This article is a rough draft!
This means that although usable, the article may be missing citations, contain grammar errors, and likely still needs to be expanded upon.
|Dosage range:||Oral: 25–400 mg/day|
|Brand names:||Aldactone, Berlactone, Spiractin|
|Elimination half-life||1.4 hours|
Spironolactone is an antiandrogen medication that is used to treat a variety of conditions, such as hypertension, fluid retention, cirrhosis of the liver and nephritic syndrome. It is also used to treat or prevent low potassium levels in the blood.
It is by far the most common antiandrogen prescribed to transgender women for the use of blocking the production of testosterone to assist them in their transition. However, despite its ubiquity, it has a number of negative side effects when used over a long period of time.
Method of Action
Spironolactone is a moderately strong antiandrogen. It acts as an antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). By blocking the androgen receptor, spironolactone inhibits the effects of androgens in the body. This antiandrogenic activity of spironolactone is mainly responsible for its therapeutic efficacy in the treatment of androgen-dependent skin and hair conditions such as acne, male pattern hair loss, and as a component of feminizing hormone therapy for transgender women. 
It is also primarily responsible for some of its effects, like breast tenderness, gynecomastia, feminization, and demasculinization in men. Blockade of androgen signaling in the breast allows the actions of estrogens in this tissue. Although useful as an antiandrogen in women, who have low testosterone levels compared to men, spironolactone is described as having relatively weak antiandrogenic activity for them.
Spironolactone is what is referred to as a weak steroidogenesis inhibitor. That is, it inhibits enzymes involved in the production of steroid hormones such as testosterone. Over time, however, increasingly high dosages of spironolactone may be needed as the body may increase testosterone production to compensate for the effects of this androgen receptor antagonism.
Spironolactone may not consistently decrease the production of testosterone at any clinically significant levels. This results in testosterone's compensatory up-regulation, sometimes exceeding the amount that is being blocked from the androgen receptors, thus resulting in a progressively increased tolerance to the substance over long periods of time.
Spironolactone also acts as a weak inhibitor of the enzyme that is involved in the conversion of estradiol into estrone. It has been found in some studies to increase levels of estradiol, although many other studies have found no changes in estradiol levels. The mechanism of how spironolactone increases estradiol levels is unclear, but it may involve the undoing of the body's systematic breakdown of estradiol into estrone. Increased levels of estradiol with spironolactone may be involved in its side effects such as breast tenderness, breast enlargement, and gynecomastia in women and men.
Spironolactone is a potent antimineralocorticoid. That is, it is an antagonist of the mineralocorticoid receptor (MR), the biological target of mineralocorticoids like aldosterone and 11-deoxycorticosterone. By blocking the MR, spironolactone inhibits the effects of mineralocorticoids in the body. The antimineralocorticoid activity of spironolactone is responsible for its therapeutic efficacy in the treatment of edema, high blood pressure, heart failure, hyperaldosteronism, and ascites due to cirrhosis. It is also responsible for many of the side effects of spironolactone, such as urinary frequency, dehydration, hyponatremia, low blood pressure, fatigue, dizziness, metabolic acidosis, decreased kidney function, and its risk of hyperkalemia. Due to the antimineralocorticoid activity of spironolactone, levels of aldosterone are significantly increased by the medication, probably reflecting an attempt of the body to maintain homeostasis.
The use of spironolactone may result in the following side effects...
- Increased urination
- Brain fog
- Low blood pressure
- Decreased kidney function
- Increases cortisol
The usual starting dose is 50-100 mg daily in one or two doses up to a maximum of 400 mg daily. Hormone levels should be monitored through blood tests to ensure you are receiving the appropriate dosages.
Spironolactone is marketed under a large number of brand names throughout the world. The major brand name of spironolactone is Aldactone. Other important brand names include Aldactone-A, Berlactone, CaroSpir, Espironolactona, Espironolactona Genfar, Novo-Spiroton, Prilactone (veterinary), Spiractin, Spiridon, Spirix, Spiroctan, Spiroderm (discontinued), Spirogamma, Spirohexal, Spirolon, Spirolone, Spiron, Spironolactone Actavis, Spironolactone Orion, Spironolactone Teva, Spirotone, Tempora (veterinary), Uractone, Uractonum, Verospiron, and Vivitar.
|Aldactone 100mg x 20||27.00$||21.60$||AllRealMedications||Ships from Turkey|
|Aldactone 100mg x 30||16.80£||Aphrodite's||Ships from Portugal|
|Aldactone 100mg x 30||14.04$||11.60$||AllDayChemist||Various worldwide centers|
|Aldactone 100mg x 96||60.00€||52.50€||ShapeShifter||Ships from Turkey|
|Aldactone 25mg x 15||3.16$||2.85$||UnitedPharmacies||(US-Centric)|
|Aldactone 50mg x 90||29.50$||21.63$||InHousePharmacy||Ships from Vanuatu (Oceania)|
|Hyles 100mg x 10||15.90€||12.72€||ThailandPharmacy||Ships from Thailand|
|Hyles 100mg x 10||4.45$||4.05$||FabSkinHouse||Ships from Thailand|
|Hyles 100mg x 100||49.99$||Request||Amazon4Health||Ships from Thailand|
|Hyles 25mg x 10||6.00€||4.80€||ThailandPharmacy||Ships from Thailand|
Spironolactone can be purchased in tablet form through a variety of sources such as online pharmacies. However, it can also be purchased in bulk powdered form through vendors on websites such as Alibaba. From personal experience, Alibaba is substantially cheaper and some vendors will often go to great lengths to get your product to you by deliberately mislabelling packages in order to more easily get them through customs. We have personally had good luck with this particular vendor. It is also worth noting that in order to purchase products from these sites, you will need to personally contact the vendor and negotiate a price with them.
- Spironolactone and Endocrine Dysfunction D. LYNN LORIAUX, RAYMOND MENARD, ADDISON TAYLOR, JULIO C. PITA, and RICHARD SANTEN Annals of Internal Medicine 1976 85:5, 630-636 https://www.acpjournals.org/action/showCitFormats?doi=10.7326%2F0003-4819-85-5-630
- The World Professional Association for Transgender Health (WPATH) (2011). "Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People" (PDF). Archived from the original (PDF) on 23 May 2012. Retrieved 27 May 2012.
- Wylie C. Hembree, Peggy Cohen-Kettenis, Henriette A. Delemarre-van de Waal, Louis J. Gooren, Walter J. Meyer, III, Norman P. Spack, Vin Tangpricha, Victor M. Montori, Endocrine Treatment of Transsexual Persons:An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 94, Issue 9, 1 September 2009, Pages 3132–3154, https://doi.org/10.1210/jc.2009-0345
- Prior, J.C., Vigna, Y.M. & Watson, D. Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Arch Sex Behav 18, 49–57 (1989). https://doi.org/10.1007/BF01579291
- Donald Poirier, “ Inhibitors of 17β-Hydroxysteroid Dehydrogenases”, Current Medicinal Chemistry (2003) 10: 453. https://doi.org/10.2174/0929867033368222
- Donald Poirier, “ Advances in Development of Inhibitors of 17β-Hydroxysteroid Dehydrogenases”, Anti-Cancer Agents in Medicinal Chemistry (2009) 9: 642. https://doi.org/10.2174/187152009788680000
- 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development | https://doi.org/10.1530/JOE-16-0600
- Diamanti-Kandarakis, E., Tolis, G. & Duleba, A.J. Androgens and Therapeutic Aspects of Antiandrogens in Women. Reprod. Sci. 2, 577–592 (1995). https://doi.org/10.1177/107155769500200401