[Mulletsoldier]

Now, without viewing you, speaking to you, or hearing any of your symptoms, I can (statistically speaking) assure you that you do not have Gynecomastia. The frequency of post-pubertal Gynecomastia is estimated to be less than 10% of the male population; approximately 50% of pubertal boys may experience some form of Gynecomastia.

Further, a very small amount of physician-approached, post-pubertal, clinically defined Gynecomastia is drug induced. So, more than likely, you do not have 'Gyno', as it is known on the boards.

This begs the question, however: what is Gynecomastia? This thread is going to address that question, address the corollary "what is not Gynecomastia", as well as reviewing pertinent treatments of the affliction.

Table of Contents:

I. What is Gynecomastia
II. What is Not Gynecomastia
III. Popular and Proven Treatments

I. What is Gynecomastia

Clinically defined Gynecomastia is a benign enlargement of the mammary gland component of the male breast; the extreme proliferation of glandular tissue must occur to be clinical Gynecomastia. Most often, this proliferation is accompanied by pectoral adipose tissue, but the conditions are not mutually inclusive. Note: I will repeat this many times throughout this thread, without glandular tissue, it is not Gynecomastia. While Gynecomastia is most often unilateral, it can be bilateral as well.

From: Gynecomastia

Types of Gynecomastia:

Type I: Benign adolescent hypertrophy
Physiologic discoid subacute mass
Resolves spontaneously
Type II: Physiologic gynecomastia - Generalized enlargement to greater degree
Type III: Obesity simulates gynecomastia
Type IV: Pectoral muscle hypertrophy

Marshall & Tanner Stages of breast enlargement/ development
[Adapted from Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969: 44:2291-303.]
Stage 1: Preadolescent; only papillae are elevated.
Stage 2: Breast bud and papilla are elevated and a small mount is present; areola diameter is enlarged.
Stage 3: Further enlargement of breast mound; increased palpable glandular tissue.
Stage 4: Areola and papilla are elevated to form a second mound above the level of the rest of the breast.
Stage 5: Adult mature breast; recession of areola to the mound of breast tissue, rounding of the breast mound, and projection of only the papilla are evident.

Causes

The causes of Gynecomastia in its three most often experienced stages - infancy, adolescence, and the elderly - are rarely identified on a case-by-case basis. However, in respects to the current audience, the use of a wide-range of hormonal compounds can cause the enlargement of the glandular component of the male breast.

While an in-depth discussion of hormonal feedback loops, and ER/PR receptor and receptor subtype expression is a far too robust discussion for this thread, it is needless to say hormones are not tinker toys - that is, removing and/or introducing and/or modifying one (or one set) of hormones most likely will remove and/or introduce and/or modify your existing hormones. Such hormonal fluctuations can cause a new case, or exacerbate and existing case, of Gynecomastia.

Diagnosis

Here is where I repeat the take-home lesson from this thread: without glandular proliferation (i.e., enlargement of the mammary gland) it is not Gynecomastia.

In order to ascertain whether or not you have Gynecomastia, there are three major procedures to conduct:

1) Conduct a self-breast examination - note their overall consistency and shape. Conduct the examination in front of a mirror in order to gain a perspective of the chest as a whole. True Gynecomastia will be characterized by an altered morphology of the chest; such a condition is not an "I wonder" condition. If you have it, you will notice. If your breast size is greater than 5cm (macromastia, or 'large breast) you most likely have physiologic, or pathologic Gynecomastia.

2) Lie flat on your back, and place one thumb on either side of the nipple. Slowly bring your thumbs together, applying pressure inwards to the chest. If you have Gynecomastia, your thumbs will press against hard, fibrous, and rubbery glandular tissue; if you do not, your thumbs will meet at the nipple. If fibrous tissue is noted, it should be very tender, and painful to the touch.

3) While this can be conducted with number one, a separate test should be conducted to note for oily discharge from the nipple. If Gynecomastia is present, the discharge should be easily excreted; the constant aggravation of breast tissue may produce discharge even in pseudogynocomastia (if it does not come on first squeeze, stop touching it).

If you not either of these indicative symptoms, you may have Gynecomastia, and at which point you should contact a physician for referral; if you did not note either of these symptoms, continue onto the next section.

Physical Documentation of True Gynecomastia:





I am sure your most immediate reaction to this picture is, "That looks nothing like me!". While this patient is obese, true Gynecomastia has a very similar morphology, merely on a smaller scale.

II. What is Not Gynecomastia

Now that we have ascertained what Gynecomastia is, we must now differentiate what is not.

Conditions Which Are Not Gynecomastia

1) 'Puffy' or 'sensitive' nipples. If you note a very slight inflammation and tenderness to your nipples while using hormonal products, do not be alarmed. It is very possible estrogen has become bound to ERs under your nipples, but this is not necessarily Gynecomastia. A mere reduction of circulating estrogen via an AI, or spot-specific treatment via a SERM, will more often than not eradicate such a symptom.

2) The existence of a 'pebble' under or around the nipple. If you detect small fibrous 'pebbles' directly under your nipple, this very well may be the precursor to Gynecomastia. However, at such a time where the 'pebble' is newly developed, minor treatment with an effective SERM or AI will most likely remove the tissue.

3) Excess adipose tissue in and around the pectoral area. Remember: without glandular tissue, it is not Gynecomastia. While adipose tissue most often accompanies Gynecomastia, it is not Gynecomastia in-and-of-itself; such adipose not accompanied by glandular tissue is what is known as, 'pseudogynecomastia'.

Pseudogynecomastia

Pseudogynecomastia is any one, or more of the conditions listed above without the proliferation of glandular tissue. It is most likely caused by the stimulation of estrogen or progesterone receptor or receptor subtypes in the breast area; in most cases, as said earlier, they can be remedied by using systemic or breast-specific estrogen controlling remedies.

III. Popular and Proven Treatments

A quick research search will reveal that invasive surgery is regarded as the only manner to remove permanent glandular tissue; however, recent studies have revealed the use of aromatase inhibitors such as Letrozole, or SERMs such as Tamoxifen Citrate, can eradicate proliferated glandular tissue.

In cases of long or unknown duration, or where macromastia beyond increased glandular tissue is noted, surgery is almost always required. With that being said, most treatment centers and studies noted that tissue under 36 months duration can be treated non-surgically.

The two most common classes of Gynecomastia treatments are SERMs (Selective Estrogen Receptor Modulators) which are breast-specific, and AI (Aromatase Inhibitors) which are systemic, and lower serum levels of E1 and E2.

The most common SERMs are:

Tamoxifen
Raloxifen
Toremifene
Clomid

The most common Aromatase Inhibitors are:

Letrozole
Anastrozole

Literature on several of the above mentioned compounds.

Tamoxifen treatment for pubertal gynecomastia

By Derman O, Kanbur NO, Kutluk T.
Section of Adolescent Medicine, Department of Pediatrics,
Hacettepe University Faculty of Medicine, 06100 Ankara-Turkey.
We evaluated the efficacy of the tamoxifen treatment in 37 patients with pubertal gynecomastia. All had distinct, easily palpable breast swellings with a diameter of over three cm. Pain, tenderness, and swelling associated with gynecomastia were reported by six patients. Eight of the patients were obese. One patient also suffered from varicocele. Pain and size reduction was seen in all patients with tamoxifen treatment. No long-term side effects of tamoxifen were observed. The dose of tamoxifen was increased in three patients due to poor response. Two of the treatment group had recurrence problem at follow-up. We did not need to refer any patient to surgery. Tamoxifen treatment is relatively non-toxic, may be beneficial and we think it should be considered for pubertal gynecomastia.

1: J Pediatr. 2004 Jul;145(1):71-6. Related Articles, Links

Comment in:

* J Pediatr. 2005 Apr;146(4):576; author reply 576-7.
* J Pediatr. 2005 Apr;146(4):576; author reply 576-7.

Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia.

Lawrence SE, Faught KA, Vethamuthu J, Lawson ML.
Department of Pediatrics, University of Ottawa, Ontario, Canada.

OBJECTIVES: To assess the efficacy of the anti-estrogens tamoxifen and raloxifene in the medical management of persistent pubertal gynecomastia.

STUDY DESIGN: Retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia who presented to a pediatric endocrinology clinic. Patients received reassurance alone or a 3- to 9-month course of an estrogen receptor modifier (tamoxifen or raloxifene).

RESULTS: Mean (SD) age of treated subjects was 14.6 (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving raloxifene, but a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients.

CONCLUSION: Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

PMID: 15238910 [PubMed - indexed for MEDLINE]

Treatment of Pubertal Gynecomastia with the Specific Aromatase Inhibitor Anastrozole
Felix G. Riepe, Inka Baus, Stephanie Wiest, Nils Krone, Wolfgang G. Sippell, Carl-Joachim Partsch

Division of Pediatric Endocrinology, Department of Paediatrics, Christian-Albrechts-Universität Kiel, Kiel, Germany

Horm Res 2004;62:113-118 (DOI: 10.1159/000079882)

Abstract

Gynecomastia can be detected in up to 70% of boys during puberty and in about one third of adult males. An imbalance of estrogen to androgen tissue levels is believed to be the major reason for the development of gynecomastia; as a result most medical treatments so far have tried to lower the estrogen level. Five boys with pubertal gynecomastia and breast tenderness were treated for 6 months with the selective aromatase inhibitor anastrozole. Initial plasma levels of estradiol (E2), testosterone (T), androstenedione, dehydroepiandrosterone sulfate (DHEA-S) and gonadotropins were normal. DHEA-S showed a significant rise during treatment. T and androstenedione showed no significant change during treatment. E2 decreased with therapy, although to no statistically significant extent. The E2/T ratio decreased significantly during the treatment. Breast size decreased in 4 out of 5 patients, and in 1 of these 4 boys glandular breast tissue disappeared completely. The longer the duration of gynecomastia before anastrozole administration, the smaller was the reduction of breast size. Breast tenderness was resolved in all boys within 4 weeks. No adverse effects were recorded. Since the aim of medical treatment is the total disappearance of breast tissue, anastrozole, as previous aromatase inhibitors, is of limited effect. However, anastrozole seems to be of benefit for the treatment of tenderness in gynecomastia and for patients in whom surgery is particularly risky. However, as spontaneous disappearance of pubertal gynecomastia is common, further double-blinded, placebo-controlled trials are necessary before a definite conclusion can be drawn about the effectiveness and the side effects of this therapy.

BCS: Femara (Letrozole) Significantly More Effective Than Tamoxifen In Treating Advanced Breast Cancer

"Letrozole was consistently more effective than tamoxifen in the advanced disease setting. It was very satisfying to observe significantly improved outcomes with letrozole in the preoperative trial as well," said Matthew Ellis, MD, Ph.D., FRCP, Clinical Director, Duke Breast Cancer Program, Duke University Medical Center and lead investigator in the pre-operative study. "These data will provide great impetus for the ongoing letrozole adjuvant trials and underscore the potential of letrozole to benefit thousands of postmenopausal women with breast cancer every year."
This study of more than 900 women compared the efficacy of Femara and tamoxifen as first-line treatment for advanced breast cancer. The results demonstrate that Femara delays progression of advanced breast cancer for 9.4 months, as compared to 6.0 months for tamoxifen (41 weeks vs. 26 weeks). Results also indicate significant differences between Femara and tamoxifen with respect to overall tumor response rates (30 percentvs. 20 percent), clinical benefit (49 percent vs. 38 percent) and time to treatment failure (9.1 months vs. 5.7 months, or 40 weeks vs. 25 weeks).
The women enrolled in this phase III randomized, double blind multi-center trial were postmenopausal with either locally advanced (stage IIIB) disease, or metastatic breast cancer, or had recurrences not amenable to treatment with surgery or radiotherapy.
In this phase III randomized, controlled trial of 324 postmenopausal women, patients with large localized or locally advanced breast cancer tumors were given Femara or tamoxifen as pre-operative treatment for four months to reduce tumor size before surgery. The primary objective was to compare the anti-tumor activity of Femara, an aromatase inhibitor, to that of tamoxifen by measuring clinical tumor response in these patients.
Clinical responses in this study were significantly better for Femara than for tamoxifen (55 percent versus 36 percent). After adjustment for tumor size, nodal involvement and age, the odds of undergoing breast-conserving surgery were increased by more than 70 percent for Femara compared with the odds for tamoxifen.

Bicalumatide is an anti-androgen used in the treatment of Prostate Cancer:

1: J Clin Oncol. 2005 Feb 1;23(4):808-15. Links
Comment in:
J Clin Oncol. 2005 Aug 20;23(24):5845: author reply 5846-7.
Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, Comeri G, Bertaccini A, Martorana G, Galassi P, Zattoni F, Macchiarella A, Siragusa A, Muscas G, Durand F, Potenzoni D, Manganelli A, Ferraris V, Montefiore F.
University and National Cancer Research Institute, University of Genoa, Genoa, Italy. f.boccardo@unige.it
PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

Also important to note, again: hormones are not tinker toys. A dose of 2.5mg of Letrozole ED is a very common 'panic dose': it is not a dose reflected in the research, and is not wise. Such a high dose of Letrozole over extended periods can cause serious lipid alteration, as well as severe sexual dysfunction which is not easily corrected.

As other threads have covered such a topic, dosing will not be covered in this particular thread. I hope you have found this resource helpful.

Updated with more data.

[mindgame]

I pray people read this and most of these "gyno" threads wont be any more common. Good thread.

[Mulletsoldier]

I hope and pray that they do - the constant 'GYNO HELP!' threads were my reason for creating this.

[mindgame]

I kinda figured that why you made this.

[Jayhawkk]

Thanks for making it Mullet. Stuck it.

[Mulletsoldier]

Gracias senor!

[edwards]

Nice job. There should be a sticky on it. There will still be plenty of gyno posts, but at least you can point them someplace.

[borobulker]

thank you Dr. Mullet. Nice info.

[EasyEJL]

I used java lather in the shower today, and now my nipples are tender. Do I have gyno from java lather?

[Mulletsoldier]

No problem G.

[Rhyno]

Great read, thanks.

[Mulletsoldier]

Originally Posted by EasyEJL

I used java lather in the shower today, and now my nipples are tender. Do I have gyno from java lather?

Haha, I doubt it.