From the Guidelines
Divalproex sodium may potentially reduce follicular reserve in a 35-year-old female due to its association with reproductive endocrine disorders, including polycystic ovary syndrome (PCOS) and hormonal imbalances, as suggested by studies such as 1. The medication's impact on follicular reserve is a concern because, at age 35, a woman's follicular reserve is already naturally declining. Divalproex might accelerate this process through disruption of normal hormonal pathways, altering hormone metabolism, and increasing androgen levels, which could affect follicular development and ovulation 1. Key points to consider include:
- The potential for divalproex to cause weight gain, which can have direct negative effects on health and life expectancy, and may trigger the manifestation of endocrine disorders such as PCOS in predisposed women 1.
- The direct effects of antiepileptic drugs, including valproate, on peripheral female endocrine glands, which have been shown in animal models to alter steroidogenesis and increase testosterone to oestradiol ratios 1.
- The importance of discussing fertility preservation concerns with both a neurologist and reproductive endocrinologist, and considering regular monitoring of reproductive hormones (FSH, AMH, estradiol) to track any changes to ovarian reserve. Given the potential risks, it is crucial for women taking divalproex to be aware of these possible effects and to discuss their individual situation with healthcare professionals to make informed decisions about their treatment and reproductive health.
From the Research
Impact on Follicular Reserve
The impact of divalproex on follicular reserve in a 35-year-old female is a concern due to the potential effects of valproate on ovarian function and folliculogenesis.
- A study published in 2019 2 found that chronic valproate treatment in adult female albino rats led to a significant decrease in the number of follicles and an increase in atretic follicles.
- The same study found that folic acid supplementation can modulate ovarian follicular and hormonal disturbances induced by valproate, suggesting a potential protective effect.
- Another study published in 2009 3 investigated the effect of valproate on serum levels in women with epilepsy and found that valproate levels were lower during the active phase of combined oral contraceptive use.
- However, this study did not directly address the impact of valproate on follicular reserve.
Hormonal Effects
Valproate has been shown to affect reproductive hormones, including a significant increase in testosterone levels and a decrease in estradiol, progesterone, FSH, and LH levels 2.
- A study published in 1982 4 found that sodium valproate decreased prolactin secretion in normal and hyperprolactinemic subjects, suggesting an inhibitory effect on prolactin release.
- The clinical significance of these hormonal changes on follicular reserve is not fully understood and requires further investigation.
Clinical Considerations
Women of childbearing age taking valproate should be informed about the potential risks and benefits of treatment, including the impact on follicular reserve and reproductive health 5.
- A study published in 2020 5 found that women taking valproate were better informed about the risks involved with treatment, but still required more information about the use of folic acid and contraception.
- The use of valproate in women of childbearing age should be carefully considered, and alternative treatment options should be explored when possible.