The majority of individuals with Turner syndrome (TS) are affected by primary ovarian failure (POI), thus requiring hormonal therapy to induce puberty. However, around 16% of individuals with TS show complete spontaneous pubertal development with menarche (first menstrual cycle).
A study of French TS patients showed that the age of spontaneous menarche was around 13.2 years old. Of these patients, those who had complete spontaneous puberty showed spontaneous breast development at around 11.8 years of age, while those who later experienced pubertal arrest, where puberty begins but is not completed, had spontaneous breast development around 13.7 years of age (Van Der Coelen et al., 2024).
Predictors of Spontaneous Puberty
The predictors of spontaneous puberty are associated with greater ovarian function, or a lower risk of POI.
The greatest predictor of spontaneous puberty is karyotype:
- Individuals with monosomy have the highest risk of gonadal dysgenesis and POI
- Those with mosaicism including XX have approximately a 50% chance of spontaneous puberty (Baggesgaard et al., 2025).
Mosaicism means not all the cells in an individual’s body have the same karyotype. In this case, the mosaicism best associated with spontaneous puberty is having some cells with two X chromosomes, alongside the cells with one X chromosome typical to individuals with TS.
Hormonal Indicators
In childhood, anti-Müllerian hormone (AMH) and Inhibin B can be indicators of ovarian function.
AMH is produced by granulosa cells from small ovarian antral follicles, which contain immature eggs. AMH is the best marker for ovarian activity in mid-childhood, and prepuberal levels above 3pmol/L are suggested to predict spontaneous puberty onset (Baggesgaard et al., 2025).
Inhibin B is also produced by granulosa cells from small ovarian antral follicles, and plays an important role in regulating follicle stimulating hormone (FSH) which will be discussed later (Sims et al., 2012). Low levels of Inhibin B may indicate POI and thus a lower chance of spontaneous puberty. However, researchers urge caution with this interpretation because it may also be a normal finding in healthy girls and adolescents (Baggesgaard et al., 2025).
Around the time of puberty, FSH, luteinizing hormone (LH), and estrogen (estradiol) may also indicate ovarian function. FSH works alongside LH to trigger the production of estrogen in ovaries around puberty, leading to breast development and menarche (Professional, 2025). Low levels of these two hormones can indicate POI. As a result, low levels of estrogen can also indicate POI, though this is a finding sometimes in prepubertal girls without TS (Baggesgaard et al., 2025).
Ultrasound can support the above indicators by analyzing uterine and ovarian volume, as well as the number of antral follicles (Baggesgaard et al., 2025).
Overall, a single biomarker is not sufficient to predict spontaneous pubertal onset, but combinations of the above, interpreted by a healthcare professional, may give some indication of the likelihood (Baggesgaard et al., 2025).
Important Notes about Spontaneous Puberty
Treatment with growth hormone does not appear to have any correlation with the age or likelihood of spontaneous puberty and should be taken as recommended by healthcare professionals (Pasquino et al., 1997).
For those individuals with TS who do experience spontaneous puberty and are able to get pregnant, it is advised that they consult healthcare professionals about the risks and options if they wish to do so. In the French study discussed above, three unassisted pregnancies were observed in the patients with spontaneous puberty, out of which 2 resulted in chromosomal abnormalities and malformations, though this is not a concrete correlation (Pasquino et al., 1997).
Puberty Induction with Hormone Replacement Therapy
The current standard for puberty induction in TS involves hormone replacement therapy (HRT), aiming to mimic the progression of puberty and secondary sex characteristic development (Baggesgaard et al., 2025).
Treatment begins with low doses of estradiol, increased over 2-3 years, and progesterone is added once breakthrough bleeding occurs to induce controlled withdrawal bleeding and establish a menstrual cycle. It is recommended that patients receive coordinated care from pediatric endocrinology, adult endocrinology, and/or gynecology to provide continuity, discuss contraception, and consider future fertility options (Baggesgaard et al., 2025).
The timing of HRT is based on several factors. Typically, evaluation for ovarian failure in TS begins at 9-10 years of age, with treatment typically beginning at 12-13 years of age once ovarian failure has been verified by biochemical testing (FSH and LH in menopausal levels). Measurement of AMH and Inhibin B are adjuncts to assess ovarian reserve.
The psychological readiness of the patient is essential to this decision and HRT may be delayed for the best individual care (Baggesgaard et al., 2025). HRT should only begin once the conclusion of POI can be carefully considered using many factors, including evaluation of pubertal development, hormone levels, uterine volume, and ovarian ultrasound (Pasquino et al., 1997).
Fertility Preservation
Fertility preservation is an important consideration for individuals with TS and their families. Its success is highly correlated with ovarian function, and thus must be considered early in the treatment of individuals with TS.
Vitrification of Oocytes
Vitrification of oocytes (freezing eggs) is the main, FDA-approved method of fertility preservation for individuals with TS. It is generally recommended for patients who have enough ovarian reserves, usually those who have a mosaic karyotype and experienced spontaneous puberty and menarche (Van Der Coelen et al., 2024).
It is difficult to obtain enough mature eggs from women with TS due to lower ovarian function. Small studies have tried to determine predictive parameters for the success of the procedure, but larger cohorts are required to obtain certain results. New, promising research is also looking into treatments that may help increase the number of mature eggs in younger patients (Van Der Coelen et al., 2024).
Ovarian Tissue Cryopreservation
Ovarian tissue cryopreservation (OTC) is a new, experimental treatment that has not yet been approved by the FDA and is still in development.
A clinical trial conducted in Denmark provides an example of what this treatment could look like if approved for clinical use.
First, ovarian function is assessed through measurements of hormones including AMH, inhibin B, FSH, LH, and estradiol, as well as pubertal development, need for HRT, and imaging of uterus and ovaries (Balle et al., 2025).
The patients who agreed to treatment had one ovary removed by laparoscopic surgery and cryopreserved. Once patients were ready for pregnancy planning, they discussed their fertility potential with a gynecologist or fertility specialist. If autotransplantation (transplantation of previously removed material from oneself), was the best option, the thawed ovarian tissue was transplanted into the patient’s remaining ovary (Balle et al., 2025)..
Thus far, most of the patients in the cohort have not reached an age at which they may decide to pursue pregnancy, so long-term outcomes are not known. No live birth has yet been reported in women with TS following autotransplanation of cryopreserved ovarian tissue (Balle et al., 2025).
It is also important to consider the potential consequences of removing one ovary, and more long-term research is needed to determine how it may influence the natural progression of puberty and other clinical implications (Balle et al., 2025).
Conclusion
Spontaneous puberty is a possibility for individuals with TS that must be considered when evaluating options for pubertal induction and fertility treatment. It is not easily predictable by one single marker, but a mosaic karyotype with XX is the strongest predictor.
Both current and potential fertility treatments for individuals with TS are favored for individuals who experienced spontaneous puberty, as higher ovarian function improves outcomes.
Ultimately, pubertal induction and fertility treatment for individuals with TS are continually improving, and it is important for patients and their families to consult healthcare professionals in several disciplines, including pediatric endocrinology, adult endocrinology, and gynecology to learn about all the options and recommended paths to take.
References
Baggesgaard, C. M. B., Fischer, M. B., Pedersen, A. T., Main, K. M., & Hagen, C. P. (2025). Predictors of spontaneous puberty – guiding of puberty induction in Turner syndrome. Expert Review of Endocrinology & Metabolism, 21(1), 9–12. https://doi.org/10.1080/17446651.2025.2609597
Balle, C. M., Nørgaard, S. M., Baggesgaard, C. M. B., Valsted, L. B., Viuff, M. H., Naeraa, R. W., Dueholm, M., Jakobsen, M. R., Bache, I., Kristensen, S. G., Fischer, M. B., Hansen, D., Main, K. M., Pedersen, A. T., Hagen, C. P., & Gravholt, C. H. (2025). The Danish Turner Syndrome Cryopreservation study: PROTOCOL for a prospective cohort Study on reproductive outcomes after ovarian tissue cryopreservation in girls with Turner syndrome. Orphanet Journal of Rare Diseases, 20(1), 587. https://doi.org/10.1186/s13023-025-04104-5
Pasquino, A. M., Passeri, F., Pucarelli, I., Segni, M., & Municchi, G. (1997). Spontaneous pubertal development in Turner’s syndrome1. The Journal of Clinical Endocrinology & Metabolism, 82(6), 1810–1813. https://doi.org/10.1210/jcem.82.6.3970
Professional, C. C. M. (2025, November 14). Follicle-Stimulating Hormone (FSH). Cleveland Clinic. https://my.clevelandclinic.org/health/articles/24638-follicle-stimulating-hormone-fsh
Sims, E. K., Addo, O. Y., Gollenberg, A. L., Himes, J. H., Hediger, M. L., & Lee, P. A. (2012). Inhibin B and luteinizing hormone levels in girls aged 6–11 years from NHANES III, 1988–1994. Clinical Endocrinology, 77(4), 555–563. https://doi.org/10.1111/j.1365-2265.2012.04393.x
Van Der Coelen, S., Van Der Velden, J., Nadesapillai, S., Braat, D., Peek, R., & Fleischer, K. (2024). Navigating fertility dilemmas across the lifespan in girls with Turner syndrome—a scoping review. Human Reproduction Update, 30(4), 383–409. https://doi.org/10.1093/humupd/dmae005
Written By Nadia Kim, TSF Volunteer Blog Writer and designed by Adrianna Verzolini
© Turner Syndrome Foundation, 2026
Discover more from Turner Syndrome Foundation
Subscribe to get the latest posts sent to your email.
