Gynecomastia: Causes, Symptoms, and Treatment

Gynecomastia is a medical condition characterized by the development of enlarged breast tissue in males. While not typically harmful, it can cause physical discomfort and emotional distress. Let’s delve into the details of gynecomastia, including its causes, symptoms, and available treatment options.

Testosterone for Women

Women accurately diagnosed with hypoactive sexual desire dysfunction (HSDD) and female sexual arousal disorder (FSAD) may benefit from testosterone supplementation. Testosterone therapy appears to be helpful and safe when the dose does not exceed premenopausal physiological levels.

High natural testosterone production in men is associated with blood clots and heart disease

Analysis of two major Mendelian randomization studies revealed that endogenous testosterone production in men is positively correlated with blood clots, heart attack, and heart failure. Data from at least 200,000 participants were included in the analysis. A proposed mechanism for such a risk is the testosterone conversion into estrogen, in turn contributing to thromboembolism. Testosterone can also increase platelet aggregation via the thromboxane A2 pathway.

Data from these “natural experiments” overall follow the observed increased risk of deep venous thrombosis and heart disease in men who are over-supplemented with exogenous testosterone. On the contrary, low Testosterone levels are also associated with visceral adiposity, low muscle mass, and insulin resistance.  From a cardiovascular perspective, future clinical research is needed to identify the balancing point of how much or little testosterone men should have.


New FDA approval: oral testosterone

In March 2019 FDA approved the first oral testosterone supplementation for male patients with documented central (primary) or peripheral (secondary) hypogonadism. The medication is given twice a day orally. The recommended starting dose is about 250 mg every 12 hours. The minimum dose is about 150 mg BID with a maximum dose of 400 mg BID.

Follow up blood work needs to be done at least 7 days after initiation and 6 hours after the morning dose. Side effects may include elevated blood pressure, increased red blood cell mass, prostate enlargement, and GI upset. The approval comes with a black box warning for increased risk of hypertension and cardiovascular events.


New FDA Approval: Subcutaneous Testosterone Pen

The FDA has now approved the first subcutaneous testosterone auto-injector pen (Xyosted) for symptomatic patients with low testosterone levels. It is self-administered once weekly and is available in three doses: 50 mg, 75 mg, and 100 mg. The recommended starting dose is 75 mg per week.

2018 Testosterone Therapy Guidelines

This is an update of previous guidelines published in 2010.

We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and involving the patient in decision making. 

We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations.

Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.


Intramuscular testosterone injection

Patients with low testosterone levels could have decreased libido, erections and stamina. They could also suffer from reduced bone mass, muscle mass, and physical capacity. Intramuscular testosterone injection is an efficient and safe way to help patients with testosterone deficiency. The following video shows how to self-administer the testosterone injection.


Sexual function after bariatric surgery

This meta-analysis shows that bariatric surgery significantly improves sexual function in men but that a more limited degree of improvement is achieved in women.

In obese male patients who underwent bariatric surgery, the levels of the sex hormones TT, FT, LH, FSH, and SHBG significantly increased, and the level of E2 decreased. In obese female patients, the levels of the sex hormones TT, FT, and E2 decreased, but the levels of LH, FSH, and SHBG increased.

Future studies should be performed to elucidate the mechanism of the improved sexual function in obese patients after bariatric surgery. 


New FDA approval: intrarosa helps with pain during sex

DHEA is the main testosterone-like substance produced by the adrenal glands. Naturally it declines with age. Once a day vaginal insert of DHEA (intrarosa or prasterone) helps postmenopausal women experience less pain during intercourse. Side effects include abnormal pap smear and vaginal discharge. Currently there is no evidence that over-the-counter oral DHEA supplementation helps with such symptoms.


Subcutaneous testosterone injections

Intramuscular testosterone injection is the most common form of androgen supplementation in hypogonadal men.

A group of 11 participants undergoing female-to-male gender transition were analyzed. Findings reveal that weekly subcutaneous testosterone (cypionate/ester) injections work well clinically.  Total and free testosterone measures were overall stable and not influenced by body mass index. 

Superiority of subcutaneous over intramuscular injections relies on improved convenience, safety, and cost. Approximately 25% lower SC than IM dose of testosterone is needed to achieve similar outcomes.

A strength of the study was the female genetic background (XY); contributing trivial amounts of endogenous testosterone to steady serum total and free measures. Alike results would be expected in hypogonadal men requiring androgen supplementation.

These findings could influence clinical practice, as the prevalence of male hypogonadism is significant.


Laboratory interference gives false results on various hormone measures

An important case pointing to the endocrinologist’s dilemma when facing inappropriate or discordant hormonal results. This patient had severely high levels of serum estradiol, progesterone, testosterone, and cortisol in complete absence of clinical signs and symptoms.

Mass spectrometry, an expensive and poorly available analytical technique, saved the day. Mild monoclonal IgG elevation (hypergammaglobulinemia) was felt to be the interfering agent leading to falsely high hormone measures. Interference could also occur in the setting of heterophilic antibodies, rheumatoid factor and biotin intake, none which were present in this case.

Important to be aware of false deviations in blood work, as inability to realize it could generate unnecessary anxiety, testing, imaging, procedures and even intervention.


Ovarian Suppression by Elagolix

This study elucidates kinetic and dynamic properties of elagolix, an oral GnRH antagonist. Authors find that elagolix suppresses LH/FSH and Estradiol/Progestorone fully at respective doses of 300 mg and 200 mg BID. As expected the main side effects were hot flashes and headaches (induced menopausal symptoms). A group of 45 healthy premenopausal women were followed for 21 days.

Estrogen/ovarian suppression is needed in certain medical conditions such as hormone-dependent breast carcinomas.