Michael S. Irwig

Persistent Sexual Side Effects of Finasteride: Could They Be Permanent?

INTRODUCTION Finasteride has been associated with sexual side effects that may persist despite discontinuation of the medication. In a clinical series, 20% of subjects with male pattern hair loss reported persistent sexual dysfunction for ≥6 years, suggesting the possibility that the dysfunction may be permanent. These subjects also reported a wide range of symptoms including changes in cognition, ejaculate quality, and genital sensation. Other medications have been associated with irreversible neurological effects, such as phenothiazines with tardive dyskinesias. AIM To prospectively study whether the persistent sexual side effects associated with finasteride resolve or endure over time. METHODS Subjects (N = 54) with persistent sexual side effects associated with finasteride were reassessed after 9-16 months (mean 14 months). All subjects were otherwise healthy young men without any baseline sexual dysfunction, medical conditions, psychiatric conditions, or use of oral prescription medications prior to taking finasteride for male pattern hair loss. MAIN OUTCOME MEASURE Scores from the Arizona Sexual Experience Scale (ASEX). RESULTS The participation rate was 81%. At reassessment persistent sexual side effects continued to be present in 96% of subjects. According to the ASEX scores, 89% of subjects met the definition of sexual dysfunction. Neither the length of finasteride use nor the duration of the sexual side effects correlated to changes in scores of sexual dysfunction. CONCLUSION In most men who developed persistent sexual side effects (≥3 months) despite the discontinuation of finasteride, the sexual dysfunction continued for many months or years. Although several rat studies have shown detrimental changes to erectile function caused by 5 alpha reductase inhibitors, the persistent nature of these changes is an area of active research. Prescribers of finasteride and men contemplating its use should be made aware of the potential adverse medication effects.

Decreased Alcohol Consumption Among Former Male Users of Finasteride with Persistent Sexual Side Effects: A Preliminary Report

BACKGROUND There is a robust literature in rodents, but not in humans, on the interaction between finasteride and alcohol, particularly as it relates to neurosteroids. Finasteride has been shown to reduce alcohol intake and suppress alcohol preference in male mice. This study examines the role of finasteride in alcohol consumption in humans with male pattern hair loss. METHODS The subjects were 83 otherwise healthy men who developed persistent sexual side effects associated with finasteride, despite the cessation of this medication for at least 3 months. Information from standardized interviews was collected regarding medical histories, sexual function, and alcohol consumption before and after finasteride use. RESULTS Of the 63 men who consumed at least 1 alcoholic beverage/wk prior to starting finasteride, 41 (65%) noted a decrease in their alcohol consumption after stopping finasteride. This reduction typically began before discontinuing finasteride. Twenty men (32%) reported no change in their alcohol consumption, and 2 men (3%) reported an increase in their alcohol consumption. For the 63 consumers of alcohol, the mean number (± SE) of alcoholic beverages/wk declined from 5.2 ± 0.7 before finasteride to 2.0 ± 0.3 after finasteride (p < 0.0001). A major study limitation is the lack of a comparison group. CONCLUSIONS In former male users of finasteride who developed persistent sexual side effects, 65% noticed a decline in their alcohol consumption as compared to baseline. This finding is consistent with finasterides ability to modulate alcohol intake in rodents. Further research is needed on the central nervous system effects of finasteride in humans.

Testosterone therapy for transgender men

Testosterone therapy is a cornerstone of medical treatment for transgender men who choose to undergo it. The goal of testosterone therapy is usually to achieve serum testosterone concentrations in the male reference range. Testosterone has several desired effects as well as undesired and unknown effects. The desired effects include increased facial and body hair, increased lean mass and strength, decreased fat mass, deepening of the voice, increased sexual desire, cessation of menstruation, clitoral enlargement, and reductions in gender dysphoria, perceived stress, anxiety, and depression. Achievement of these goals comes with potential undesired effects and risks including acne, alopecia, reduced HDL cholesterol, increased triglycerides, and a possible increase in systolic blood pressure. An additional benefit of testosterone therapy (with or without mastectomy) is a reduced risk of breast cancer. Most of the effects of testosterone start to develop within several months of starting therapy, although facial hair and alopecia continue to develop after 1 year. A major limitation in the study of testosterone therapy for transgender men is a paucity of high-quality data due to a shortage of randomised controlled trials (partly because of ethical issues), few prospective and long-term studies, the use of suboptimum control groups, loss to follow-up, and difficulties in recruitment of representative samples of transgender populations.

High Rates of Depression and Depressive Symptoms among Men Referred for Borderline Testosterone Levels

INTRODUCTION Men referred for borderline testosterone levels represent an increasingly common clinical scenario, yet there is little literature on this population. AIM We hypothesized that men referred for borderline testosterone levels would have higher rates of depression and depressive symptoms than the general population. METHODS Subjects included 200 adult men (mean age of 48 years old) referred for borderline total testosterone levels between 200 and 350 ng/dL (6.9-12 nmol/L). Collected data included demographic information, medical histories, medication use, signs and symptoms of hypogonadism, and assessments of depressive symptoms and/or a known diagnosis of depression or use of an antidepressant. MAIN OUTCOME MEASURES The main outcome measure was a combination of known depression, current use of an antidepressant, and/or depressive symptoms according to the Patient Health Questionnaire 9 (PHQ-9) with scores ≥10 considered positive. RESULTS Depression and/or depressive symptoms were present in 56% of the subjects. This rate was significantly higher than rates of 6-23% (PHQ-9 scores ≥10) seen in general populations. Antidepressant use was 25%. The population was notable for high rates of overweight/obesity and physical inactivity. Common symptoms were erectile dysfunction, decreased libido, fewer AM erections, low energy, and sleep disturbances. CONCLUSIONS While sexual and nonspecific symptoms (i.e., fatigue) likely prompted measurements of testosterone in this selected population, clinicians should recognize the high rates of depression and depressive symptoms in men referred for borderline testosterone levels. Clinicians should consider screening for depression/depressive symptoms and overweight and unhealthy lifestyle risk factors in men referred for tertiary care for potential hypogonadism.

Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia.

Purpose of reviewTo examine the clinical and basic studies regarding persistent adverse effects associated with 5&agr; reductase inhibitor treatment for androgenetic alopecia. Recent findingsRecent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5&agr;-androstane-3&agr;,17&bgr;-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation. Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase. Finally, 5&agr; reductase inhibitors have also been found to alter semen parameters in healthy men. SummaryMultiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5&agr; reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.

Persistent Sexual and Nonsexual Adverse Effects of Finasteride in Younger Men

INTRODUCTION Recent studies have reported persistent sexual and nonsexual adverse effects associated with the 5α-reductase inhibitor finasteride. AIMS The first aim was to review the clinical studies of persistent sexual and nonsexual adverse effects associated with finasteride in younger men who took the medication for treatment of male pattern hair loss. The second aim was to place these findings into context with what is known from basic and clinical studies about the hormones and neurosteroids affected by finasteride. METHODS Relevant published literature on the topic was reviewed. Clinical symptomatology in humans was correlated with findings from rodent models to investigate possible underlying mechanisms. MAIN OUTCOME MEASURES Persistent sexual and nonsexual adverse effects were summarized. RESULTS Two clinical studies have described persistent side effects associated with finasteride use in otherwise healthy younger men. The sexual side effects are typically present in multiple domains that include erectile dysfunction, low libido, and decreased orgasms. Erectile dysfunction may be related to low levels of dihydrotestosterone, which has been shown to be an important androgen in both human and animal studies. Nonsexual side effects include depression and decreased alcohol consumption that are linked to the neurosteroid allopregnanolone in both human and animal studies. Three men with persistent side effects associated with finasteride were found to have lower plasma and cerebrospinal fluid levels of several neurosteroids. CONCLUSIONS Persistent adverse effects of finasteride in younger men include erectile dysfunction, low libido, lack of orgasms, depression, and decreased alcohol consumption. One study has found lower levels of several neurosteroids in this population. Out of the various persistent side effects, erectile dysfunction and decreased alcohol consumption have been the most studied in animal models. Further research is needed on who is susceptible to the persistent adverse side effects of finasteride and on the underlying mechanisms of the medication. Irwig MS. Persistent sexual and non-sexual adverse effects of finasteride in younger men. Sex Med Rev 2014;2:24-35.

Male hypogonadism and skeletal health.

Purpose of reviewTo examine the role of testosterone in skeletal health in men. Recent findingsEvidence from recent studies shows that the contributing role of testosterone to osteoporosis is modest and likely trumped by other factors such as estradiol levels. A few studies have documented an association between low testosterone levels and lower bone mineral density (BMD), increased prevalence of osteoporosis of the hip and low bone mass-related fractures. Other studies, however, have found that testosterone levels are not independent predictors of bone resorption or formation markers, BMD at the hip or incident fractures. Curiously, hypogonadism does not account for the increased osteoporosis seen in men with Klinefelter Syndrome. Regardless of hypogonadism status, two recent clinical trials have found fewer new morphometric vertebral fractures in men treated with zoledronic acid and increased BMD in men treated with denosumab. Denosumab was also shown to modestly increase bone-metastasis-free survival in men with castration-resistant prostate cancer. SummaryAlthough male hypogonadism is associated with osteoporosis, estradiol is likely to be the more important hormone for bone health. Although a few large randomized controlled trials have been conducted in men with low bone density (a subset of whom have hypogonadism), more trials are needed, particularly with fractures as the main outcome.

Autoimmune thyroid disease and Sjögren syndrome.

The thyroid, salivary, and lacrimal glands are susceptible to immunologic damage, which can be expressed as an organspecific autoimmune disease such as thyroiditis, or a systemic autoimmune disease such as primary Sjögren syndrome (pSS). Sjögren syndrome is characterized by the progressive destruction of the exocrine parotid and lacrimal glands, causing mucosal and conjunctival dryness (sicca syndrome). The serology of patients with pSS often shows elevated levels of antibodies including antinuclear antibody, rheumatoid factor, Ro (SS-A), and La (SS-B). There is a growing body of literature suggesting an increased risk of autoimmune thyroid disease (AITD) in individuals with pSS and an increased risk of pSS in individuals with AITD. We describe the case of a 41-year-old man who presented with severe hypothyroidism and was also found to have pSS by serology and lip biopsy.

Bone health in hypogonadal men.

Purpose of review To examine bone health in relation to testosterone and male hypogonadism. Recent findings An emerging area of research pertains to the newly described bone-testis axis. In particular, the peptide hormone osteocalcin, which is made by bone and fat, appears to play a role in testosterone production. Inconsistent weak associations have been noted between vitamin D deficiency or insufficiency and lower testosterone levels. Although a high prevalence of hypogonadism is associated with opioid use, HIV and transfusion-dependent thalassemia, the risk of fracture in these populations is unclear. In fact, one study found that the modest increase in fractures among opioid users was attributed to central nervous system adverse effects of the medications as opposed to chronic hypogonadism. In terms of therapy, many small studies have found that testosterone replacement therapy increases bone mineral density in hypogonadal men, including men with hypopituitarism. Summary Further research is needed on the cross-talk that occurs in the bone-testis axis. When it comes to managing men with hypogonadism, the benefit of testosterone replacement therapy on prevention of incident fractures is uncertain. Large, long-term randomized controlled trials are needed with fracture as the primary outcome.

Self-Castration by a Transsexual Woman: Financial and Psychological Costs: A Case Report

INTRODUCTION The out-of-pocket cost for an elective orchiectomy, which is often not covered by health insurance, is a significant barrier to male-to-female transsexuals ready to proceed with their physical transition. This and other barriers (lack of access to a surgeon willing to perform the operation, waiting times, and underlying psychological and psychiatric conditions) lead a subset of transsexual women to attempt self-castration. Little information has been published on the financial costs and implications of self-castration to both patients and health care systems. AIM We compare the financial and psychological costs of elective surgical orchiectomy vs. self-castration in the case of a transsexual woman in her 40s. METHODS We interviewed the patient and her providers and obtained financial information from local reimbursement and billing specialists. RESULTS After experiencing minor hemorrhage following the self-castration, our patient presented to the emergency department and underwent a bilateral inguinal exploration, ligation and removal of bilateral spermatic cords, and complicated scrotal exploration, debridement, and closure. She was admitted to the psychiatric service for a hospital stay of three days. The total bill was U.S.