The Hemp Connection [Search results for valproic acid] 

It came up in a Facebook conversation yesterday that a woman with PCOS had been prescribed Depakote (valproic acid) and her PCOS became worse.

It is important to know that this medication, commonly administered for the treatment of bipolar disorder and epilepsy, has actually been reported in several research studies to worsen laboratory values and symptoms of PCOS (see references below).

There is speculation that this is partially due to the fact that carnitine levels drop in the presence of Depakote.

The good news is, carnitine is available as an over the counter supplement, and research has suggested that taking acetyl-l-carnitine supplements while on valproic acid is beneficial to help minimize these side effects. The dose that has been reported/suggested is 4 grams per day.

Even though the research isn't as strong for other psych meds that have been correlated with weight gain, it's in my tool box to recommend to anyone who has noticed their symptoms worsen after starting medications in this category (psych and nervous system medications), to use the carnitine supplements.

I have written in other places that I believe it should be standard protocol when prescribing Depakote, to also prescribe carnitine. I hope, at least in practices where women with PCOS are part of the specialty, that this can become part of the treatment plan. It's an easy tool with a lot of potential.

Popovic V, Spremovic S. The effect of sodium valproate on luteinizing hormone secretion in women with polycystic ovary disease. J Endocrinol Invest. 1995 Feb;18(2):104-8.

Stephen LJ, Kwan P, Shapiro D, Dominiczak M, Brodie MJ. Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Epilepsia. 2001 Aug;42(8):1002-6.

Luef G, Abraham I, Trinka E, Alge A, Windisch J, Daxenbichler G, Unterberger I, Seppi K, Lechleitner M, Krämer G, Bauer G. Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Res. 2002 Jan;48(1-2):91-102.

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Kennedy SH. Valproate, bipolar disorder and polycystic ovarian syndrome. Bipolar Disord. 2003 Feb;5(1):28-35.

Ribacoba-Montero R, Martínez-Faedo C, Díaz-Díaz C, Salas-Puig J. [Remission of polycystic ovary syndrome associated with valproic acid in an epileptic female] [Article in Spanish] Rev Neurol. 2003 Apr 1-15;36(7):639-42.

Betts T, Yarrow H, Dutton N, Greenhill L, Rolfe T. A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy. Seizure. 2003 Sep;12(6):323-9.

Wood JR, Nelson-Degrave VL, Jansen E, McAllister JM, Mosselman S, Strauss JF 3rd. Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects. Physiol Genomics. 2005 Feb 10;20(3):233-43. Epub 2004 Dec 14.

Flück CE, Yaworsky DC, Miller WL. Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2. Epilepsia. 2005 Mar;46(3):444-8

Rasgon NL, Altshuler LL, Fairbanks L, Elman S, Bitran J, Labarca R, Saad M, Kupka R, Nolen WA, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Leverich G, Grunze H, Walden J, Post R, Mintz J. Reproductive function and risk for PCOS in women treated for bipolar disorder. Bipolar Disord. 2005 Jun;7(3):246-59.

Morris GL 3rd, Vanderkolk C. Human sexuality, sex hormones, and epilepsy. Epilepsy Behav. 2005 Dec;7 Suppl 2:S22-8. Epub 2005 Oct 20.

Joffe H, Cohen LS, Suppes T, McLaughlin WL, Lavori P, Adams JM, Hwang CH, Hall JE, Sachs GS. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry. 2006 Jun 1;59(11):1078-86. Epub 2006 Jan 31.

Joffe H, Cohen LS, Suppes T, Hwang CH, Molay F, Adams JM, Sachs GS, Hall JE. Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report. Biol Psychiatry. 2006 Dec 15;60(12):1378-81. Epub 2006 Sep 1.

Prabhakar S, Sahota P, Kharbanda PS, Siali R, Jain V, Lal V, Khurana D. Sodium valproate, hyperandrogenism and altered ovarian function in Indian women with epilepsy: a prospective study. Epilepsia. 2007 Jul;48(7):1371-7. Epub 2007 Apr 18.

Reynolds MF, Sisk EC, Rasgon NL. Valproate and neuroendocrine changes in relation to women treated for epilepsy and bipolar disorder: a review. Curr Med Chem. 2007;14(26):2799-812.

Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, Warnock CR, Isojärvi J. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol. 2008 Aug;64(2):200-11.

Bilo L, Meo R. Polycystic ovary syndrome in women using valproate: a review. Gynecol Endocrinol. 2008 Oct;24(10):562-70.

Gorkemli H, Genc BO, Dogan EA, Genc E, Ozdemir S. Long-term effects of valproic acid on reproductive endocrine functions in Turkish women with epilepsy. Gynecol Obstet Invest. 2009;67(4):223-7. Epub 2009 Feb 24.

I was recently asked my opinion about whether or not biotin supplementation would help hair loss. Here's a bit of commentary, plus information about melatonin, another supplement that has been studied.

As with any supplement, it's only going to help if you are indeed deficient in that particular nutrient. There are many reasons you could be deficient in biotin. One of the most relevant to PCOS, is the use of medications valproic acid and carbamazepine. These are seizure medications, also used to treat bipolar disorder and migraine headaches, that have been reported to cause or exacerbate PCOS. So if you've ever been on those medications, you may want to consider supplementation.

If your diet has been out of balance in any way (severe dieting, overeating, eating disorder, cutting out entire categories of food (gluten-free, paleo, vegan, etc.) with a focus on what to eliminate rather than on how to be complete, you may be at risk for biotin deficiency.

It's certainly not going to hurt, and it might help. The dose reported in the literature is 5 to 10 mg per day. However, keep in mind, if your hair loss is primarily related to high testosterone levels and you do not adhere to your complete recommended protocol, biotin will not fix what those problems are causing. It's not a miracle cure.

The best food source of biotin is Swiss chard. Which I was happy about because one of my favorite quick meals is a Swiss chard frittata…I actually planned on making one tonight before knowing this. Nice coincidence!

The other supplement I'm a little more versed in, is melatonin. You all know I'm a big fan of sleep, almost more than diet, for its power to heal. About a year ago, I was poking around in PubMed and found the abstract below, specifically looking at using melatonin to treat androgenic alopecia, which is specifically the type of hair loss you all have. I was coming out of a pretty stressful personal period myself, and had started to notice that my hairline was receding…not fun to look at! So I figured I'd try it myself before writing about it. What I do, is take a melatonin pill, dissolve it in my hand with a few drops of water, and then massage it into my skin with coconut oil. Simply using water didn't work, it needed a carrier. I've noticed that my hair is gradually starting to grow in again. It's not thick and lush, by any means, but it IS growing some hair back.

A caveat here, it won't happen in a week, and you have to be consistent with application. If you're going to flake out about it…don't bother even starting. It's taken almost a year to see a difference. But if you're committed and willing to be persistent, it's definitely worth a try.

Here's the article.
Fischer TW, Burmeister G, Schmidt HW, Elsner P. Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial. Br J Dermatol. 2004 Feb;150(2):341-5.

BACKGROUND: In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far.

OBJECTIVES: To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss.
METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period.

RESULTS: Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo (n=12; P=0.012). For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia (n=28; P=0.046). The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak.

CONCLUSIONS: To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.

Castro-Gag M, Pérez-Gay L, Gómez-Lado C, Castiñeiras-Ramos DE, Otero-Martínez S, Rodríguez-Segade S. The influence of valproic Acid and carbamazepine treatment on serum biotin and zinc levels and on biotinidase activity. J Child Neurol. 2011 Dec;26(12):1522-4. Epub 2011 Jun 3.

Wolf B. EditorsIn: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. Biotinidase Deficiency. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2000 Mar 24 [updated 2011 Mar 15].

Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008 Nov 1;3(6):715-724.