Prasterone for vulvar and vaginal atrophy in postmenopausal women

Approved indication: moderate to severe symptoms of vulvar and vaginal atrophy in postmenopausal women
Intrarosa (Theramex)
6.5 mg pessaries

After menopause the effects of the lack of estrogen include changes in the genitourinary tract. In the vagina the epithelium becomes thinner and the pH becomes less acidic. Vulvovaginal atrophy may lead to symptoms such as dryness, itching and dyspareunia. The severity of the symptoms helps guide treatment choice.

One treatment option is applying a topical estrogen, such as estradiol. Prasterone is a new topical treatment for vaginal symptoms that is a steroid precursor of estrogen. It is identical to human dehydroepiandrosterone. After intravaginal application, the vaginal cells convert prasterone to estrogens and androgens. This increases the number of vaginal cells and reduces the vaginal pH. Although some prasterone is absorbed systemically and metabolised into estradiol and testosterone, their concentrations remain within the normal ranges for postmenopausal women.

The approval of intravaginal prasterone for postmenopausal women with moderate to severe symptoms of vulvovaginal atrophy is mainly based on 3 randomised double-blind efficacy trials.¹ In these trials, 436 women inserted a vaginal pessary containing 6.5 mg prasterone nightly for 12 weeks. Another group of 260 women inserted a placebo. Treatment resulted in a statistically significant change in vaginal histology and decrease in vaginal pH (0.72 units) compared with placebo. Severity scores for dyspareunia, the most bothersome baseline symptom, decreased in all 3 trials. On a 4-point scale, treatment reduced the severity of dyspareunia by 0.46 points compared with placebo. There was also a reduction in vaginal dryness compared with placebo.¹ Longer-term benefit of prasterone on female sexual function in a number of domains (including lubrication and pain) was reported in an open-label safety study, which treated 154 postmenopausal women for 52 weeks.²

Although smaller concentrations of hormones enter the circulation than with systemic menopausal hormone therapy, prasterone is contraindicated in women with a history of breast cancer or thromboembolism.³ While endometrial hyperplasia did not occur in the clinical trials, any postmenopausal bleeding requires investigation.³ Some women developed abnormal cervical cytology during the 52-week open-label safety study.²

Most adverse events occurred at a similar frequency in the prasterone and placebo groups. More women in the prasterone group reported vaginal discharge than in the placebo group (8.3% versus 3.4%), but this could be partly related to the vehicle used in the prasterone formulation.¹ Treatment does not need to be ceased if vaginal discharge occurs and very few women in the efficacy studies discontinued prasterone because of this effect.¹ The formulation can also weaken the latex used in barrier methods such as condoms, which may still be required in postmenopausal women for prevention of sexually transmitted infections.

Although prasterone has statistical superiority, its advantage over placebo for symptom relief appears modest. A comparison with other studies suggests that 6.5 mg prasterone may have similar efficacy to 10 micrograms intravaginal estradiol.⁴ The need to continue treatment, taking into account potential benefits and harms, should be reviewed at least every 6 months.³

This new drug comment was finalised on 9 September 2024.

🅃 manufacturer provided the AusPAR and the product information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about this drug was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Labrie F, Archer DF, Martel C, Vaillancourt M, Montesino M. Combined data of intravaginal prasterone against vulvovaginal atrophy of menopause. Menopause 2017;24:1246-56.
2. Bouchard C, Labrie F, Derogatis L, Girard G, Ayotte N, Gallagher J, et al. Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study. Horm Mol Biol Clin Investig 2016;25:181-90.
3. Therapeutic Goods Administration. Australian Product Information - INTRAROSA prasterone 6.5 mg pessary blister pack. Department of Health and Aged Care; 2023. [cited 2024 Sep 10]
4. Archer DF, Labrie F, Montesino M, Martel C. Comparison of intravaginal 6.5mg (0.50%) prasterone, 0.3mg conjugated estrogens and 10mug estradiol on symptoms of vulvovaginal atrophy. J Steroid Biochem Mol Biol 2017;174:1-8.

 The new drug commentaries in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.