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Summary

Langton et al. [1] have examined the association of oral contraceptive (OC) use and tubal ligation (TL) with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. A total of 106,633 NHSII participants were included who were premenopausal (aged 25-42) at the initiation of the study. The use, duration and type of OC and TL were recorded at the beginning of the study and every 2 years. Menopausal status and age were evaluated every 2 years. Follow-up continued until early menopause, age 45, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up occurred. Authors used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals adjusted for lifestyle, dietary, and reproductive factors. Over 1.6 million person-years, 2,579 participants of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with the risk of early menopause. Compared to women who never used OCs, those reporting 120+ months of OC use did not have a significant risk for early menopause (HR 1.01 95% CI: 0.87-1.17; p for trend=0.71). Contrary to this, TL was associated with a modest increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28).

Commentary

Premature ovarian insufficiency (POI) and early menopause, defined as loss of ovarian activity prior to 40 years of age or menopause between the ages of 40 and 45 years, respectively, are associated with significant adverse health impacts [2]. Recent data indicate that the prevalence of POI and early menopause is greater than was previously thought, affecting more than 10% of women [2,3]. Bio- psycho and social risk factors have been associated with POI/early menopause or earlier age at menopause including genetic, autoimmune, reproductive, lifestyle, early-life, social/environmental, and iatrogenic aspects [4,5]. Despite this, establishing a causal role and the underlying mechanisms remains elusive [6]. Bilateral tubal ligation (BTL) is an effective and safe method for family planning; however, the blood supply of the ovaries may be affected during the procedure [7]. Bilateral tubal ligation may reduce the ovarian blood flow, thus leading to the decrease of the total follicular pool, ovarian function and an early state of hormonal deficiency [7]. Several publications suggest that BTL induce alterations of the endocrine profile of operated women. Based on the review of the literature, no conclusive statements can be made in this regard due to contradictory results between publications [7]. Ainsworth et al [8], have shown that BTL did not affect age at natural menopause in the three large cohorts. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. This study collected the e following variables: race, age at menarche and menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception [8]. The type of TL and age at TL were manually abstracted in cohort 1. For cohorts 2 and 3, history of TL was obtained from an institutional form, completed by patient report. [8]. The authors concluded that when TL is correctly performed it should not compromise ovarian function. If BTL interferes with the vascular supply of the ovaries, it may not be significant enough to cause an earlier onset of menopause [8]. Other authors have concluded the same when the procedure is correctly performed [9]. Larger randomized case-control studies should be performed to enable to make stronger conclusions about the long-term effect of TL as a method for birth control over early menopause [9]. The study by Langton et al, is to date the largest to examine the association of OC use and BTL with early natural menopause [1]. Although BTL was associated with a moderately increased risk of early menopause, their findings do not support any risk of the use of OCs.

Mónica L. Ñañez, MD, PhD
National University of Cordoba, Cordoba, Argentina
President of Argentine Association of Menopause and Andropause

References

  1. Langton CR, Whitcomb BW, Purdue-Smithe AC, et al. Association of oral contraceptives and tubal ligation with risk of early natural menopause. Hum Reprod. 2021;36(7):1989-1998.
    https://pubmed.ncbi.nlm.nih.gov/33822044/
  2. Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019;22(4):403-411.
    https://pubmed.ncbi.nlm.nih.gov/30829083/
  3. Yang Y, Huang W, Yuan L. Effects of Environment and Lifestyle Factors on Premature Ovarian Failure. Adv Exp Med Biol. 2021;1300:63-111.
    https://pubmed.ncbi.nlm.nih.gov/33523430/
  4. Mishra GD, Chung HF, Cano A, et al. EMAS position statement: Predictors of premature and early natural menopause. Maturitas. 2019;123:82-88.
    https://pubmed.ncbi.nlm.nih.gov/31027683/
  5. Arinkan SA, Gunacti M. Factors influencing age at natural menopause. J Obstet Gynaecol Res. 2021;47(3):913-920.
    https://pubmed.ncbi.nlm.nih.gov/33350022/
  6. Ñañez M. Falla ovárica prematura. Tratado de Reproducción Humana: fisiopatología, fertilización asistida, reprogenética y aplicaciones clínicas/Sociedad Argentina de Medicina Reproductiva. 1era Edición. Ciudad Autónoma de Buenos Aires. Ascune 2020. 555/569. ISBN 978-950-9124-85-1.
  7. Tayeh GA, Nabaa T, Habib O, et al. Tubal ligation and early menopause: a case-control study. Obstet Gynecol Int J. 2018;9(2):114-116.
    https://medcraveonline.com/OGIJ/tubal-ligation-and-early-menopause-a-case-control-study.html
  8. Ainsworth AJ, Baumgarten SC, Bakkum-Gamez JN, Vachon CM, Weaver AL, Laughlin-Tommaso SK. Tubal Ligation and Age at Natural Menopause. Obstet Gynecol. 2019;133(6):1247-1254.
    https://pubmed.ncbi.nlm.nih.gov/31135741/
  9. İbik Y, Durukan H, Yazıcı G. The effect of bilateral tubal ligation on menopause age and symptoms. J Surg Med. 2021;5(5):404-407.
    https://doi.org/10.28982/josam.89987

 


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