低睾固酮 (testosterone)與依非韋倫 (efavirenz)、體脂增加和年齡增長有關

資料來源：Felicia Bamgbose / 2022 年 11 月 24 日 / aidsmap / 則團法人台灣紅絲帶基金會編譯

圖片來源：VGstockstudio/Shutterstock.com

法國一項針對愛滋病毒控制良好的男性的研究確定了低睾丸激素的風險因素。 研究發現，年齡超過 43 歲、使用依非韋倫作為治療、身體脂肪百分比較高或最低 CD4 計數低於 200 都與較低水平的睾丸激素有關。利用這些風險因素，有可能改進低睾固酮的早期診斷並提供替代治療，以避免骨骼、心理健康和性方面的問題。

在使用廣泛有效的抗反轉錄病毒治療之前，低睾固酮——也稱為性腺機能減退——是愛滋病毒感染者最常見的內分泌問題。 睾丸激素是睾丸產生的一種性激素，對男性特徵的發育很重要，可促進骨骼生長、肌肉生長和精子生成。 低睾固酮會導致骨密度降低、性功能障礙、肌肉質量下降和抑鬱，因此會對一個人的生活品質產生巨大影響。

在之前的研究中，低睾固酮水平與晚期 HIV 感染者密切相關。 據估計，低睾固酮的盛行率在 HIV 感染者中佔 9% 至 70%。 瑪麗·拉沙特爾 (Marie Lachâtre) 博士及其同事對從未患過愛滋病定義疾病的男性進行了低睾固酮水平的首次發表研究，以了解儘管進行了病毒抑制和抗反轉錄病毒治療，是否仍然存在問題。

發表在 AIDS 上的研究於 2013 年 1 月至 2016 年 6 月在法國進行。 總共招募了 231 名 HIV 感染者，他們大多在三、四十歲左右，並且正在接受病毒載量抑制的 HIV 治療。 收集了兩次清晨的血樣，間隔八天，以測量平均游離睾固酮水平（不與血液中的任何其他蛋白質結合）和總體睾固酮水平。 清晨的樣本是最好的，因為一天中的水平會發生變化。 以前有伺機性感染、肝臟或腎臟問題的男性以及接受睾固酮、性激素或合成代謝類固醇治療的男性都被排除在外。

游離睾固酮水平低於 70 顯示睾丸功能低下（性腺功能減退症）。 在 HIV 感染者中，游離睾固酮水平的測量優於總睾固酮水平，因為另一種激素（性激素結合球蛋白）的增加會降低總睾固酮的準確性。測量其他性激素以確認低睾固酮的原因；低睾固酮可能是睾丸無法產生睾固酮（原發性性腺功能減退症）或大腦未向睾丸發送信號以產生睾固酮（繼發性性腺功能減退症）。記錄了參與者的人口統計數據，以及其他因素，例如勃起功能、生活質量、抑鬱、骨骼健康和體重。

總體而言，20 名男性 (8.7%) 的睾固酮水平較低，是同齡普通人群的兩倍。所有 20 人都患有繼發性性腺功能減退症，其中來自大腦的信號問題是睾丸激素水平低的原因。確定的低睾固酮的風險因素包括超過 43 歲的中位數，CD4 計數最低低於 200，使用包括依非韋倫在內的治療方案以及總脂肪百分比大於 19%。總脂肪百分比將體內脂肪含量與總體重量進行比較，男性的預期值約為 15%，但女性的預期值要高得多。增加的脂肪組織促使睾固酮轉化為雌激素。研究人員假設依非韋倫還可能增加睾固酮轉化為雌激素，從而降低睾固酮水平並導致乳腺組織生長。他們還提出，感染 HIV 的男性中低睾固酮水平的增加是由於 HIV 的早衰效應。

在測量勃起功能障礙和生活質量惡化時，55% 的參與者報告了這些問題。三分之一的參與者有抑鬱症狀，18% 的參與者診斷為骨質疏鬆症。然而，重要的是要注意，在這項研究中，這些症狀中的任何一種與低睾固酮水平之間沒有顯著聯繫，這可能是由於研究規模較小。

篩查可以針對低睾固酮的高危人群，例如那些使用依非韋倫 (efaverinz)、總脂肪至少為 19% 或年齡超過 43 歲的人。在這些人群中清晨採集游離睾固酮樣本可以更早發現低睾固酮水平。 反過來，這可能會導致更快地獲得替代睾固酮治療並改善生活質量。

參考文獻：

Lachâtre M et al. 性腺功能減退症：在接受有效的抗反轉錄病毒聯合治療的中青年 HIV 陽性男性中被忽視的合併症。《愛滋病》 36：1061-1071，2022（開放獲取）。

doi: 10.1097/QAD.0000000000003176

Low testosterone is linked to efavirenz, increased body fat and older age

Felicia Bamgbose / 24 November 2022 / aidsmap

VGstockstudio/Shutterstock.com

A French study of men living with well-controlled HIV identified risk factors for low testosterone. It found that being aged over 43, use of efavirenz as treatment, having a higher percentage of body fat or a nadir CD4 count of less than 200 were all linked to lower levels of testosterone. Using these risk factors, it may be possible to improve early diagnosis of low testosterone and provide replacement treatment, to avoid problems with bones, mental health and sex.

Prior to the use of widespread effective antiretroviral treatment, low testosterone – otherwise known as hypogonadism – was the most common endocrine problem in people living with HIV. Testosterone is a sex hormone produced by the testicles, which is important for development of male characteristics and encourages bone growth, muscle growth and sperm production. Low testosterone can cause a decrease in bone density, sexual dysfunction, decreased muscle mass and depression, so can have a huge impact on a person’s quality of life.

In previous studies, low testosterone levels were strongly associated with people who had advanced HIV. Estimates of the prevalence of low testosterone have ranged from 9% to 70% of people living with HIV. Dr Marie Lachâtre and her colleagues have conducted the first published research on low testosterone levels in men who have never had an AIDS-defining illness, to see if there was still a problem, despite viral suppression and antiretroviral treatment.

The research published in AIDS was conducted from January 2013 until June 2016 in France. In total, 231 men living with HIV who were mostly in their late thirties or forties and were on HIV treatment with a suppressed viral load were recruited. Two early morning blood samples were collected, eight days apart, to measure average free testosterone levels (not bound to any other protein in the blood) and overall testosterone levels. Early morning samples are best, as levels change throughout the day. Men with previous opportunistic infections, liver or kidney problems and those on treatment involving testosterone, sex hormones or anabolic steroids were all excluded.

Free testosterone levels of less than 70 indicate low functioning testicles (hypogonadism). In people living with HIV, measurement of free testosterone levels is preferable to total testosterone levels due to the increase of another hormone (sex hormone binging globulin), which makes total testosterone less accurate. Other sex hormones were measured to confirm the reason for low testosterone. Low testosterone can be either a failure of the testicles to make testosterone (primary hypogonadism) or the brain not sending signals to the testicles to make testosterone (secondary hypogonadism). Participant demographics were recorded, as were other factors, such as erectile function, quality of life, depression, bone health and weight.

Overall, 20 (8.7%) of the men were found to have low testosterone, which is twice the rate in the general population of the same age. All 20 had secondary hypogonadism, in which a problem with the signalling from the brain is the cause of low testosterone. Risk factors identified for low testosterone included being over the median of 43 years old, having a lowest ever CD4 count of less than 200, using a treatment regimen including efavirenz and having a total fat percentage greater than 19%. The total fat percentage compares the level of fat in the body to overall weight, with the expected value for men being around 15%, but much higher for women. Increased fatty tissue encourages testosterone to be converted to oestrogen. The researchers hypothesised that efavirenz may also increase testosterone conversion into oestrogen, which lowers testosterone levels and causes the growth of breast tissue. They also suggested that the increase in low testosterone amongst men living with HIV was due to the early ageing effect of HIV.

When measuring both erectile dysfunction and worsening of quality of life, 55% participants reported these issues. One third of participants had symptoms of depression and 18% a diagnosis of osteoporosis. However, it is important to note that there was no significant link between any of these symptoms and low testosterone levels in this study, possibly due to the small size of the study.

Screening could be targeted at the higher risk groups for low testosterone such as those who use efaverinz, have a total body fat of at least 19% or who are aged over 43. Taking an early morning free testosterone sample in these groups could enable earlier detection of low testosterone levels. In turn this could lead to faster access to treatment with replacement testosterone and an improved quality of life.  

References

Lachâtre M et al. Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy. AIDS 36: 1061-1071, 2022 (open access).

doi: 10.1097/QAD.0000000000003176