A case study describes a morbidly obese infertile man, who after a similar treatment with anastrozole showed a normalized pituitary-testis axis, spermatogenesis and fertility . Finally, the decreased levels of estradiol may have affected the expected rise in lean body mass . A small, controlled study demonstrated that anastrozole in a dose of 1 mg daily during 12 weeks will result in doubling of the mean bioavailable testosterone level in older men . Therefore aromatase inhibitors have been tested in older men suffering from so-called late-onset hypogonadism or partial androgen deficiency. Due to their mode of action the use of aromatase inhibitors is limited to men with at least some residual function of the hypothalamo-pituitary-gonadal axis.
Breast cancer treatments can initiate sterility, menopause, and worsen menopausal symptoms. There were no neurologic or cardiac complications from the chemotherapy. Response to therapy was determined by change in tumor volume. Aromatase inhibitors are not effective for the treatment of gynecomastia in pubertal boys and have limited efficacy for the prevention of gynecomastia in bicalutamide-treated men with prostate cancer. The same group of investigators concluded that there were no effects of letrozole on cognitive performance could be detected in a group of prepubertal boys .
As gynecomastia in men presumably results from an imbalance between androgen and estrogen action, aromatase inhibition was tested as a treatment for gynecomastia in boys. It is well known that aromatase inhibition results in a dramatic reduction of tumor estrogen concentrations . This combination treatment effectively increased growth velocity but epiphysial maturation was slower in the letrozole-treated group, leading to a significant increase in predicted adult height 64,65.
After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Although most of the recent studies with aromatase inhibitors in boys and adult men do not show major detrimental effects on bone long-term skeletal safety remains an issue of concern. Although aromatase inhibitors increase FSH levels, there is no consistent evidence for a beneficial effect on spermatogenesis.
In addition, the patient continued intravenous trastuzumab injections at 3-week intervals for a total of 12 cycles. The patient did refuse her sixth and final dose of docetaxel due to anorexia and malaise, but did agree to take the other three chemotherapeutic agents. The patient was very compliant with the whole food, low-glycemic diet she was instructed to follow. Three, 60 mg T + 4 mg letrozole implants (T + L) were placed in the subcutaneous tissue of the gluteal area under local anesthesia using a disposable trocar kit. Before each insertion procedure, the patient signed a separate consent, which included a description of the benefits, risks, and "off-label" use of the T + AI implants. The right breast mass revealed a (stage 2) grade 3, Estrogen receptor-positive, Progesterone receptor-positive, Human epidermal growth factor receptor 2-positive, KI67 60%, infiltrating ductal carcinoma. Ultrasound revealed a 3.3 × 3.0 cm right breast mass at the 1 o’clock position.
However, the clinical implications for prevention and therapy of cancer, along with reduction of side effects from cancer therapies, could conceivably make an impact on the staggering cost of health care in the United States.38 Because of the lack of adverse drug events from T + L therapy and the beneficial effect on quality of life, this therapy may be an option for patients who are not candidates for cytotoxic chemotherapy, possibly in combination with trastuzumab. Neurotoxicity and cardiac toxicity are possible side effects of this patient's chemotherapy regimen. Regardless, after five cycles of chemotherapy, the tumor was no longer palpable on clinical examination and unable to be identified on ultrasound, that is, complete clinical response. Preclinical evidence supports that T may protect against chemotherapy-induced toxicities without interfering with antitumor activity.14-16 However, the effect of subcutaneous T + AI on chemotherapeutic response had not been previously studied in humans.
Nevertheless, the objective findings do suggest a testable hypothesis and likely valid conclusions, which may eventually affect 12.4% of the female population diagnosed with breast cancer. Nevertheless, subcutaneous delivery of an AI is not "standard of care." However, the 8 mg dose of subcutaneous letrozole maintained serum E2 levels below 5 pg/mL, which is the target level of E2 used in comparative (efficacy) studies on oral AIs.20 We know that this patient's tumor did respond favorably to T + L therapy. However, previous case reports and two of the authors’ (RG, CD) clinical experience (unpublished data) have demonstrated similar tumor responses to T + AI combination implant therapy in the neoadjuvant setting.3 T is the major substrate for E2 in postmenopausal patients and has a stimulatory effect via the estrogen receptor. T + AI, testosterone-aromatase inhibitor.aThere was no charge for this patient. The patient's weight remained stable throughout chemotherapy (67.7 ± 0.72 kg).
Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. In older men with so-called late-onset hypogonadism, aromatase inhibitors may emerge as an attractive alternative for traditional testosterone supplementation to improve testosterone levels. Furthermore, hyperandrogenism induced by treatment with aromatase inhibitors may result in decreased HDL-cholesterol and increased hemoglobin levels , indicating the need for follow-up during treatment.

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