glands in the body, which enter the bloodstream and cause effects in other tissues. For example, the hormone testosterone made in the testicles and is responsible for male characteristics such as deepening voice and increased body hair. The use of hormone therapy to treat cancer is based on the observation that receptors for specific hormones that are needed for cell growth are on the surface of some tumor cells. Hormone therapies work by stopping the production of a certain hormone, blocking hormone receptors, or substituting chemically similar agents for the active hormone, which cannot be used by the tumor cell. The different types of hormone therapies are categorized by their function and/or the type of hormone that is affected.

Exemestane is an aromatase inhibitor. This means it blocks the enzyme aromatase (found in the body's muscle, skin, breast and fat), which is used to convert androgens (hormones produced by the adrenal glands) into estrogen. In the absence of estrogen, tumors dependent on this hormone for growth will shrink.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.


AROMASIN®(exemestane) Tablets

DESCRIPTION:
AROMASIN® Tablets for oral administration contain 25 mg of exemestane, an irreversible, steroidal aromatase inactivator. Exemestane is chemically described as 6-methylenandrosta-1,4-diene-3,17 -dione. Its molecular formula is C20H2402and its structural formula is as follows:

the active ingredient is a white to slightly yellow crystalline powder with a molecular weight of 296.41. Exemestane is freely soluble in N, N-dimethylformamide, soluble in methanol, and practically insoluble in water.

Each AROMASIN Tablet contains the following inactive ingredients: mannitol, crospovidone, polysorbate 80, hydroxypropyl methylcellulose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.

CLINICAL PHARMACOLOGY

Mechanism of Action
Breast cancer cell growth may be estrogen-dependent. Aromatase(exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer.

Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as “suicide inhibition.” Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.

Pharmacokinetics
Following oral administration to healthy postmenopausal women, exemestane is rapidly absorbed. After maximum plasma concentration is reached, levels decline polyexponentially with a mean terminal half-life of about 24 hours. Exemestane is extensively distributed and is cleared from the systemic circulation primarily by metabolism. the pharmacokinetics of exemestane are dose proportional after single (10 to 200 mg) or repeated oral doses (0.5 to 50 mg). Following repeated daily doses of exemestane 25 mg, plasma concentrations of unchanged drug are similar to levels measured after a single dose.

Pharmacokinetic parameters in postmenopausal women with advanced breast cancer following single or repeated doses have been compared with those in healthy, postmenopausal women. Exemestane appeared to be more rapidly absorbed in the women with breast cancer than in the healthy women, with a mean tmaxof 1.2 hours in the women with breast cancer and 2.9 hours in the healthy women. After repeated dosing, the average oral clearance in women with advanced breast cancer was 45% lower than the oral clearance in healthy postmenopausal women, with corresponding higher systemic exposure. Mean AUC values following repeated doses in women with breast cancer (75.4 ng®h/mL) were about twice those in healthy women

(41.4 ng®h/mL).

Absorption: Following oral administration of radiolabeled exemestane, at least 42% of radioactivity was absorbed from the gastrointestinal tract. Exemestane plasma levels increased by approximately 40% after a high-fat breakfast. Distribution:Exemestane is distributed extensively into tissues. Exemestane is 90% bound to plasma proteins and the fraction bound is independent of the total concentration. Albumin and a1-acid glycoprotein both contribute to the binding. the distribution of exemestane and its metabolites into blood cells is negligible.

Metabolism and Excretion:Following administration of radiolabeled exemestane to healthy postmenopausal women, the cumulative amounts of radioactivity excreted in urine and feces were similar (42 – 3% in urine and 42 – 6% in feces over a 1-week collection period). the amount of drug excreted unchanged in urine was less than 1% of the dose.

Exemestane is extensively metabolized, with levels of the unchanged drug in plasma accounting for less than 10% of the total radioactivity. the initial steps in the metabolism of exemestane are oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. Each metabolite accounts only for a limited amount of drug-related material. the metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug. One metabolite may have androgenic activity (see Pharmacodynamics, Other Endocrine Effects). Studies using human liver preparations indicate that cytochrome P-450 3A4 (CYP 3A4) is the principal isoenzyme involved in the oxidation of exemestane.

Special Populations
Geriatric: Healthy postmenopausal women aged 43 to 68 years were studied in the pharmacokinetic trials. Age-related alterations in exemestane pharmacokinetics were not seen over this age range. Gender:the pharmacokinetics of exemestane following administration of a single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean age 55 years). Race:the influence of race on exemestane pharmacokinetics has not been evaluated. Hepatic Insufficiency: the pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers. (See Precautions) Renal Insufficiency:the AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers (see Precautions). Pediatric:the pharmacokinetics of exemestane have not been studied in pediatric patients.

Drug-Drug Interactions
Exemestane is metabolized by cytochrome P-450 3A4 (CYP 3A4) and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4. In a clinical pharmacokinetic study, ketoconazole showed no significant influence on the pharmacokinetics of exemestane. Although no other formal drug-drug interaction studies have been conducted, significant effects on exemestane clearance by CYP isoenzymes inhibitors appear unlikely. However, a possible decrease of exemestane plasma levels by known inducers of CYP 3A4 cannot be excluded.

Pharmacodynamics
Effect on Estrogens:Multiple doses of exemestane ranging from 0.5 to 600 mg/day were administered to postmenopausal women with advanced breast cancer. Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85% to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body aromatization (as measured by injecting radiolabeled androstenedione) by 98% in postmenopausal women with breast cancer. After a single dose of exemestane 25 mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after dosing and persisted for 4 to 5 days. Effect on Corticosteroids:In multiple-dose trials of doses up to 200 mg daily, exemestane selectivity was assessed by examining its effect on adrenal steroids . Exemestane did not affect cortisol or aldosterone secretion at baseline or in response to ACth at any dose. thus, no glucocorticoid or mineralocorticoid replacement therapy is necessary with exemestane treatment. Other Endocrine Effects:Exemestane does not bind significantly to steroidal receptors, except for a slight affinity for the androgen receptor (0.28% relative to dihydrotestosterone). the binding affinity of its 17-dihydrometabolite for the androgen receptor, however, is 100-times that of the parent compound. Daily doses of exemestane up to 25 mg had no significant effect on circulating levels of testosterone , androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxy-progesterone. Increases in testosterone and androstenedione levels have been observed at daily doses of 200 mg or more. A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with daily exemestane doses of 2.5 mg or higher. Slight, nondose-dependent increases in serum lutenizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed even at low doses as a consequence of feedback at the pituitary level.

CLINICAL STUDIES
Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.


Table 1. Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen therapy

Parameter AROMASIN Megestrol Acetate
(N = 366) (N = 403)
Median Age (range) 65 (35-89) 65 (30-91)
ECOG Performance Status
0 167 (46%) 187 (46%)
1 162 (44%) 172 (43%)
2 34 (9%) 42 (10%)
Receptor Status
ER and/or PgR + 246 (67%) 274 (68%)
ER and PgR unknown 116 (32%) 128 (32%)
Responders to prior tamoxifen 68 (19%) 85 (21%)
NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis
Visceral – other sites 207 (57%) 239 (59%)
Bone only 61 (17%) 73 (18%)
Soft tissue only 54 (15%) 51 (13%)
Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen therapy
Adjuvant or Neoadjuvant 145 (40%) 152 (38%)
Advanced Disease, Outcome
Prior Chemotherapy
For advanced disease – adjuvant 58 (16%) 67 (17%)
Adjuvant only 104 (28%) 108 (27%)
No chemotherapy 203 (56%) 226 (56%)

the efficacy results from the comparative study are shown in Table 2. the objective response rates observed in the two treatment arms showed that AROMASIN(exemestane) was not different from megestrol acetate. Response rates for exemestane from the two single-arm trials were 23.4% and 28.1%.

Table 2. Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifentherapy

AROMASIN Megestrol
Response Characteristics (N=366) acetate (N=403)
Difference in Response Rate (AR-MA) 2.6
95% C. I. 7.5, -2.3
CR (%) 2.2 1.2
SD ‡ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
Hazard Ratio (AR-MA) 0.84


there were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. the Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 1.

CONTRAINDICATIONS
AROMASIN(exemestane) Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.

PRECAUTIONS
General.AROMASIN(exemestane) Tablets should not be administered to premenopausal women. AROMASIN should not be coadministered with estrogen-containing agents as these could interfere with its pharmacologic action.

Hepatic Insufficiency. the pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers. the safety of chronic dosing in patients with moderate or severe hepatic impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.

Renal Insufficiency.the AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers. the safety of chronic dosing in patients with moderate or severe renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.

Laboratory Tests.Approximately 20% of patients receiving exemestane in clinical studies,experienced Common Toxicity Criteria (CTC) grade 3 or 4 lymphocytopenia. Of these patients, 89% had a pre-exisiting lower grade lymphopenia. Forty percent of patients either recovered or improved to a lesser severity while on treatment. Patients did not have a significant increase in viral infections, and no opportunistic infections were observed. Elevations of serum levels of AST, ALT, alk****e phosphatase and gamma glutamyl transferase> 5 times the upper value of the normal range (i.e., ‡ CTC grade 3) have been rarely reported but appear mostly attributable to the underlying presence of liver and/or bone metastases. In the comparative study, CTC grade 3 or 4 elevation of gamma glutamyl transferase without documented evidence of liver metastasis was reported in 2.7% of patients treated with AROMASIN(exemestane) and in 1.8% of patients treated with megestrol acetate.

Drug Interactions.Exemestane is extensively metabolized by CYP3A4, but coadministration of ketoconazole, a potent inhibitor of CYP 3A4, has no significant effect on exemestane pharmacokinetics. Significant pharmacokinetic interactions mediated by inhibition of CYP isoenzymes therefore appear unlikely; however, a possible decrease of exemestane plasma levels by known inducers of CYP 3A4 cannot be excluded (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Drug/ Laboratory Tests Interactions.No clinically relevant changes in the results of clinical laboratory tests have been observed.

Carcinogenesis, Mutagenesis, Impairment of Fertility.Carcinogenicity studies have not been conducted with exemestane. Exemestane was not mutagenic in bacteria (Ames test) or mammalian cells (V79 Chinese hamster lung cells). Exemestane was clastogenic in human lymphocytes in vitro without metabolic activation but was not clastogenic in vivo (micronucleus assay in mouse bone marrow). Exemestane did not increase unscheduled DNA synthesis in rat hepatocytes.

Untreated female rats showed reduced fertility when mated to males treated with 500 mg/kg/day exemestane (approximately 200 times the recommended human dose on a mg/m2basis) for 63 days prior to and during cohabitation. Exemestane given to female rats 14 days prior to mating and through day 15 or 20 of gestation increased the placental weights at 4 mg/kg/day (approximately 1.5 times the human dose on a mg/m2basis). Exemestane showed no effects on female fertility parameters (e.g., ovarian function, mating behavior, conception rate) in rats given doses up to 20 mg/kg/day (approximately 8 times the human dose on a mg/m2basis), but mean litter size was decreased at this dose. In general toxicology studies, changes in the ovary, including hyperplasia, an increase in ovarian cysts and a decrease in corpora lutea were observed with variable frequency in mice, rats and dogs at doses that ranged from 3-20 times the human dose on a mg/m2basis.

Pregnancy.Pregnancy Category D. See WARNINGS.

Nursing Mothers.AROMASIN(exemestane) is only indicated in postmenopausal women. However, radioactivity related to exemestane appeared in rat milk within 15 minutes of oral administration of radiolabeled exemestane. Concentrations of exemestane and its metabolites were approximately equivalent in the milk and plasma of rats for 24 hours after a single oral dose of 1 mg/kg 14C-exemestane. It is not known whether exemestane is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if a nursing woman is inadvertently exposed to AROMASIN (see WARNINGS).

Pediatric Use. the safety and effectiveness of AROMASIN(exemestane) in pediatric patients have not been established.

Geriatric Use.the use of AROMASIN(exemestane) in geriatric patients does not require special precautions.

ADVERSE REACTIONS
A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Exemestane was generally well tolerated, and adverse events were usually mild to moderate. Only one death was considered possibly related to treatment with exemestane; an 80-year-old women with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse events, mainly within the first 10 weeks of treatment; late discontinuations because of adverse events were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN(exemestane) and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN discontinued treatment because of adverse events than those treated with megestrol acetate (2% versus 5%). Adverse events that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%). the proportion of patients experiencing an excessive weight gain (>10% of their baseline weight) was significantly higher with megestrol acetate than with AROMASIN (17% versus 8%). Table 3 shows the adverse events of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN or megestrol acetate.

Table 3. Incidence (%) of Adverse Events of all Grades* and Causes Occurring in 5% of Patients In Each Treatment Arm in the Comparative Study

AROMASIN Megestrol 25 mg Acetate Event once daily 40 mg QID (N=358) (N=400)

Autonomic Nervous
Increased sweating 6 9

Body as a Whole

Fatigue 22 29 Hot flashes 13 6 Pain 13 13 Influenza-like symptoms 6 5 Edema (includes edema, peripheral edema, leg edema) 7 6

Cardiovascular
Hypertension 5 6

Nervous
Depression 13 9 Insomnia 11 9 Anxiety 10 11 Dizziness 8 6 Headache 8 7

Gastrointestinal

Nausea, Vomiting, Abdominal pain, Anorexia, Constipation, Diarrhea, Increased appetite,Respiratory Dyspnea, Coughing.

* Graded according to Common Toxicity Criteria

Less frequent adverse events of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN(exemestane) 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture; bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse events of any cause observed in the overall clinical trials program (N = 1058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%) and fever (5%). Adverse events of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.

OVERDOSAGE
Clinical trials have been conducted with exemestane given as a single dose to healthy female volunteers at doses as high as 800 mg and daily for 12 weeks to postmenopausal women with advanced breast cancer at doses as high as 600 mg. these dosages were well tolerated. there is no specific antidote to overdosage and treatment must be symptomatic. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

A male child (age unknown) accidentally ingested a 25-mg tablet of exemestane. the initial physical examination was normal, but blood tests performed 1 hour after ingestion indicated leucocytosis (WBC 25000/mm3with 90% neutrophils). Blood tests were repeated 4 days after the incident and were normal. No treatment was given.

In mice, mortality was observed after a single oral dose of exemestane of 3200 mg/kg, the lowest dose tested (about 640 times the recommended human dose on a mg/m2basis). In rats and dogs, mortality was observed after single oral doses of exemestane of 5000 mg/kg (about 2000 times the recommended human dose on a mg/m2basis) and of 3000 mg/kg (about 4000 times the recomme nded human dose on a mg/m2basis), respectively.

Convulsions were observed after single doses of exemestane of 400 mg/kg and 3000 mg/kg in mice and dogs (approximately 80 and 4000 times the recommended human dose on a mg/m2basis), respectively.

DOSAGE AND ADMINISTRATION
the recommended dose of AROMASIN(exemestane) Tablets is 25 mg once daily after a meal. Treatment with AROMASIN should continue until tumor progression is evident.

the safety of chronic dosing in patients with moderate or severe hepatic or renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary (see CLINICAL PHARMACOLOGY, Special Populations and PRECAUTIONS).

HOW SUPPLIED
AROMASIN(exemestane) Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. the tablets are printed on one side with the number “7663” in black. AROMASIN is packaged in either HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets, or in Aluminium-PVDC/PVC-PVDC opaque white blisters, supplied in packs of 30 tablets.

M.

[magic32]

PINNACLE,

Did you notice any sides from Aro?

M.

[IBdmfkr]

Not hard to find, take a gander...

That's nice, I have read all the studies and profiles on this compound, I am speaking of personal experiences from users/members and their results. Thanks for the post though but I have 10pages of it on my harddrive from different sources.

lol, I have found some good articles from various sites but they all say the same thing, I'm talking more personal experiences with the drug, not many people have much to say in that case, sorry if my post was misinterpretted.

Btw all these studies you posted and that I have found are either on (rats, postmenopausal women, breast cancer patients, basically no one in the bodybuilding field or atheletes).

[Pinnacle]

Btw all these studies you posted and that I have found are either on (rats, postmenopausal women, breast cancer patients, basically no one in the bodybuilding field or atheletes).

And why would science do studies on athletes using aromasin ?What financial gains could they get from doing so?Because it hasn't been/nor probably won't be studied with athletes,does that make the drug less credible than letro or liquidex,or Nolvadex (which I've yet to see studies done with athletes)?

What's your point then?

~Pinnacle~

[rodge]

i did a contest cutter on long acting esters. remind you that it was done before i found out this great educational place

it was an 14 weeker containing:

500mg sustanon ew
500mg test-e ew
400mg deca ew
50mg winny eod
10mg nolva ed

last week for the show i dropped the sust/test-e/deca and toke 250mg test prop and 50mg drol untill the day before the show.

result...

[Pinnacle]

PINNACLE,

Did you notice any sides from Aro?

M.

I've only used it once for a short period of time(20 mgs)...answer is NO adverse sides at all.

~Pinnacle~

[IBdmfkr]

I was simply asking for user experiences, get your panties out of a bunch. Actually forget I asked, I'll see for myself.

[magic32]

I was simply asking for user experiences, get your panties out of a bunch. Actually forget I asked, I'll see for myself.

No offense man, we all love you here! I've learned more than a thing or two from your threads/posts!


M.

[IBdmfkr]

No prob, it just seems not many members have experience with this particular compound, User experience means much more to me then pubmed articles and other medical journals. That's why we are here to discuss it, otherwise we could just sit and read all day about rats taking steroids . lol

[Giantz11]

i did a contest cutter on long acting esters. remind you that it was done before i found out this great educational place

it was an 14 weeker containing:

500mg sustanon ew
500mg test-e ew
400mg deca ew
50mg winny eod
10mg nolva ed

last week for the show i dropped the sust/test-e/deca and toke 250mg test prop and 50mg drol untill the day before the show.

result...

I don't know if its just me but I'd say you got pretty damn ripped Rodge!

But damn that Winny was tough on the hair line

[rodge]

I don't know if its just me but I'd say you got pretty damn ripped Rodge!

But damn that Winny was tough on the hair line

i def did get me ripped but at this moment i'm also in contest prep and this time i'm gonna try the more common aas used for it like var/mast/prop/winny. can't wait to see how that goes.

whats wrong with my hairline

-rodge

[novicenovicen]

what a great thread. Bump for all to read. should be stickied.

[Warrior]

Here is a good read from Bill Roberts regarding steroids ' esters...

How do esters change the physical properties of steroids?

Testosterone , nandrolone , and other anabolic steroids have poor solubility in either water or oil. Esterifying them improves oil solubility. This enables useful dosages of perhaps 100 mg or more per cc. But the more carbons the ester has, the lower the water solubility becomes, and the higher the partition coefficient (ratio between lipid and water solubilities) becomes. If the partition coefficient is high, then at any moment a high proportion of the prodrug is dissolved in oil or body fat, and only a small proportion is dissolved in water.

This is important. If testosterone itself is given in oil solution, it transfers too easily from oil to the water in the blood. The result is that an oil injection of testosterone gives a sudden spike in testosterone levels , which rapidly drops. Injections would be required at least twice per day, and perhaps even more often. Improving the oil solubility and decreasing the water solubility slows this transfer, and extends the half-life of the drug to several days or more.

The number of carbons also has a small effect in that it reduces the parent drug’s proportion of the total weight. E.g., it would take 344 mg of testosterone propionate, or 401 mg of testosterone enanthate to give the same amount of testosterone as in 288 mg of testosterone suspension.

How can the greatly higher anabolic effects of the long chain esters be explained?

While the authors do not make note of it in either article cited, there is a simple explanation for the observed result. Long chain esters of anabolic steroids are not many more times potent than short chain, if indeed they are any more potent at all. Yet in the above study, the undecanoate ester was found to give 3.5 times the effect of the propionate ester. Why?

There is a difference in pharmacokinetics (the time course of the drug in the body). Although the same 1 mg dose is being given in each case, it is either present in the serum of the animal at a relatively high concentration for a relatively short time for the shorter chain esters, or at lower concentration for a longer time for the longer chain esters. This difference can be quite large: the undecanoate ester can be predicted to have a half-life 36 times longer than that of the propionate ester.3

With most drugs, response is not proportional to the dose, but to the log of the dose. Assuming that the dose is well into the effective range, taking ¼ the dose does not result in only ¼ the result, but in ½ the result.
Viewed in this light, if the nandrolone propionate had been given in 36 divided doses over the same length of time that nandrolone undecanoate was in the system, in a manner to match its pharmacokinetics, one would expect 1/6 the result from each individual dose before accounting for molecular weight differences. The cumulative response would be 36 times 1/6, or six times the observed result from the single large dose. If we then correct for the lower molecular weight of the propionate ester, which delivers more nandrolone per mg. than does the undecanoate ester, we would predict 3.3 times more response than from the single large dose. In fact the observed response of the undecanoate ester was 3.5 times that of the propionate ester. This difference is within experimental error.
This calculation I have performed is also supported by experimental evidence performed by van der Vies4. His research showed that when the dose of nandrolone was divided into frequent small injections in such a pattern as to mimic the pharmacokinetics of esters, the anabolic effect became identical to that of the esters.

Thus, pharmacokinetics, the log dose/response curve, and differences in molecular weight are sufficient to account for observed differences in anabolic effect between different esters of an anabolic steroid , or between an ester and the parent drug.

This correlates with my observation that anabolic effect of testosterone esters is equal, so long as each is administered reasonably frequently: at least once per half-life, and preferably twice. E.g., if testosterone propionate yielding some given amount of testosterone per week is administered daily, or at least every other day, it will give results comparable to testosterone cypionate administered at least once every week, and preferably twice per week, that yields the same amount of testosterone per week.

[AnabolicAndre]

Biiiiiizzzump Jayhova if you find your way into this thread I'd like to know how it worked out for you!!!