Research Article|Articles in Press

Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome Individuals

Published:March 16, 2023DOI:


      Study Objectives

      Incidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterize factors associated with AUB among TS individuals. A secondary objective was to evaluate the management of AUB among this patient population.

      Design, setting, participants, and intervention

      We conducted a retrospective chart review to evaluate TS individuals undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen (TDE). A total of 45 participants were identified between January 2007 and June 2019.


      Of the 45 TS individuals included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs. 28%) and a duration of unopposed estrogen greater than 18 months (63% vs. 41%), undergo progestin cycling less often than monthly (69% vs. 0%), use a micronized progestin dose of less than 200 mg (25% vs. 14%), and be noncompliant with HRT (19% vs. 0%) compared to those who did not experience AUB.


      There is a relatively high incidence of AUB among TS individuals undergoing pubertal induction with TDE. Care providers should consider the clinical factors examined to guide monitoring and management of TS individuals on HRT.


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        • Gravolt C
        • Andersen N
        • Conway G
        • Dekkers O
        • Geffner M
        • Klein K
        • et al.
        Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting.
        Eur J Endocrinol. 2017; 177: G1-70
        • Dabrowski E
        • Jensen R
        • Johnson EK
        • Habiby RL
        • Brickman WJ
        • Finlayson C.
        Turner Syndrome Systematic Review: Spontaneous Thelarche and Menarche Stratified by Karyotype.
        Horm Res Paediatr. 2019; 92: 143-149
        • Pasquino AM
        • Passeri F
        • Pucarelli I
        • Segni M
        • Municchi G.
        Spontaneous pubertal development in Turner's syndrome. Italian Study Group for Turner's Syndrome.
        J Clin Endocrinol Metab. 1997; 82: 1810-1813
        • Tanaka T
        • Igarashi Y
        • Ozono K
        • Ohyama K
        • Ogawa M
        • Osada H
        • Onigata K
        • Kanzaki S
        • Kohno H
        • Seino Y
        • et al.
        Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.
        Clinical Pediatric Endocrinology. 2015; 24: 167-173
        • Negreiros LP
        • Bolina ER
        • Guimaraes MM.
        Pubertal development profile in patients with Turner syndrome.
        Journal of Pediatric Endocrinology and Metabolism. 2014; 27: 845-849
        • Munro MG
        • Critchley HO
        • Broder MS
        • Fraser IS.
        FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. FIGO Working Group on Menstrual Disorders.
        Int J Gynaecol Obstet. 2011; 113: 3-13
        • Hernandez
        • Dietrich
        Abnormal uterine bleeding in the adolescent. American College of Obstetricians and Gynecologists.
        Obstet Gynecol. 2020; 135: 615-621
        • American College of Obstetrics and Gynecology
        Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women. ACOG Practice Bulletin No. 128.
        Obstet Gynecol. 2012; 120: 197-206
        • TorresSantiago L
        • Mericq V
        • Taboada M
        • Unanue N
        • Klein K
        • Singh R
        • Hossain J
        • Santen R
        • Ross J
        • Mauras N.
        Metabolic effects of Oral vs. Transdermal 17beta Estradiol (E2): a randomized clinical trial in girls with Turner Syndrome.
        Journal of Clinical Endocrinology and Metabolism. 2013; 98
        • Fraser IS
        • Critchley HO
        • Munro MG
        • Broder M.
        Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding?.
        Hum Reprod. 2007; 22: 635-643
      1. Approach to common side effects.
        in: Wallach M Grimes DA Chaney EJ Modern oral contraception: updates from The Contraception Report. Emron, Totowa, N.J.2000: 70-76
        • Hickey M.
        • Doherty D.A.
        • Fraser I.S.
        • Sloboda D.M.
        • Salamonsen L.A.
        Why does menopausal hormone therapy lead to irregular uterine bleeding? Changes to endometrial blood vessels.
        Human Reproduction. 2008; 23: 912-918
        • Archer DF
        • Jensen JT
        • Johnson JV
        • Borisute H
        • Grubb GS
        • Constantine GD.
        Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results.
        Contraception. 2006 Dec; 74: 439-445
      2. Seasonique [package insert]. Duramed Pharmaceuticals, 2006.

        • Figtree GA
        • Noonan JE
        • Bhindi R
        • Collins P
        Estrogen receptor polymorphisms: significance to human physiology, disease and therapy.
        Recent Pat DNA Gene Seq. 2009; 3: 164-171
        • American College of Obstetricians and Gynecologists
        Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Committee Opinion No. 557.
        Obstet Gynecol. 2013; 121: 891-896
        • DeVore GR
        • Owens O
        • Kase N.
        Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding- a double blind randomized control study.
        Obstet Gynecol. 1982; 59: 285-291
        • Munro MG
        • Mainor N
        • Basu R
        • Brisinger M
        • Barreda L.
        Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial.
        Obstet Gynecol. 2006; 108: 924-929
        • James AH
        • Kouides PA
        • Abdul-Kadir R
        • Dietrich JE
        • Edlund M
        • Federici AB
        • et al.
        Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel.
        Eur J Obstet Gynecol Reprod Biol. 2011; 158: 124-134
        • National Collaborating Centre for Women's and Children's Health
        National Institute of Clinical Excellence. Heavy menstrual bleeding, Clinical guideline.
        RCOG Press, London2007
        • Franchini M
        • Marano G
        • Mengoli C
        • et al.
        Red blood cell transfusion policy: a critical literature review.
        Blood Transfus. 2017; 15: 307-317
        • Klein Karen O
        • Rosenfield Robert L
        • Santen Richard J
        • Gawlik Aneta M
        • Backeljauw Philippe F
        • Gravholt Claus H
        • Sas Theo C J
        • Mauras Nelly
        Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations.
        The Journal of Clinical Endocrinology & Metabolism. May 2018; 103: 1790-1803
        • Short MW
        • Domagalski JE.
        Iron deficiency anemia: evaluation and management.
        Am Fam Physician. 2013 Jan 15; 87: 98-104
        • De Franceschi L
        • Iolascon A
        • Taher A
        • Cappellini MD.
        Clinical management of iron deficiency anemia in adults: Systemic review on advances in diagnosis and treatment.
        Eur J Intern Med. 2017; 42: 16-23