Testosterone deficiency is diagnosed by a serum total testosterone level below 300 ng/dL in combination with symptoms such as decreased energy and libido. These symptoms can be ameliorated by restoring serum testosterone to the physiologic range with testosterone therapy (TT). There are numerous forms of testosterone therapy, such as injectable, transdermal, nasal, and subcutaneous applications. There are also multiple formulations of injection, such as testosterone cypionate, testosterone enanthate, and testosterone undecanoate. Testosterone undecanoate (TU) is a long-acting ester formulation of testosterone that can be provided in an injectable or oral form. Oral testosterone undecanoate is marketed as Andriol, Jatenzo, Tlando, and Kyzatrex. Oral TU provides a convenient option for many patients, which may increase compliance with TT. Injectable testosterone undecanoate is marketed as Aveed and Nebido. Injectable TT remains the most cost-effective therapeutic option and is appropriate for most patients as an initial therapy. This review describes the pharmacokinetics of these testosterone undecanoate products and provides a guide for prescribers using these medications. While many forms of testosterone are appropriate for TT, a patient-centered discussion focused on goals of care should best guide physician prescription of these medications.

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Introduction Allopregnanolone is a GABAnergic neurosteroid. Reduced concentration of allopregnanolone in the cerebrospinal fluid (CSF) and serum are closely associated with several neuropsychiatric conditions, including Alzheimer’s disease, anxiety disorders, premenstrual dysphoric disorder, and postpartum depression. Allopregnanolone is a progesterone metabolite predominantly synthesized in women in the ovaries and prior literature shows the menstrual cycle directly affects serum and CSF allopregnanolone concentrations. We hypothesize that allopregnanolone’s biosynthesis is similarly affected by exogenous hormonal contraceptives. In the United States, 65% of reproductive-aged women use hormonal contraceptives and their discontinuation is commonly attributed to adverse changes in mood; yet, little is understood when it comes to what and how specific components of hormonal contraceptives affect mood and how to manage such effects. Objective We aim to review current literature and propose a study to understand the connection between allopregnanolone and the adverse mood effects of hormonal contraceptives in order to improve women’s health. Methods We conducted a semi-systematic literature search, using PubMed Central and other databases, compiling peer-reviewed material using keywords including allopregnanolone AND hormonal contraceptives; combined oral contraceptive; progestin; suppression; levonorgestrel, ethinyl estradiol, medroxyprogesterone. All languages of publication were included where reliable translations were available. Studies were excluded if they did not include serum and/or CSF measurements of allopregnanolone. Results Rodent studies demonstrated that exogenous hormonal contraceptives reduce both the serum and CSF concentration of allopregnanolone. Human studies analyzing only serum allopregnanolone concentrations showed the same results, but no human studies analyzing CSF allopregnanolone concentrations were identified. Only two human studies have examined serum allopregnanolone levels and mood, and no studies have done so in the context of exogenous hormonal contraceptive use. Conclusions While exogenous sex hormones, namely progestins, affect allopregnanolone levels in rodents, their impact on both allopregnanolone levels and mood remains inconclusive and under-researched in humans. We propose a large multi-arm study on humans analyzing CSF and serum allopregnanolone and mood effects following administration of hormonal contraceptives to assess how contraceptives affect allopregnanolone metabolism in connection to adverse mood effects. This research will allow clinicians to better tailor contraceptive selection. Disclosure No

Disorders of sperm production can be classified quantitatively as oligospermia (low sperm count) or azoospermia (no sperm during ejaculation). Numerous genes have been implicated in spermatogenesis. We describe a case of two identical twins who presented with different reproductive capabilities. One brother was infertile due to azoospermia, and the other, although oligospermic, previously naturally fathered a child. They were found to have differential gene expression based on RNA sequencing analysis. In the man with azoospermia, we found elevated E2F1 and HOXB9 gene expressions when compared with his brother, suggesting that the increased RNA expression of these genes could influence sperm production.