Menstrual irregularities and TSC

To date there has been little research on the impact of TSC on the reproductive system and menstrual cycles.  Researchers have found that women with TSC self-reported significant menstrual cycle irregularities, elevated rates of miscarriage and medical histories that suggest other reproductive disorders.  The use of mTOR inhibitors (mTORi), such as everolimus, to control symptoms of TSC makes understanding the impact of TSC on the female reproductive system even more difficult. 

In combined data from two mTORi (everolimus) trials – EXIST 1 and 2 – 38.4% of female participants with TSC experienced at least one episode of menstrual irregularity while taking mTORi, compared to 2.3% in the placebo group.  There are currently no studies that provide insight on the effect of mTORi on the onset of menstruation (menarche). 

About this study

This study aimed to contribute to the knowledge of female reproductive dysfunction in TSC and to explore how mTORi affect the menstrual cycle.  This study used self-reported data in women living with TSC, comparing it to data obtained from their mothers. 

How the study was conducted

The researchers designed a web-based survey for females with TSC aged 8 years or older. Parents/caregivers of those who were 8-17 years of age or with cognitive impairment were required to fill out the survey.  100 females with TSC between the ages of 9-58 years were recruited. 

43% of responses were from parents/caregivers and 57% of respondents answered their own questions.  Data was collected over a 6-month period between June and December 2019.  Participants were asked about menstrual irregularities (longer or shorter cycles than normal, heavy bleeding, delayed puberty), menarche/menopause and oral contraceptive/reproductive history.

Outcomes of the study

Even though the mTOR pathway is key in regulating the onset of puberty, there is no evidence of this being abnormal among females with TSC.  This study reported an average age of menarche of 12.3 years in females with TSC, which is not significantly different to the general population, and in line with previous studies.  When compared to their unaffected mothers, the age of menarche in women with TSC is slightly earlier (12.3 years vs 13 years).  In the general population, the opposite trend occurs.  The study found no statistical significance in age of menarche in females with TSC who take mTORi.

After puberty and in line with other studies, the study found that women with TSC present with manifestations of abnormal ovarian function, evidenced by increased rates of menstrual irregularities, miscarriages and infertility.  The authors compared women with TSC taking mTORi with women with TSC not taking mTORi and found a higher rate of menstrual irregularities in the group taking mTORi  – 74% vs 48% in the non mTORi group.  Women living with TSC in both the mTORi and non-mTORi groups had higher rates of menstrual irregularities than the general population. 

The average age of menopause in eligible respondents was 51 years of age, compared with an average age of 47.5 years in their mothers, which is comparable to the general population.  The authors note that this is different to previous studies which have found women with TSC present with early menopause.

Limitations of the study

This is small study size and uses survey data which relies on participant’s recall.  The authors acknowledge that respondents may not have reported data on menarche and menopause correctly due to inaccuracy in recalling the timing of these events.  Additionally, participants were not required to answer questions about seizure medications, gynaecological surgeries or uterine fibroids. All of these factors can influence menstrual irregularity and menopause. 

Implications of the study

This study has added to the understanding of menstrual irregularities that present in women living with TSC and identified a previously unreported feature of TSC – a tendency towards early menarche.  Further studies with larger cohorts are needed to pave the way for treatment options to improve the reproductive health of women living with TSC. 

Mowrey, K., Northrup, H., Hashmi, S. S., & Rodriguez-Buritica, D. (2022). Expanding Our Knowledge of Menstrual Irregularities Reported by Females With Tuberous Sclerosis Complex. Frontiers in Reproductive Health, 4, 798983.

Full article available at:

To find out more about TSC and how it may affect a woman’s menstrual cycle, please join our Zoom Education Event taking place on Wednesday 26 July 2023, 7.30pm AEST. This event is FREE for TSA members. You can register now at:


This information is intended to provide some insights into recent TSC-related research.  It is not intended to, and it should not, constitute medical or other advice.  Readers are warned not to take any action without first seeking medical advice.