Isotretinoin has an impact on testosterone levels and other hormones, which have secondary effects on the body, along with the mucous membranes like the vagina and urinary tract. While the treatment is to improve skin, it also creates skin fragility and other issues, particularly around the vagina and anal area.
There is a growing movement from young people taking isotretinoin (Accutane) reporting side effects that include ongoing sexual dysfunction years after they stopped treatment. Sexual side-effects are NOT listed as a complication of this drug, but part of how it works is by affecting hormones like testosterone.
Side effects of isotretinoin
Isotretinoin is known for some serious and sometimes severe side effects. These impacts limit its use, but the drug is still widely prescribed to young people globally due to a lack of other options for severe acne.
The known side effects of isotretinoin include birth defects, thus the birth control pill is often prescribed to avoid accidental pregnancy.
Impacts of this drug include fragile skin, mood changes, fatigue, eczema, nose bleeds, muscle aches, eye problems, infections, and others, but it might not stop there.
Other severe side effects can include anxiety, fatigue, and an inability to feel pleasure. Those with vaginas may experience dryness, painful sex, loss of libido, numbness and the inability to orgasm, with a loss of periods, ovulation and fertility. Yeast infections are more likely.
A survey1 amongst 50 female patients found 32 per cent experienced vaginal dryness, 22 per cent reported vulvar discomfort, 20 per cent had painful sex, 10 per cent reported cuts and tears (fissures), and 24 per cent had a new or increased need for lubricant.
Others reported perianal dermatitis, fissures and bleeding. Higher doses saw worse effects. The skin barrier is one of the most important factors in our protection against invading microbes, so skin fragility is a huge issue and contributes to infections in people using isotretinoin2.
Side effects in those with a penis include low libido, erectile dysfunction, impotence, numbness, inability to orgasm, changes to ejaculate fluid, shrinkage of the penis and a lack of blood flow to erectile tissue. Undesirable breast tissue development may also occur3. Sexual desire and function can be completely wiped out.
Some side-effects do not respond to treatment, nor improve with time, while others clear up once treatment is finished. The longevity of some side effects, particularly sexual side effects, is a very serious and lifelong issue for those affected. The problems do not respond to any treatments and appear to be permanent. Remember, no sexual side effects are listed in the warnings.
A Spanish study4 found that six out of 30 patients taking isotretinoin developed erectile dysfunction (ED) during the study, versus two in the control group. Twelve out of 20 taking isotretinoin developed depression, versus three in the control group. There are several other studies on the side effects5,6 and sexual side effects4,7 of this drug.
Why do long-term side effects occur?
We don’t know for sure, but one theory as to why some drugs cause long-term side-effects revolves around epigenetic changes to DNA expression.
These changes may be caused by an indirectly acting drug like isotretinoin. Isotretinoin has transcription factor activity, meaning it can alter transcription factor activity at gene promoters, resulting in the altered expression of receptors, signalling molecules and other proteins that can alter genetic regulatory circuits. Meaning, the drug can permanently alter the instructions a gene gives to the body.
When the drug is taken for an extended period of time, cells adapt, with more permanent modifications to DNA methylation and chromatin structure, ongoing. This process is what can cause a drug’s effects to continue on even after the drug is stopped.
This epigenetic hypothesis could explain many other conditions that occur post-treatment such as tardive dyskinesia or drug-induced systemic lupus erythematosus (SLE).
The authors of this hypothesis8 say:
If this hypothesis is correct the consequences for modern medicine are profound, since it would imply that our current understanding of pharmacology is an oversimplification.
We propose that epigenetic side-effects of pharmaceuticals may be involved in the etiology of heart disease, cancer, neurological and cognitive disorders, obesity, diabetes, infertility, and sexual dysfunction.
Understanding how isotretinoin works
Isotretinoin is a drug used to treat cystic acne that works to reduce androgens, to damage or dry up oil glands in the skin to stop sebum production that drives acne. Androgens directly stimulate oil glands in the skin. More oil means more acne.
Isotretinoin impacts other areas of the body including mucous membranes – found all over, but in particular the vagina, urinary tract, digestive tract and respiratory tract.
The impact of isotretinoin on hormones
In research, we’ve seen how isotretinoin affects hormones. It is understood the drug inhibits 5-a-reductase, which ultimately increases the conversion of testosterone to oestrogen, thus lowering testosterone levels and increasing oestrogen levels.
In one study9 looking into those on three months of the drug, testosterone and leutinising hormone (LH) levels were both decreased.
In another study10, androstenedion was reduced after 12 weeks of treatment. This drug robs the body of testosterone, increasing the impacts of oestrogen, particularly in the male body.
What to do if you think you’ve been affected by isotretinoin
We recommend you visit Risk, an advocacy website, for further reading and more information.
References
- 1.Cunningham L, Menzies S, Moore E, Shudell E, Moloney FJ, Ralph N. Mucocutaneous adverse effects of the genital and perianal skin from isotretinoin therapy. Journal of the American Academy of Dermatology. Published online October 2020:1174-1175. doi:10.1016/j.jaad.2020.01.071
- 2.Graham M, Corey R, Califf R, Phillips H. Isotretinoin and Staphylococcus aureus infection. A possible association. Arch Dermatol. 1986;122(7):815-817. https://www.ncbi.nlm.nih.gov/pubmed/3460532
- 3.Ustun I, Rifaioglu EN, Sen BB, Inam MU, Gokce C. Gynecomastia: a rare complication of isoretinoin? Cutaneous and Ocular Toxicology. Published online July 20, 2012:93-94. doi:10.3109/15569527.2012.705406
- 4.Tirado Sánchez A, León Dorantes G. Disfunción eréctil durante el tratamiento con isotretinoína. Actas Urológicas Españolas. Published online January 2005:974-976. doi:10.1016/s0210-4806(05)73379-9
- 5.Rademaker M. Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin. Australasian Journal of Dermatology. Published online November 2010:248-253. doi:10.1111/j.1440-0960.2010.00657.x
- 6.Hanson N, Leachman S. Safety issues in isotretinoin therapy. Seminars in Cutaneous Medicine and Surgery. Published online September 2001:166-183. doi:10.1053/sder.2001.28209
- 7.Rossi M, Pellegrino M. Acitretin-associated erectile dysfunction: a case report. Cases Journal. Published online November 19, 2009. doi:10.1186/1757-1626-2-210
- 8.Csoka AB, Szyf M. Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology. Medical Hypotheses. Published online November 2009:770-780. doi:10.1016/j.mehy.2008.10.039
- 9.Karadag A, Ertugrul D, Tutal E, Akin K. Isotretinoin Influences Pituitary Hormone Levels in Acne Patients. Acta Derm Venerol. Published online 2011:31-34. doi:10.2340/00015555-1013
- 10.Palatsi R, Ruokonen A, Oikarinen A. Isotretinoin, tetracycline and circulating hormones in acne. Acta Derm Venereol. 1997;77(5):394-396. doi:10.2340/0001555577394396
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