Hypogonadism in Reproductive Years


  • Obese man sitting in doctor's office


    Although the man was considered obese, his physical examination findings were fairly normal.

An obese 43-year-old male presents for evaluation of primary infertility and loss of libido. His wife is 37 and has regular periods but has moderate premature ovarian failure. Aside from the obesity, the physical examination was within normal limits.

Laboratory findings are as follows:

  • Testosterone 103 ng/dL (normal 300-900ng/dl)
  • Estradiol 54  (normal range less than 39ng/dl)
  • FSH  3.2 (normal range 2.0-11.0ng/dl)
  • LH 2.5 (normal 2.0-9.0ng/dl).

Semen analysis reveals 

  • volume of 3 mL (normal 2 – 5 mL)
  • concentration of 150 million/mL 
  • progressive motility: 72% (greater than 40% considered normal) 
  • strict sperm morphology: 8% normal forms (normal  greater than 4% normal forms). 


This case was provided by Stanton C. Honig MD, clinical professor of Urology at Yale School of Medicine, and Shu Pan, MD, resident in Urology at Yale Urology, in New Haven, Connecticut.ReferencesPavlovich CP, King P, Goldstein M, Schlegel PN. Evidence...

Submit your diagnosis to see full explanation.

This case was provided by Stanton C. Honig MD, clinical professor of Urology at Yale School of Medicine, and Shu Pan, MD, resident in Urology at Yale Urology, in New Haven, Connecticut.


Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001l 165: 837-41.

Helo S, Ellen J, Mechlin C, Feustel P, Grossman M, Ditkoff E, and McCullough A. A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal men. J Sex Med. 2015. 12(8):1761-9.

Chandrapal JC1, Nielson S2, Patel DP1, Zhang C3, Presson AP3, Brant WO1, Myers JB1, Hotaling JM1. Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels. BJU Int. 2016 Dec;118(6):994-1000.

Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. Testosterone supplementation versus clomiphene citrate for hypogonadism: an age matched comparison of satisfaction and efficacy. J Urol. 2014 Sep;192(3):875-9.

Correct answer: C

Loss of libido may be from many causes including the stress of trying to achieve a pregnancy. Hypogonadism may be responsible for loss of libido in this case. This patient most likely has hypogonadism from incomplete pituitary stimulation and also from peripheral aromatization of testosterone (T) to estradiol (E2). Increased E2 likely exerts feedback inhibition on the anterior pituitary, reducing testosterone level. Studies have shown that patients with severe male infertility have T:E2 ratio of 6.9 in comparison to men with normal spermatogenesis (T:E2 = 14.5), although the sperm parameters are within normal parameters in this case.

Clomiphene citrate binds to estrogen receptors in the hypothalamus and pituitary, blocking feedback inhibition, thereby increasing testosterone production. Anastrozole is an aromatase inhibitor and will reduce conversion of T to E2, raising the T:E2 ratio. While the patient’s semen parameters are above 50th percentile for the aforementioned categories, this would be the most reasonable initial treatment.  Although use of clomiphene citrate and anastrozole is an “off label” treatment, and should be documented as such, it may help the patient’s symptoms and will not have a negative effect on spermatogenesis.  Side effects of clomiphene citrate include mood swings, weight gain, hypertension and rarely increased risk of deep vein thrombosis.  All of these are uncommon. One should recheck testosterone, estradiol and FSH levels within 1-2 months of initiation of therapy.  There is minimal long term data on use of these drugs in men and therefore, monitoring in cases like this for long term use should include PSA and CBC as well.

Administering exogenous testosterone (A) will address the patient’s low libido but will also further suppress intratesticular testosterone and spermatogenesis. Testosterone is CONTRAINDICATED in men of reproductive years who are trying to achieve a pregnancy, as it will almost always lower sperm concentrations. Ephedrine (B) is a sympathetomimetic agent that may increase ejaculate volume in patients with low volume ejaculate affected by diabetes, partial sympathetic nerve injury from surgery such as anterior approach to back surgery or retroperitoneal lymph node dissection for testis cancer.  (The ejaculate volume is normal in this case). Daily LH replacement therapy is not appropriate for woman. In certain circumstances, the wife may be started on a hyperstimulation protocol to increase oocyte recruitment but this NOT a different and not daily regimen.  Recombinant-FSH (E) is used in rare cases of isolated FSH deficiency. This is not the case here.

Next hm-slideshow in Clinical Quiz