Oral contraception in MS

Eur J Obstet Gynecol Reprod Biol. 2015 Oct;193:1-4. doi: 10.1016/j.ejogrb.2015.06.030. Epub 2015 Jul 9.

Symptoms of multiple sclerosis during use of combined hormonal contraception.

Kempe P, Hammar M, Brynhildsen J.

OBJECTIVE: The incidence and disease course of multiple sclerosis (MS) is influenced by sex steroids, and several studies have shown less disease activity during high estrogen states. We have previously shown variation in symptom experience related to the estrogen/progestogen phase in women using combined hormonal contraceptives (CHC) in a small sample. The aim of this study was to confirm these results in a larger sample.

STUDY DESIGN: Self-assessment of symptoms of MS in relation to CHC cycle by 22 female MS patients. A symptom diary based on a validated instrument for cyclical symptoms was used. Mean symptom scores for high and low estrogen/progestogen phases were compared.

RESULTS: The women scored four out of ten symptoms significantly higher during the pill-free week than during the CHC phase (p<.05).

CONCLUSION: Women with MS report more pronounced symptoms during the pill-free, low-estrogen/progestogen phase of CHC use. Future studies should investigate, with a prospective, controlled design, the effects that continuous-use regimens of CHC have in women with MS.

Hormonal Contraceptives and Multiple Sclerosis Susceptibility (S34.003)

Kerstin Hellwig, Lie Chen and Annette Langer-Gould
Published online before print April 8, 2015 Neurology April 8, 2014 vol. 82 no. 10 Supplement S34.003 

OBJECTIVE: To determine whether contemporary hormonal contraceptives (HC) use increases the risk of MS

BACKGROUND: Whether use of contemporary HCs contributes to the rising incidence of multiple sclerosis (MS) in women is unclear.

DESIGN/METHODS: We conducted a population-based nested case-control study from the membership of Kaiser Permanente Southern California (KPSC). We identified females ages 14-48 years with incident MS or it’s precursor-clinically isolated syndrome (CIS) between 2008 and 2011, who had at least 3 years of continuous membership prior to symptom onset. Ten controls per case were matched on age, race/ethnicity and membership characteristics. Data were obtained from the complete electronic health record and analyzed using conditional logistic regression, adjusted for smoking and live births 3 yrs prior to symptom onset.

RESULTS: We identified 305 incident female cases with MS/CIS and 3050 matched-controls. 29.2% of cases and 23.5% of controls had used a HC for at least 3 months within the 3 years prior to symptom onset. The majority used estrogen/progestin combination preparations. Women that used any hormonal contraceptive in the 3 years prior to symptoms onset, and particularly those that had stopped at least 1 month prior to symptom onset, had a slightly increased risk of MS/CIS (ever-users adjusted OR=1.35, 95%CI=1.01-1.80, p=0.04; not current users adjusted OR=1.50, 95%CI=1.05-2.14, p=0.026).

CONCLUSIONS: Our findings suggest that use of modern hormonal contraceptives may be contributing at least in part to the rise in incidence of MS in women.

Following on from my last weeks post on improving your MS outcomes by tackling obesity, one topic which as a woman I feel requires further exploration is the non-contraceptive effect of the pill on MS. To say the least, the evidence is conflicting. 
The oestrogen used in contraceptive pills is 100-500x more potent than what is naturally produced by our ovaries. Therefore, the effects of oestrogen will be more evident in the combined pill.
Studies have reported lower incidence of MS in those on the combined pill than non-users, whilst women using the pill after diagnosis had a more benign disease course than those who did not. Along the same lines, age of onset of MS symptoms is pushed back following use (onset of 31 years versus 33 years who used contraception), and the years increased based on the duration of intake (24 years old with less than an year of use versus 31 years with more than 10 years use). Above, the first abstract, is a more prospective assessment of MS symptoms on the pill and they found that women on the pill had greater symptoms during the low-oestrogen phase (i.e. over the pill free days 22-28); including vertigo, weakness, urinary symptoms, stiffness and numbness.

Then there is the opposite, the second abstract hints at increased risk of MS/CIS in women who have been on the pill; amounting to roughly 35% even after adjusting for smoking and pregnancy. This increases to 50% in those who stopped 1 month prior to first symptoms. In a follow up study Annette Langer-Gould found that products containing levonogesterol increased the risk by an odds ratio of 1.75 (95% CI 1.29-2.37), while those containing norethindrone increased the risk by an odds of 1.57 (95% CI 1.16-2.12). But it can be argued that in absolute numbers the risk doesn’t amount to much owing to the rarity of the disease. In another study from Belgium, involving 973 women with MS, in a subgroup who were progressive onset, oral contraceptive use was associated with a higher risk of reaching EDSS 6 (i.e. the requirement for a walking stick).

This ambiguity over the unknown effects of oral contraceptives will therefore mean that there will be hesitation from prescribers in women with MS than without.

About the author

Neuro Doc Gnanapavan


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  • I've wondered if a diet high in soya might have some impact on MS in some way. Many of soy’s health benefits have been linked to isoflavones—plant compounds that mimic estrogen.

    • Phytoestrogens from plants have been postulated to have neuroprotective effects in animal models for AD, stroke etc. But there are no human studies – diet is very difficult to control for. A study using oestrogen alone in postmenopausal women was abandoned owing to an increased stroke risk: S. Wassertheil-Smoller, S.L. Hendrix, M. Limacher, G. Heiss, C. Kooperberg, A. Baird, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial JAMA, 289 (2003), pp. 2673–2684.

  • Wow!!! NDGthank you very much for publishing!!!

    I so far haven't decided what to do, whether or not return for the oral contraceptive.
    Perhaps return to a combination of low-dose estrogen/progesterone as it was my last.

    The purpose this last Belgian study that you mentioned which type of oral contraceptive was used more by women participating in the survey?

    • Unfortunately the type of oral contraceptive is not defined in the study. They simple say: "A shorter time to EDSS 6 was found in users of oral contraception, especially when they started as a teenager".

    • NDG was thinking here to read the publication, is that some of the negative studies on oral contraceptives in MS should be a 'dependency' that the body ends up taking estrogen?

      Another thing: in the case of NuvaRing (vaginal ring) it is formulated with combined estrogen to with etonogestrel – derivative of desogestrel, a recent synthetic progesterone second generation. Would I have or not the greatest risk of progression of MS by just levonogestrol is in the group, since it acts by changing the cervical mucus?

      In a recent study I published here on the blog it appears that the combined use of Trimestra + Copaxone had no effect on the RRMS in women…

    • In answer to your first part, oestrogen levels in women is within normal fluctuations through life (i.e. not deficient), but drops dramatically after pregnancy – may explain the susceptibility to relapse, in addition to the loss of immunosuppressive effects of pregnancy (also increases during pregnancy), and also in the post-menopausal period with some linking this to progression in EDSS.

      Most contraception is a combination of oestrogen and progesterone, levonogestrol is also a progestin. I don't think the delivery device matters much.

      The trial with oestrogen on top of copaxone is different from the other studies in that it's a randomised control trial, and although the relapse rate in the oestrogen group was down it was not statistically different from placebo. It is one trial and needs to be repeated as there are ongoing publications from cohort studies (ones above) suggesting that there may be something there!

  • I was on a combined pill for several years, I came off it and then my first MS symptom showed under a year later.

    I'm not saying it was the cause of my MS though. May be the pill was delaying progression and keeping my MS very benign. I don't think I would want to go back on contraceptives unless more studies are done.

  • My sister has MS for 3 yrs now. From that time she definately left contraceptive after 6 yrs. After this left she experienced secunder amennorhea, and weight gain, and diagnosed insulin resistancy, and thyroid impflamation. Now she take syntroxine, and merckformin daily, her weight have been normal, but her secunder amennorhea remained. From last june her MS seems to be so progressive, after 2 clinical brainstem flares (double vision, mild swll probl., and finally INO, with balance issuse) which completley dissapeared (03/2014;10/2014) she experiencing slightly worsening ponto-cerebellar sympthoms (double vision, ataxia). Her last MR showed enlarging confluated T2 hyper- and T1 mild hypointense lesions on her ponto-cerebellar area. So last week she have been changed from Tec (only for 6mnths) to Gilenya. Beforehand she shots copaxone for 15 mnths.
    In her current state what can we do? Deal with only her MS (try to stabilize) or try to help the other problems too. (Maybe the other problems related with her MS….) Does she use contraceptives again. If she does which is the best…
    This is a so complicated situation, and I'm afraid nobody knows the best answer.

  • A study of risk factors for acquisition of Epstein-Barr virus and its subtypes.


    "EBV infection Risk was lower (1) among students who always used a condom than among those who had sexual intercourse without one and (2) among female oral-contraceptive users than among sexually active nonusers."

  • I've never used oral contraception. Should I start to given this research? Anything to increase my odds of a more milder disease course..

    • This is difficult to answer, I have presented what is out there in terms of the research. It will be up to you to decide whether this is what you want to do. I also advice that you look up the side effects beforehand also.

  • I was diagnosed with MS at age 28, I had one major episode requiring a lumbar punch and steroids. I am now 38 and not had one symptom. This whole time I have been on a progesterone only pill. I would like to come off the pill now but scared to incase the ms comes back. Can anyone recommend what to do ?



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