Does a patient with Polycystic Ovary Syndrome (PCOS) and hirsutism benefit from Spironolactone (Aldactone) and Norethisterone (Primolut)?

From the Guidelines

A patient with PCOS and hirsutism may benefit from treatment with spironolactone (Aldactone) and norethisterone (Primolut), as this combination has been shown to effectively address the hormonal imbalance and visible manifestation of hirsutism. Spironolactone is typically started at 50-100mg daily and can be increased to 200mg daily if needed, taken in divided doses, as supported by a recent study published in the Journal of the American Academy of Dermatology 1. Norethisterone is usually prescribed at 5-10mg daily for 10-14 days each month. This combination works because spironolactone blocks androgen receptors and reduces testosterone production, directly addressing the excess androgen that causes hirsutism, as explained in the guidelines for the management of acne vulgaris 1. Norethisterone, a progestin, helps regulate menstrual cycles and provides endometrial protection.

Patients should be aware that visible improvement in hirsutism typically takes 3-6 months of consistent treatment. Spironolactone requires monitoring of potassium levels and is contraindicated in pregnancy due to potential feminization of male fetuses, so effective contraception is essential during treatment, as noted in the study 1. Side effects may include irregular menstrual bleeding, breast tenderness, and fatigue. This combination therapy addresses both the hormonal imbalance of PCOS and its visible manifestation as hirsutism. The American College of Obstetricians and Gynecologists (ACOG) also recommends the use of combination oral contraceptive pills for the long-term management of PCOS, which can help suppress androgen secretion and increase circulating sex hormone binding globulin 1. Additionally, the ACOG suggests that the primary treatment for hirsutism in PCOS is often palliative rather than curative, and that agents such as oral contraceptives, antiandrogen drugs, and insulin-sensitizing agents may be used to manage hirsutism 1.

Some key points to consider when treating a patient with PCOS and hirsutism with spironolactone and norethisterone include:

• Monitoring potassium levels to avoid hyperkalemia
• Using effective contraception to prevent pregnancy due to the potential feminization of male fetuses
• Regulating menstrual cycles and providing endometrial protection with norethisterone
• Addressing the hormonal imbalance and visible manifestation of hirsutism with spironolactone
• Being aware of potential side effects such as irregular menstrual bleeding, breast tenderness, and fatigue.

From the Research

Treatment Options for PCOS and Hirsutism

• The use of spironolactone, also known as aldactone, has been studied as a treatment for hirsutism in women with polycystic ovary syndrome (PCOS) 2, 3, 4, 5.
• Research suggests that spironolactone can be effective in reducing hirsutism in women with PCOS, with studies showing a significant reduction in Ferriman-Gallwey score and hirsutism score 2, 3, 4.
• The addition of low-dose spironolactone to metformin therapy has been shown to induce a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone 4.
• Primolut, which contains norethindrone, is a progestin that can be used to treat hirsutism in women with PCOS, but its effectiveness compared to spironolactone is not well established in the provided studies.

Efficacy of Spironolactone

• A study published in 1993 found that low-dose spironolactone (50 mg or 75 mg daily) resulted in an excellent clinical response in 61% of women with hyperandrogenism, including those with PCOS 2.
• A systematic review and meta-analysis published in 2023 found that spironolactone exhibited a significant reduction in Ferriman-Gallwey score in idiopathic hirsutism compared to finasteride and cyproterone acetate 3.
• Another study published in 2014 found that the addition of low-dose spironolactone to metformin therapy resulted in a more marked reduction of clinical and biochemical hyperandrogenism than metformin alone 4.

Side Effects and Tolerability

• The main side effects reported with spironolactone use in women with PCOS and hirsutism include menstrual irregularity, mild nausea, vomiting, and diarrhea 3, 4.
• Spironolactone is generally well tolerated in women with PCOS and hirsutism, with few patients discontinuing treatment due to side effects 2, 3, 4.