By Aly | First published October 25, 2020 | Last modified October 2, 2022
A claim has been originated by some in the online transgender community that the antiandrogen spironolactone increases visceral fat in transfeminine people and that this effect is irreversible. Visceral fat is a type of adipose tissue located in the intra-abdominal region which surrounds the internal organs (viscera) in that area. In excess, visceral fat causes the abdomen to look bloated and unattractive. The supposed phenomenon of visceral fat accumulation with spironolactone has sometimes been referred to by people in the transgender community as “spiro belly”. The claim is based on theory—specifically that spironolactone has been found to increase levels of the corticosteroid hormone cortisol due to its antimineralocorticoid activity and cortisol is known to increase visceral fat, which together imply that spironolactone might likewise be able to increase visceral fat. It is also based on claimed anecdotal observations of transfeminine people taking spironolactone, which are said to corroborate the hypothesis. Despite these claims owever, there is no actual direct scientific or medical literature to support the idea that spironolactone increases visceral fat, and there is considerable evidence contradicting it.
The influence of spironolactone on cortisol levels in clinical studies is variable and the magnitude of effect is limited. Hence, the clinical significance of increased cortisol levels with spironolactone is uncertain. Moreover, cortisol is an agonist of the glucocorticoid receptor (thereby producing glucocorticoid effects) and of the mineralocorticoid receptor (thereby producing mineralocorticoid effects). As already touched on, spironolactone has potent antimineralocorticoid activity (that is, mineralocorticoid receptor antagonism). Hence, even if spironolactone did increase cortisol levels enough to potentially increase visceral fat, its antimineralocorticoid activity could modify the capacity of cortisol to produce this effect. In relation to this, there is accumulating research to suggest that spironolactone may actually decrease visceral fat via its antimineralocorticoid activity. Antimineralocorticoids like spironolactone show antiadipogenic (anti-fat-accumulation) effects in vitro (Caprio et al., 2007; Caprio et al., 2011) and have been shown to decrease visceral fat in animals (Karakurt, 2008; Armani et al., 2014; Mammi et al., 2016; Olatunji et al., 2018). It is possible that they may also be able to do so in humans. Here are some notable literature excerpts relevant to this topic (Infante et al., 2019; Giordano, Frontini, & Cinti, 2016):
A possible explanation for [MR antagonists reducing cardiovascular morbidity and mortality more in patients with abdominal obesity] may be that patients with heart failure and abdominal obesity have higher aldosterone concentrations due to excessive secretion of specific aldosterone-releasing factors from [visceral adipose tissue]. […] Several studies on murine models of genetic and diet-induced obesity have widely reported beneficial effects of MR antagonism in terms of metabolic outcomes, such as body weight, fat mass, adipose tissue inflammation, insulin sensitivity, and lipid metabolism (Armani, Cinti, et al., 2014; Armani, Marzolla, et al., 2014; Garg & Adler, 2012; Guo et al., 2008; Hirata et al., 2009). Nevertheless, data on the outcomes of MR pharmacological blockade for prevention and treatment of obesity and metabolic syndrome are still scarce in humans (Tirosh et al., 2010). Of note, Tanko et al. demonstrated that the powerful MR antagonist drospirenone, in combination with estradiol, leads to a significant reduction of central fat mass and central fat mass/peripheral fat mass ratio in healthy post-menopausal women (Tankó & Christiansen, 2005). Moreover, another study has reported that MR antagonists significantly reduce body mass index and visceral fat area in patients with primary aldosteronism after a 1-year treatment period (Karashima et al., 2016). […] In light of these data, MR antagonism may be a useful therapeutic tool for prevention and treatment of cardiometabolic derangements observed in metabolic syndrome, even though additional studies are deemed necessary to confirm its impact on larger clinical settings.
An anti-obesity drug whose primary mode of action is to induce browning should act predominantly on visceral fat, thereby directly counteracting the major cause of obesity-associated metabolic disorders. Accumulation of abdominal visceral fat is, to some extent, linked to increased local levels and/or activity of androgen and glucocorticoid steroid hormones145,146. These hormones are also ligands of the mineralocorticoid receptors, which are found on white and brown adipocytes and could have a role in abdominal visceral fat accumulation and BAT to WAT conversion147–151.** […] **In this context, mineralocorticoid receptor antagonism has been shown to protect mice from the adverse obesogenic and metabolic effects of a high-fat diet via conversion of a substantial amount of visceral and subcutaneous WAT into BAT153. Given that mineralocorticoid receptor antagonists are widely prescribed diuretics, used to manage chronic heart failure, hyperaldosteronism and female hirsutism154, patients receiving such drugs should also be assessed for weight loss and metabolic parameters to establish whether these compounds have anti-obesity properties.
A number of studies have assessed the influence of antimineralocorticoids like spironolactone and eplerenone (another antimineralocorticoid) on visceral fat in humans. Spironolactone (12.5–100 mg/day) and eplerenone (25–100 mg/day) decreased visceral fat in people with pathologically high levels of aldosterone (a major endogenous mineralocorticoid hormone) (Karashima et al., 2016). A study of cisgender girls with polycystic ovary syndrome (PCOS) found that a combination of spironolactone (50 mg/day), pioglitazone, and metformin decreased visceral fat (Diaz et al., 2018). However, this study was of course confounded by the other medications. In addition to the preceding studies, many other clinical studies (at least 10) have assessed and similarly found no indication of increased visceral or abdominal fat with spironolactone (25–200 mg/day) (as measured by visceral fat directly or by indirect related measures like waist circumference or waist–hip ratio) (Wild et al., 1991; Lovejoy et al., 1996; Ganie et al., 2004; Meyer, McGrath, & Teede, 2007; Karakurt et al., 2008; Vieira et al., 2012; Ganie et al., 2013; Harmanci et al., 2013; Leelaphiwat et al., 2015; Alpañés et al., 2017). I was not able to identify any studies assessing visceral fat with higher doses of spironolactone (>200 mg/day). Additional studies are also underway to assess the possibility that spironolactone could decrease visceral fat.
With regard to the anecdotal claims of spironolactone increasing visceral fat in transfeminine people, it’s important to note that anecdotes are unreliable and are considered to be the lowest form of evidence in medicine. This is for well-founded reasons—succinctly, anecdotes very often don’t hold up when rigorous studies are conducted. It’s probable that excess abdominal fat—a problem which afflicts many—has been misattributed to spironolactone rather than to the real causes in transfeminine people. It’s notable in this regard that androgens are known to increase visceral fat and that men have twice as much visceral fat as women on average (Blouin, Boivin, & Tchernof, 2008; Zerradi et al., 2014). It’s possible that many transfeminine people may have excess visceral fat due to prior androgen exposure and that this visceral fat may not fully reverse with hormone therapy. As we know, hormone therapy unfortunately isn’t able to reverse all established bodily sexual dimorphism.
Besides increased visceral fat, many other serious adverse effects with spironolactone have been claimed. However, these claimed adverse effects are likewise based on anecdotes and theory, and there is a lack of direct clinical evidence to support such side effects. In actuality, spironolactone even at high doses appears to be well-tolerated per studies and systematic reviews. The claimed side effects of spironolactone may actually largely be due to phenomena like nocebo and misattribution—which can be controlled for in systematic studies but not in the case of anecdotal observations.
To summarize, no research, animal or clinical, has found increased visceral fat with spironolactone, and there is accumulating evidence that spironolactone may cause the very opposite effect. More studies are needed to further characterize this possible benefit of spironolactone in humans however.
- Alpañés, M., Álvarez-Blasco, F., Fernández-Durán, E., Luque-Ramírez, M., & Escobar-Morreale, H. F. (2017). Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial. European Journal of Endocrinology, 177(5), 399–408. [DOI:10.1530/eje-17-0516]
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- Karashima, S., Yoneda, T., Kometani, M., Ohe, M., Mori, S., Sawamura, T., Furukawa, K., Seta, T., Yamagishi, M., & Takeda, Y. (2015). Comparison of eplerenone and spironolactone for the treatment of primary aldosteronism. Hypertension Research, 39(3), 133–137. [DOI:10.1038/hr.2015.129]
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