PMID- 33369022
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20210802
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Linking)
VI  - 68
IP  - 3
DP  - 2021 Mar
TI  - Menstrual disorders associated with sirolimus treatment.
PG  - e28867
LID - 10.1002/pbc.28867 [doi]
AB  - INTRODUCTION: Sirolimus has become a pillar in the treatment of vascular 
      anomalies due to its inhibition of the mammalian target of rapamycin (mTOR). 
      Adverse effects include metabolic and hematologic disorders among others, 
      although menstrual disorders have not been well described. MATERIALS AND METHODS: 
      Retrospective review of patients with vascular anomalies on sirolimus treatment 
      was performed. Patients presenting menstrual alterations were included. MAIN 
      RESULTS: One hundred and thirty-six patients with vascular anomalies on treatment 
      with sirolimus were reviewed, finding seven women out of 74 (9.4%) who presented 
      menstrual alterations attributable to the treatment. These seven patients 
      presented with different vascular malformations and three showed pathogenic 
      variants in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit 
      alpha (PIK3CA) in affected tissue. Partial response in six and stability in one 
      patient was obtained after treatment, administered for an average of 27.5 months 
      (6-48). Five patients have completed treatment and two patients continue on after 
      12 and 15 months, respectively. All patients reported regular menstrual cycles 
      prior to sirolimus treatment. One patient presented with amenorrhea for 4 months 
      after treatment initiation that later spontaneously resolved. The other six 
      patients presented with hypermenorrhea, four of them associating metrorrhagia. 
      Most patients presented with mild menstrual alterations, without needing dose 
      reduction or withdrawal, although one discontinued sirolimus due to 
      hypermenorrhea, metrorrhagia, and hematuria. After sirolimus withdrawal, regular 
      menstrual cycles were restored in five patients. CONCLUSION: Sirolimus treatment 
      can produce menstrual disorders as adverse effects. Although mild and reversible 
      upon dose reduction or cessation of treatment, patients and physicians should be 
      aware on this potential side effect.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Triana, Paloma
AU  - Triana P
AUID- ORCID: 0000-0002-8176-6010
AD  - Vascular Anomalies Unit, Department of Pediatric Surgery, Children's Hospital La 
      Paz, Madrid, Spain.
FAU - Lopez-Gutierrez, Juan Carlos
AU  - Lopez-Gutierrez JC
AD  - Vascular Anomalies Unit, Department of Pediatric Surgery, Children's Hospital La 
      Paz, Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20201227
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Antibiotics, Antineoplastic)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibiotics, Antineoplastic/*adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Lymphatic Abnormalities/*drug therapy/pathology
MH  - Menstruation Disturbances/chemically induced/*pathology
MH  - Prognosis
MH  - Retrospective Studies
MH  - Sirolimus/*adverse effects
MH  - Vascular Malformations/*drug therapy/pathology
OTO - NOTNLM
OT  - amenorrhea
OT  - menstrual disorders
OT  - metrorrhagia
OT  - rapamycin
OT  - sirolimus
OT  - vascular anomalies
EDAT- 2020/12/29 06:00
MHDA- 2021/08/03 06:00
CRDT- 2020/12/28 12:39
PHST- 2020/06/25 00:00 [received]
PHST- 2020/12/04 00:00 [revised]
PHST- 2020/12/07 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/12/28 12:39 [entrez]
AID - 10.1002/pbc.28867 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2021 Mar;68(3):e28867. doi: 10.1002/pbc.28867. Epub 2020 
      Dec 27.