Pregnancy and hormonal contraceptives in vestibular schwannoma

Pregnancy and hormonal contraceptives in vestibular schwannoma

Vestibular schwannoma, pregnancy and hormonal contraceptives

Vestibular schwannoma, also known as acoustic neuroma, is a benign tumour that arises from the vestibular portion of the eighth cranial nerve. While the exact cause of vestibular schwannomas is not fully understood, there has been some research suggesting a potential link between pregnancy and the growth of these tumours. There is no evidence that pregnancy per se causes the development of vestibular schwannomas.

It is unclear to what extent estrogen stimulates growth in these tumours, as some tumours may lack estrogen receptors, or our detection methods may not be sensitive enough. Progesterone, another hormone that increases during pregnancy, has also been investigated with uncertain results.

Pregnant women with VS are at a significantly increased risk of abortion and death compared to their non-pregnant counterparts (1).

The growth pattern and size of vestibular schwannoma during pregnancy

While vestibular schwannomas (VS) are usually slow-growing tumours, they can experience rapid growth during pregnancy due to elevated estrogen levels and increased hemodynamics. This accelerated growth can cause tumours to grow in size by at least 4 mm per year, leading to more severe symptoms and potentially even acute obstructive hydrocephalus, especially in the third trimester (2,3,4). Research indicates that pregnant individuals with VS often have larger tumours compared to non-pregnant individuals, with previous cases showing tumours exceeding 4 cm in size (5,6).

The effect of estrogen and progesterone on vestibular schwannoma

Pregnancy is a period of significant hormonal changes in a woman’s body, with elevated levels of estrogen and progesterone playing critical roles in maintaining the pregnancy. These hormones have been found to impact the growth and development of certain types of tumours, including vestibular schwannomas.

Estrogen, in particular, may have stimulatory effects on the growth of vestibular schwannomas. This is because estrogen receptors are present in the Schwann cells that make up the tumour, and when estrogen binds to these receptors, it can enhance cell proliferation and tumour growth (7,9).

Progesterone is another important hormone that may play a role in vestibular schwannomas, as it has been shown to have both stimulatory and inhibitory effects on tumour growth. In some studies, progesterone has been found to promote the growth of vestibular schwannomas by increasing cell proliferation and inhibiting cell death. However, in other studies, progesterone has been shown to inhibit tumour growth by reducing cell proliferation and inducing cell death.

Hormonal receptors in vestibular schwannona

Management of vestibular schwannoma during pregnancy

Vestibular schwannoma during pregnancy presents a dilemma in management. Although rare, these tumours tend to be larger and grow faster in pregnant women than men and non-pregnant women. Long before the availability of MRI, neurosurgeon Harvey Cushing noted in 1917 that vestibular schwannomas grow more quickly in pregnant women (8).

Managing a large, rapidly growing vestibular schwannoma during pregnancy can be challenging. Obstetricians are advised to be cautious when diagnosing pregnant women with symptoms such as headache, vomiting, and hearing loss, as they may be signs of an underlying medical condition such as vestibular schwannoma that need immediate attention (10,11).

Fortunately, MRI is considered safe for evaluating suspected tumours during pregnancy. However, the risks to both the mother and baby must be carefully considered, with the safest time for surgery likely being the second trimester. Management decisions should involve thorough consultation and discussion among the mother, obstetrician, neurotologist, neurosurgeon, and other involved parties.

Hormonal contraception and vestibular schwannoma

The use of hormonal contraception has also been implicated in the growth of vestibular schwannomas. There is no evidence that hormonal contraception causes the development of vestibular schwannomas.

Oral contraceptives contain synthetic forms of estrogen and progesterone, which can influence the hormonal balance in the body. Some studies have suggested that the use of hormonal contraceptives may promote the growth of vestibular schwannomas by providing a continuous source of exogenous hormones that can stimulate tumour cell proliferation (12).

There have been numerous studies that have failed to find a link between contraceptive hormones and vestibular schwannoma growth. While hormonal factors may play a role in the development of some tumours, the evidence supporting a direct correlation between contraceptive hormones and vestibular schwannoma growth is lacking. 

Therefore, it would be inaccurate to conclude that contraceptive hormones cause or stimulate growth in vestibular schwannoma based on the current available evidence. Further research may be needed to investigate any potential relationships between hormonal factors and the development of this type of tumour.

Hortmonal contraceptives and Neurofibromatosis type 2

A study by Evans et al. (2009) investigated the impact of pregnancy and hormonal contraceptives on the growth of vestibular schwannomas in women with NF2. The researchers found that both pregnancy and the use of hormonal contraceptives were associated with an increased risk of tumour growth (13). Interestingly, they also found that women who had been pregnant at an earlier age were more likely to have larger tumours at the time of diagnosis. This suggests that the hormonal changes associated with pregnancy may have a long-term impact on the growth of vestibular schwannomas in neurofibromatosis type 2 (NF2).

Bilateral vestibular schwannoma in NF2

References

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2. Shah KJ, Chamoun RB. Large vestibular schwannomas presenting during pregnancy: management strategies. J Neurol Surg B Skull Base. (2014) 75:214–20. doi: 10.1055/s-0034-1370784

3. Kurowska-Mroczek E, Zabek M, Osuch B, Stelmachów J. Therapeutic management of acoustic neurinoma during twin pregnancy: a case report. J Reprod Med. (2009) 54:393–6.

4. Doyle KJ, Luxford WM. Acoustic neuroma in pregnancy. Am J Otol. 1994 Jan;15(1):111-3. PMID: 8109621.

5. Kasantikul V, Brown WJ. Estrogen receptors in acoustic neurilemmomas. Surg Neurol. 1981 Feb;15(2):105-9. doi: 10.1016/0090-3019(81)90023-9. PMID: 7245001.

6. Gaughan RK, Harner SG. Acoustic neuroma and pregnancy. Am J Otol. 1993 Jan;14(1):88-91. PMID: 8424484.

7. Brown CM, Ahmad ZK, Ryan AF, Doherty JK. Estrogen receptor expression in sporadic vestibular schwannomas. Otol Neurotol. 2011 Jan;32(1):158-62. doi: 10.1097/MAO.0b013e3181feb92a. PMID: 21099731; PMCID: PMC3073320.

8. Cushing, H. Tumors of the Nervus Acusticus and the Syndrome of the Cerebellopontine Angle. Philadelphia: W.B. Saunders, Co; 1917. p. 148

9. Patel AK, Alexander TH, Andalibi A, Ryan AF, Doherty JK. Vestibular schwannoma quantitative polymerase chain reaction expression of estrogen and progesterone receptors. Laryngoscope. 2008 Aug;118(8):1458-63. doi: 10.1097/MLG.0b013e318177e20b. PMID: 18670322; PMCID: PMC3570025.

10. Kachhara R, Chandrika Devi CG, Nair S, Bhattacharya RN, Radhakrishnan VV. Acoustic neurinomas during pregnancy: report of two cases and review of literature. Acta Neurochir. (2001) 143:587–91. doi: 10.1007/s007010170063

11. Bao M, He Y, Tao Y, Liu L, Li Y, Zhu Y, Huang Q, Zhang M, Wu B, Wang H. Large vestibular schwannomas presenting in the late state of pregnancy: a case report and literature review. Front Neurol. 2023 Dec 1;14:1270989. doi: 10.3389/fneur.2023.1270989. PMID: 38107637; PMCID: PMC10722247.

12. Benson VS, Pirie K, Green J, Bull D, Casabonne D, Reeves GK, Beral V; Million Women Study Collaborators. Hormone replacement therapy and incidence of central nervous system tumours in the Million Women Study. Int J Cancer. 2010 Oct 1;127(7):1692-8. doi: 10.1002/ijc.25184. PMID: 20091865.

13. Jaiswal S, Agrawal V, Jaiswal AK, Pandey R, Mahapatra AK. Expression of estrogen and progesterone receptors in vestibular schwannomas and their clinical significance. J Negat Results Biomed. 2009 Nov 4;8:9. doi: 10.1186/1477-5751-8-9. PMID: 19889208; PMCID: PMC2777842.

14. Evans, D.R. Neurofibromatosis type 2 (NF2): A clinical and molecular review. Orphanet J Rare Dis 4, 16 (2009). https://doi.org/10.1186/1750-1172-4-16