We have previously shown that LHRH agonist [D-Trp6,Pro9-NEt]LHRH (LHRHA) results in reversible oligozoospermia when given to normal subjects for up to ten weeks. A fall in plasma testosterone was accompanied by loss of libido and potency. We now report six subjects who were evaluated by semen analysis and hormone profile at two-week intervals during ten-week basal, 20-week treatment, and post-treatment periods lasting at least ten weeks. Treatment consisted of LHRHA (50 microgram subcutaneously daily), and testosterone enanthate (100 mg intramuscularly every two weeks). Sperm density (mean basal 76.7 +/- 8.7 x 10(6)/ml) fell consistently in each subject to a mean nadir of 12.3 +/- 4.5 x 10(6)/ml (p less than 0.001). This is similar to the mean nadir of 11.6 +/- 5.8 x 10(6)/ml achieved when LHRHA was given alone. In each individual subject, sperm density returned to his basal level after cessation of treatment. No consistent changes were seen in sperm motility of morphology, or in semen volume. Libido and potency were maintained in all subjects. An additional three subjects received testosterone enanthate alone in identical dosage for 20 weeks. No change in sperm density was observed. In contrast to treatment with LHRHA alone, combination treatment produces reversible oligozoospermia without attendant change in potency.

Atherosclerosis is a polygenic disorder that often affects multiple arteries. Carotid arteries are common sites for evaluating subclinical atherosclerosis, and aortic root is the standard site for quantifying atherosclerosis in mice. We compared genetic control of atherosclerosis between the two sites in the same cohort derived from two phenotypically divergent Apoe-null (Apoe-/-) mouse strains. Female F2 mice were generated from C57BL/6 (B6) and C3H/He (C3H) Apoe-/- mice and fed 12 weeks of Western diet. Atherosclerotic lesions in carotid bifurcation and aortic root and plasma levels of fasting lipids and glucose were measured. 153 genetic markers across the genome were typed. All F2 mice developed aortic atherosclerosis, while 1/5 formed no or little carotid lesions. Genome-wide scans revealed 3 significant loci on chromosome (Chr) 1, Chr15, 6 suggestive loci for aortic atherosclerosis, 2 significant loci on Chr6, Chr12, and 6 suggestive loci for carotid atherosclerosis. Only 2 loci for aortic lesions showed colocalization with loci for carotid lesions. Carotid lesion sizes were moderately correlated with aortic lesion sizes (r=0.303; p=4.6E-6), but they showed slight or no association with plasma HDL, non-HDL cholesterol, triglyceride, or glucose levels among F2 mice. Bioinformatics analyses prioritized Cryge as a likely causal gene for Ath30, Cdh6 and Dnah5 as causal genes for Ath22. Our data demonstrate vascular site-specific effects of genetic factors on atherosclerosis in the same animals and highlight the need to extend studies of atherosclerosis to sites beyond aortas of mice.

The agonist analogue of gonadotropin-releasing hormone (GnRH), [(imBz1)-D-His6,Pro9-NEt]GnRH, has a potency 200 times that of the native hormone in vitro. In single dose studies in man, this analogue resulted in 2- to 4-fold elevation of LH and FSH, and demonstrated a prolonged duration of activity. [(imBz1)-D-His6,Pro9-NEt]GnRH appears to be safe and, as with other analogues of GnRH, may have application to clinical medicine.

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