Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.
PMID 3793856 3793856 DOI 10.1210/jcem-64-2-391 10.1210/jcem-64-2-391 Prior et al. 1987, Prior 1987
Cite this article
Prior, J. C., Cox, T. A., Fairholm, D., Kostashuk, E., & Nugent, R. (1987). Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. The Journal of clinical endocrinology and metabolism, 64(2), 391-394. https://doi.org/10.1210/jcem-64-2-391
Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab. 1987;64(2):391-394. doi:10.1210/jcem-64-2-391
Prior, J. C., et al. "Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen." The Journal of clinical endocrinology and metabolism, vol. 64, no. 2, 1987, pp. 391-394.
Boyle P et al., 2024·Frontiers in Reproductive Health
Low serum estradiol in early pregnancy is associated with an elevated risk of miscarriage. We sought to determine whether efforts to restore low blood estradiol via estradiol or dehydroepiandrosterone (DHEA) supplementation would reduce the risk of miscarriage as part of a multifactorial symptom-based treatment protocol. This retrospective cohort study included women with low serum estradiol levels in early pregnancy, defined as ≤50% of reference levels by gestational age. Estradiol or DHEA were administered orally, and the primary outcome measure was serum estradiol level, in reference to gestational age. The secondary outcome measures included miscarriage, birth weight, and gestational age at birth. We found no significant effect of estradiol supplementation on serum estradiol levels referenced to gestational age, while DHEA supplementation strongly increased estradiol levels. For pregnancies with low estradiol, the miscarriage rate in the non-supplemented group was 45.5%, while miscarriage rate in the estradiol and DHEA supplemented groups were 21.2% (p = 0.067) and 17.5% (p = 0.038), respectively. Birth weight, size, gestational age, and preterm deliveries were not significantly different. No sexual abnormalities were reported in children (n = 29) of DHEA-supplemented patients after 5-7 years follow-up. In conclusion, DHEA supplementation restored serum estradiol levels, and when included in the treatment protocol, there was a statistically significant reduction in miscarriage.
Rossi SP et al., 2023·Molecular and cellular endocrinology
Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide structural support and nutrition to germ cells, we evaluated the effect of melatonin on oxidative state and lactate metabolism in the immature murine TM4 cell line and in immature hamster Sertoli cells. A prooxidant stimulus applied to rodent Sertoli cells expressing MT1/MT2 receptors, increased lipid peroxidation whereas decreased antioxidant enzymes (superoxide dismutase 1, catalase, peroxiredoxin 1) expression and catalase activity. These changes were prevented by melatonin. Furthermore, melatonin stimulated lactate dehydrogenase (LDH) expression/activity via melatonin receptors, and increased intracellular lactate production in rodent Sertoli cells. Interestingly, oral melatonin supplementation in infertile men positively regulated LDHA testicular mRNA expression. Overall, our work provides insights into the potential benefits of melatonin on Sertoli cells contributing to testicular development and the future establishment of a sustainable spermatogenesis.
Lincoff AM et al., 2023·The New England journal of medicine
The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).
Yin WW et al., 2022·BMC Endocr Disord·
Open Access
The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.