methimazole and Infertility--Male

To understand the mechanism underlying gestational-onset hypothyroidism-induced male infertility.. Controlled laboratory study.. Research laboratory in a university department of endocrinology.. Wistar rat.. Pregnant rats were exposed to methimazole from embryonic days 9 to 14, 18, and 21, covering specific fetal periods of differentiation and development of male reproductive tract organs.. Fertility of male rats was assessed by testing sperm count, forward motility, and in vivo fertilizing ability. Secretory activity of the epididymis was evaluated by quantifying sialic acid, carnitine, and glycerylphosphorylcholine. Bioavailability of androgens was assessed by quantifying testosterone in serum and testicular interstitial fluid and epididymal 5alpha-reductase activity/mRNA expression. Androgen receptor (AR) status in the epididymis was tested by detecting the expression levels of its mRNA and protein, as well as ligand binding activity. Data were analyzed statistically by one-way analysis of variance.. Gestational exposure to methimazole decreased sperm forward motility, in vivo fertilizing ability, bioavailability of androgens, AR status, and secretory activity of the epididymis in adult rats.. Transient gestational-onset hypothyroidism affects male fertility by impairing posttesticular sperm maturation process in the epididymis, owing to subnormal androgen(s) bioavailability, AR expression, and AR functional activity.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Animals; Epididymis; Female; Hypothyroidism; Infertility, Male; Male; Methimazole; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptors, Androgen; RNA, Messenger; Sperm Maturation; Sperm Motility; Testis; Thyroid Hormones

To present a case of primary male infertility with severe oligospermia and hyperpigmented skin as the main presenting clinical signs.. Case report.. University-affiliated teaching hospital.. A 32-year-old male with severe oligospermia and his 31-year-old female partner with normal cycles.. Hydrocortisone, fludrocortisone, methimazole, and eventual IVF.. Improved semen analysis, correction of Addison's disease, correction of hyperthyroidism, and ART pregnancy.. Severe oligospermia of 5 million per milliliter with 15% motility and ACTH level of 2,800 pg/mL on presentation. Endocrinology evaluation revealed cortisol of <0.1 microg/dL, and Cortrosyn test showed no response (Addison's disease). The patient was incidentally found to have a thyroid stimulating hormone level of <0.1 microIU/mL, T4 of 9.5 microg/dL, Free T4 Index calculation of 11.6 microg/dL, and quantitative triiodothyronine of 273 ng/dL on presentation. His Addison's disease was managed with hydrocortisone and fludrocortisone, and his hyperthyroidism, with methimazole. Semen parameters increased to 34 million per milliliter with 45% motility and 5% Kruger morphology 1 year after initial presentation. Hormone parameters normalized. Rather than allowing for more time for natural conception or IUI, the couple decided to proceed with IVF because of insurance coverage before semen parameters normalized.. This is the first reported case of Addison's disease presenting as male infertility with hyperpigmentation of the skin being the only other presenting sign. The underlying etiology of the Addison's in this case remains uncertain, but it is presumed because of autoimmunity. Addison's disease may be associated with hyperthyroidism, and hyperthyroidism may have contributed to the oligospermia. This case highlights why men with abnormal semen parameters should be thoroughly evaluated before proceeding with assisted reproduction.

Topics: Addison Disease; Adult; Diagnosis, Differential; Humans; Infertility, Male; Male; Methimazole