Spironolactone for acne in PCOS #123
Is it worth it?
Hello everyone,
Today, I would like to answer a question from a dear reader about a medication she was offered for treating acne: spironolactone. This medication is also used to treat high blood pressure. We have a similar situation here to Metformin. A drug approved for a different purpose is also being offered to us.
You might wonder why is that.
PCOS is a syndrome, not a disease.
A syndrome is a group of symptoms that happen together but don’t have a reason why or how they are interlinked. Because of this, you can pick these symptoms apart and find a medication that alleviates those symptoms. For our insulin resistance, we take Metformin (a drug for diabetes); for our irregular periods, we take the pill, and it seems that for acne, it can be Spironolactone.
What is Spironolactone?
Spironolactone, sold under the brand name Aldactone® among others, is a medication that functions primarily as an aldosterone antagonist. Aldosterone is a steroid hormone produced by the adrenal glands that plays a crucial role in regulating blood pressure by controlling sodium and potassium levels in the body.
The primary aim of this medication is used for heart failure, hypertension (when other treatments are insufficient), fluid retention and hyperaldosteronism (excessive aldosterone production).
Hmm..so how did it end up being used for Acne?
Spironolactone also shows powerful anti-androgenic effects. This is how it works:
It competes with DHT for androgen receptors in the skin - the main reason for hormonal acne is the effect androgens have on the sebum production of our skin cells - you can read more about this in our acne article:
Increases the level of sex hormone binding globulins (SHBG) in the circulation, which helps lower testosterone - you can also read more about this PCOS protein as I like to call it below:
It is so popular that the prescribing rates of spironolactone for acne in women rose by nearly 300% from 2017 to 2020.
Now you can imagine that some big questions arise:
If this drug is meant for something else, is it safe to take it if you don’t have heart failure or blood pressure problems?
How much research is there to prove its safety?
Let’s answer them.
The use of Spironolactone for acne
Spironolactone was originally discovered in 1957 and introduced in the market in 1959. It has been around for a while. In 1962, gynecomastia (breast enlargement in males) was first reported as a side effect of spironolactone use. This side effect was later understood to be related to spironolactone's antiandrogenic properties, as gynecomastia was identified in 1967 as a major side effect of androgen receptor antagonists. There were also quite a few mice studies where this anti-androgenic effect was observed.
Essentially, man boobs are what made it possible. Later, in 1978, Spironolactone was first studied in treating hirsutism (excess hair due to high androgens). Transgender women also use it.
Does Spironolactone work?
The SAFA (Spironolactone for Adult Female Acne) study, completed in 2023, was a large-scale clinical trial involving over 400 women with acne. It demonstrated that spironolactone significantly improved acne symptoms and quality of life compared to placebo after 12 and 24 weeks of treatment.
The FASCE (Female Acne Spironolactone vs doxyCycline Efficacy) study, published in 2024, compared spironolactone to doxycycline in 133 women with moderate acne. It found that spironolactone was significantly more effective than doxycycline after 6 months of treatment, with improved acne scores, lesion counts, and quality of life.
Is it safe?
In terms of safety, an 8-year follow-up study assessed the long-term safety and tolerance of spironolactone in 91 women with acne.
The women were followed for up to 8 years, and the mean treatment length with spironolactone was 28.5 months, ranging from 0.5 to 122 months. The total exposure to spironolactone in the surveyed group was 200 person-years, and the cumulative follow-up time was 506 person-years.
The key findings of the study are:
Safety: No cases of severe illness were reported during the 8-year follow-up period that were thought to be attributable to spironolactone use.
Side Effects: Side effects were common, occurring in 59% of patients, but these only resulted in the cessation of the drug in 15% of cases.
Common Side Effects: The most frequently reported adverse effects were diuretic effect (29%) and menstrual irregularities (22%), including spotting (12%), increased flow (6%), and decreased flow (4%).
Other reported side effects included breast tenderness (17%), breast enlargement (4%), fatigue (15%), headache (13%), dizziness (12%), and lightheadedness (11%).
Ok, so menstrual irregularities can be a problem, but what if you already have PCOS and irregular periods? Does it make it worse?
When it comes to research explicitly done on women with PCOS, the research is little and of lower quality.
The spotting side effect might be due to Spironolactone’s impact on reducing estrogen levels (specifically estradiol) and thinning the lining of the uterus (endometrium). This seems to particularly affect those who already had lower estrogen levels before starting treatment. The reason behind this isn't entirely apparent, but researchers believe that spironolactone or its metabolites might directly impact the ovaries. This could disrupt the normal cycle of estrogen and progesterone production, leading to irregular menstrual cycles and other hormonal imbalances. It's a bit of a risk for us, given we already have imbalances. If I have regular periods, my main worry would be how it will affect my period and my fertility. If you consider conceiving, I wouldn’t risk taking this medication due to its effect on our hormones.
In terms of research, a study examined 25 women (13 lean and 12 overweight) who received oral spironolactone (100 mg/day) for 12 months. Overweight women were also recommended to eat a low-calorie diet. The most notable differences after treatment were a significant reduction in hirsutism in both groups, a significant decrease in triglycerides in overweight women, and a significant increase in HDL cholesterol in lean women. Furthermore, overweight women who experienced weight loss showed substantial improvements in insulin levels and insulin resistance. In contrast, despite spironolactone treatment, those who did not lose weight did not show these improvements. It shows again that weight loss creates change. Regarding acne, it was noted in 8 out of the 25 subjects, and 4 of them got better, so a 50% success rate.
What about blood pressure?
Given the main effect of the medication is to lower aldosterone, what consequences can that have?
There is a risk of hyperkalemia: dangerously high potassium levels, which can be life-threatening if not monitored and fluid and electrolyte imbalance, which can lead to symptoms like extreme weakness and dizziness.
A retrospective analysis of adverse events reported with spironolactone between January 1, 1969, and December 30, 2018, found that Hyperkalemia made up 16.1% of all adverse events. Still, it was uncommon in women aged ≤45 years (1.9% of all hyperkalemia cases). This is a percentage of the adverse effects logged, not that it happens for 16% of people taking it. I just want to make sure that is clear.
Will it help my PCOS?
Some studies investigate the use of Spironolactone with Metformin. A pilot study by Long et al. (2022) looked at the effects of low-dose spironolactone combined with metformin compared to either drug alone on insulin resistance (IR). The study found that the combined therapy decreased HOMA-IR to a greater extent than metformin or spironolactone alone.
Other studies are currently ongoing, looking into Spironolactone with cyclic progesterone, pioglitazone and Metformin. It seems the research specifically done in our condition is immature.
Conclusion
The decision of whether this medication is worth taking is one that needs to be made by you and your doctor. My honest advice is to understand the side effects in detail, check that you don’t have a family history of kidney disease, and make a plan with your doctor to check certain markers periodically to ensure that it is not having a negative impact on other parts of the body.
My other advice is to figure out how to lower androgens through diet, supplements, and exercise. I wish there were a bullet solution, but there isn’t.
Lastly, please don’t be ashamed or fearful to take medication. It is ok to want a break from the tiring symptoms of PCOS. Getting to the root cause is essential but sometimes our body might just need a break.
See you next Sunday,
Francesca
References
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. https://doi.org/10.1530/EJE-17-0516
Armanini, D., Andrisani, A., Bordin, L., & Sabbadin, C. (2016). Spironolactone in the treatment of polycystic ovary syndrome. Expert Opinion on Pharmacotherapy, 17(13), 1713–1715. https://doi.org/10.1080/14656566.2016.1215430
Armanini, D., Castello, R., Scaroni, C., Bonanni, G., Faccini, G., Pellati, D., Bertoldo, A., Fiore, C., & Moghetti, P. (2007). Treatment of polycystic ovary syndrome with spironolactone plus licorice. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 131(1), 61–67. https://doi.org/10.1016/j.ejogrb.2006.10.013
Barbieri, J. S. (2023). Temporal trends in the use of systemic medications for acne from 2017 to 2020. JAMA Dermatology (Chicago, Ill.), 159(10), 1135–1136. https://doi.org/10.1001/jamadermatol.2023.2363
Efficacy of Spironolactone Compared with Doxycycline in Mode-rate Acne in Adult Females: Results of the Multicentre, Controlled,Randomized, Double-blind Prospective and Parallel Female AcneSpironolactone vs doxyCycline Efficacy (FASCE) Study. (n.d.).
Ganie, M. A., Khurana, M. L., Nisar, S., Shah, P. A., Shah, Z. A., Kulshrestha, B., Gupta, N., Zargar, M. A., Wani, T. A., Mudasir, S., Mir, F. A., & Taing, S. (2013). Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study. The Journal of Clinical Endocrinology and Metabolism, 98(9), 3599–3607. https://doi.org/10.1210/jc.2013-1040
Long, T., Zhang, Y., & Zheng, S. (2022). Effects of low-dose spironolactone combined with metformin on insulin resistance and functional improvement in polycystic ovary syndrome: A 12-week pilot study. International Journal of Endocrinology.
O’Brien, R. C., Cooper, M. E., Murray, R. M., Seeman, E., Thomas, A. K., & Jerums, G. (1991). Comparison of sequential cyproterone acetate/estrogen versus spironolactone/oral contraceptive in the treatment of hirsutism. The Journal of Clinical Endocrinology and Metabolism, 72(5), 1008–1013. https://doi.org/10.1210/jcem-72-5-1008
Rani, N., Kumar, P., Mishra, A. K., Sankuratri, B. Y. V., Sethi, S., Gelada, K., & Tiwari, H. (2021). Efficacy of spironolactone in adult acne in polycystic ovary syndrome patients an original research. Journal of Pharmacy & Bioallied Sciences, 13(Suppl 2), S1659–S1663. https://doi.org/10.4103/jpbs.jpbs_391_21
Santer, M., Lawrence, M., Renz, S., Eminton, Z., Stuart, B., Sach, T. H., Pyne, S., Ridd, M. J., Francis, N., Soulsby, I., Thomas, K., Permyakova, N., Little, P., Muller, I., Nuttall, J., Griffiths, G., Thomas, K. S., Layton, A. M., & SAFA trial investigators. (2023). Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ (Clinical Research Ed.), 381, e074349. https://doi.org/10.1136/bmj-2022-074349
Studen, K. B., Sebestjen, M., Pfeifer, M., & Prezelj, J. (2011). Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome. European Journal of Endocrinology, 164(3), 389–395. https://doi.org/10.1530/EJE-10-0709
We are all unique in our ways, so this information is for educational purposes only. In my communications, I summarise research data and bring my experience. This shouldn’t be viewed as medical advice at any point. Please consult your healthcare provider further about your health needs.