Case Challenges

Treating a patient with gynecomastia

A 49-year-old Hispanic man was referred to me by his primary care physician for evaluation of gynecomastia. He had first noticed symmetrically increased breast size at the age of 15 and felt depressed and socially stigmatized because of it. He had also noticed increased growth two years ago, but none lately. The patient stated that he had good libido and no erectile dysfunction. He denied galactorrhea or bloody discharge from his nipples. He also denied breast pain or lumps.

Other medical history consisted of depression, recently diagnosed bipolar disorder and a remote history of left tibia fracture. Medications included bruproprian hydrocholride (Wellbutrin, GlaxoSmithKline), naproxen and lamotrigine (Lamictal, GlaxoSmithKline), which had only been started six months prior. He was not ingesting any nutritional supplements or over-the-counter medications.

Ronald Tamler, MD, PhD, MBA
Ronald Tamler

The patient had been living at a drug rehab facility with other young men due to a previous cocaine addiction, and he was being teased for his pendulant breasts (this significantly worsened his psychiatric ailments). He was no longer using drugs, smoked five cigarettes a day and denied alcohol use.

Physical exam was remarkable for depressed-appearing middle-aged man with pendulant symmetric breasts and true gynecomastia (ie, breast tissue was palpable). He is 5 ft 6 in, 196 lb, and had normal blood pressure and heart rate. Normal male hair growth and distribution, urogenital exam remarkable for testicular size on the small side of normal (approximately 13 cc to 15 cc bilaterally).

The patient’s total testosterone was normal at 505 ng/dL, free T low-normal at 8 ng/dL, Estradiol high at 40 pg/mL. Luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, free T 4, dehydroepiandrosterone, human chorionic gonadotropin and chemistry profile with liver values were normal.

49-year-old Hispanic man referred for evaluation of gynecomastia.
49-year-old Hispanic man referred for evaluation of gynecomastia.

Source: Ronald Tamler

What is the best way to manage this patient’s gynecomastia?

  1. Walk him over to the radiology department and have him get a mammography on the spot.
  2. Refer him to a plastic surgeon for bilateral subcutaneous mastectomy and explain that insurance ordinarily will not cover the cost of the surgery.
  3. Prescribe raloxifene (Evista, Lilly) 60 mg daily or tamoxifen 20 mg daily.
  4. Prescribe anastrozole (Arimidex, AstraZeneca) 1 mg daily.
  5. Send him back to the primary care physician and explain that he will have to live with his gynecomastia.

CASE DISCUSSION

The answer is B. This patient has gynecomastia. It is very common and affects about half of the male population, demonstrating increasing prevalence with age and transiently affecting the majority of boys in puberty. An imbalance between free estradiol and testosterone is at the core of this condition. Any condition that will favor the effects of estrogen over androgen has the potential of inducing gynecomastia. Reasons include:

  • Absolute overproduction of estrogen, be it from a testicular or an adrenal tumor, an human chorionic gonadotropin-producing tumor (leading to increased estrogen production), or increased aromatization of testosterone-to-estrogen. This last process happens in obesity and familial aromatase excess syndrome.
  • Absolute deficiency of testosterone, as is found in certain hypogonadal states and patients treated with hormone deprivation therapy for prostate cancer. An unresponsive androgen receptor will have the same effect.
  • Increased sex hormone-binding globulin levels, with rising sex hormone-binding globulin preferably binding testosterone, thus decreasing the free testosterone to estrogen ratio. This process is thought to be at the heart of gynecomastia of aging as well as with thyrotoxicosis.
  • Chronic renal and liver disease (probably related to hypogonadism and elimination of estrogen). Certain pharmacological and recreational drugs altering the testosterone-to-estrogen ratio.

Common sense dictates that if a culprit for this imbalance is found, appropriate treatment has the greatest chance of improving gynecomastia. However, there may not always be a clear-cut cause. Since decreased testosterone to estrogen balance is at the center of this problem, any action that will increase testosterone action or decrease estrogen action at the respective receptor has a chance of success. Blocking the conversion of testosterone-to-estrogen with an aromatase inhibitor such as anastrozole (option D) would be such a strategy.

However, we now know that estradiol plays a significant role for bone health in men, and blocking the conversion could thus lead to osteopenia or even osteoporosis over time. This is less likely to happen with selective estrogen receptor modulators, such as raloxifene or tamoxifen (option C ). Indeed, reasonable results have been reported with both agents, but never for a study period longer than three months.

Although it has been reported that 1% of all breast cancers are found in men, not every man with gynecomastia requires a mammography. Families with Klinefelter’s syndrome (XXY carrier) or mutations in the autosomal-dominant BRCA2 gene have a higher incidence, and the average age is 71 years. One would typically expect a painless lump, and possibly bloody discharge from the nipple. Therefore, this patient did not require further evaluation for possible malignancy (option A).

In this case, gynecomastia had persisted for more than a year, making it less susceptible to medical treatment. Therefore, I referred the patient to a plastic surgeon for bilateral mastectomy. Insurance typically does not cover the procedure, but our plastic surgery residency program waived the cost for this severely afflicted patient. I also learned something interesting along the way: Surgeons prefer that the patient does not smoke or use vasoconstrictive agents (such as cocaine) to optimally support the healing process.

As for option (E): Many patients can indeed be comforted with the information that so many other men have a similar condition. However, when the problem becomes so vexing that it creates or worsens psychiatric problems or social isolation, treatment options need to be offered. I will never forget the patient’s gratitude when I told him that I would refer him to surgery.

Ronald Tamler, MD, PhD, is an Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine.

A 49-year-old Hispanic man was referred to me by his primary care physician for evaluation of gynecomastia. He had first noticed symmetrically increased breast size at the age of 15 and felt depressed and socially stigmatized because of it. He had also noticed increased growth two years ago, but none lately. The patient stated that he had good libido and no erectile dysfunction. He denied galactorrhea or bloody discharge from his nipples. He also denied breast pain or lumps.

Other medical history consisted of depression, recently diagnosed bipolar disorder and a remote history of left tibia fracture. Medications included bruproprian hydrocholride (Wellbutrin, GlaxoSmithKline), naproxen and lamotrigine (Lamictal, GlaxoSmithKline), which had only been started six months prior. He was not ingesting any nutritional supplements or over-the-counter medications.

Ronald Tamler, MD, PhD, MBA
Ronald Tamler

The patient had been living at a drug rehab facility with other young men due to a previous cocaine addiction, and he was being teased for his pendulant breasts (this significantly worsened his psychiatric ailments). He was no longer using drugs, smoked five cigarettes a day and denied alcohol use.

Physical exam was remarkable for depressed-appearing middle-aged man with pendulant symmetric breasts and true gynecomastia (ie, breast tissue was palpable). He is 5 ft 6 in, 196 lb, and had normal blood pressure and heart rate. Normal male hair growth and distribution, urogenital exam remarkable for testicular size on the small side of normal (approximately 13 cc to 15 cc bilaterally).

The patient’s total testosterone was normal at 505 ng/dL, free T low-normal at 8 ng/dL, Estradiol high at 40 pg/mL. Luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, free T 4, dehydroepiandrosterone, human chorionic gonadotropin and chemistry profile with liver values were normal.

49-year-old Hispanic man referred for evaluation of gynecomastia.
49-year-old Hispanic man referred for evaluation of gynecomastia.

Source: Ronald Tamler

What is the best way to manage this patient’s gynecomastia?

  1. Walk him over to the radiology department and have him get a mammography on the spot.
  2. Refer him to a plastic surgeon for bilateral subcutaneous mastectomy and explain that insurance ordinarily will not cover the cost of the surgery.
  3. Prescribe raloxifene (Evista, Lilly) 60 mg daily or tamoxifen 20 mg daily.
  4. Prescribe anastrozole (Arimidex, AstraZeneca) 1 mg daily.
  5. Send him back to the primary care physician and explain that he will have to live with his gynecomastia.

CASE DISCUSSION

The answer is B. This patient has gynecomastia. It is very common and affects about half of the male population, demonstrating increasing prevalence with age and transiently affecting the majority of boys in puberty. An imbalance between free estradiol and testosterone is at the core of this condition. Any condition that will favor the effects of estrogen over androgen has the potential of inducing gynecomastia. Reasons include:

  • Absolute overproduction of estrogen, be it from a testicular or an adrenal tumor, an human chorionic gonadotropin-producing tumor (leading to increased estrogen production), or increased aromatization of testosterone-to-estrogen. This last process happens in obesity and familial aromatase excess syndrome.
  • Absolute deficiency of testosterone, as is found in certain hypogonadal states and patients treated with hormone deprivation therapy for prostate cancer. An unresponsive androgen receptor will have the same effect.
  • Increased sex hormone-binding globulin levels, with rising sex hormone-binding globulin preferably binding testosterone, thus decreasing the free testosterone to estrogen ratio. This process is thought to be at the heart of gynecomastia of aging as well as with thyrotoxicosis.
  • Chronic renal and liver disease (probably related to hypogonadism and elimination of estrogen). Certain pharmacological and recreational drugs altering the testosterone-to-estrogen ratio.

Common sense dictates that if a culprit for this imbalance is found, appropriate treatment has the greatest chance of improving gynecomastia. However, there may not always be a clear-cut cause. Since decreased testosterone to estrogen balance is at the center of this problem, any action that will increase testosterone action or decrease estrogen action at the respective receptor has a chance of success. Blocking the conversion of testosterone-to-estrogen with an aromatase inhibitor such as anastrozole (option D) would be such a strategy.

However, we now know that estradiol plays a significant role for bone health in men, and blocking the conversion could thus lead to osteopenia or even osteoporosis over time. This is less likely to happen with selective estrogen receptor modulators, such as raloxifene or tamoxifen (option C ). Indeed, reasonable results have been reported with both agents, but never for a study period longer than three months.

Although it has been reported that 1% of all breast cancers are found in men, not every man with gynecomastia requires a mammography. Families with Klinefelter’s syndrome (XXY carrier) or mutations in the autosomal-dominant BRCA2 gene have a higher incidence, and the average age is 71 years. One would typically expect a painless lump, and possibly bloody discharge from the nipple. Therefore, this patient did not require further evaluation for possible malignancy (option A).

In this case, gynecomastia had persisted for more than a year, making it less susceptible to medical treatment. Therefore, I referred the patient to a plastic surgeon for bilateral mastectomy. Insurance typically does not cover the procedure, but our plastic surgery residency program waived the cost for this severely afflicted patient. I also learned something interesting along the way: Surgeons prefer that the patient does not smoke or use vasoconstrictive agents (such as cocaine) to optimally support the healing process.

As for option (E): Many patients can indeed be comforted with the information that so many other men have a similar condition. However, when the problem becomes so vexing that it creates or worsens psychiatric problems or social isolation, treatment options need to be offered. I will never forget the patient’s gratitude when I told him that I would refer him to surgery.

Ronald Tamler, MD, PhD, is an Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine.