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 Hormonersatztherapie, hormonelle Kontrazeption und IVF: Empfehlungen zur Hormongabe bei Betroffenen mit erblicher Tumorprädisposition  
 Introduction: In the context of genetic counseling for women with familial increased cancer risk patients often ask about possible hormonal therapies or additional hormone administration with HRT, contraception and IVF. Since there is insufficient or conflicting information on the therapeutic recommendations for these patients, a detailed search of the

scientific literature is to be carried out in the course of this work. Based on this, recommendations for HRT, contraception, and IVF should be summarized.

Material and methods: The question was answered by means of systematic literature research (PubMed).

Target: Menopause describes the transition from the reproductive phase to the extinction of a woman's ovarian function. The hormonal transition is characterised by a physiological drop in oestrogen and progesterone levels, which leads to typical menopausal symptoms such as sweating, insomnia and depressive moods in the majority of women. To treat the symptoms, hormone replacement therapy (HRT) is possible. One possible side effect is an increased risk of endometrial cancer, breast cancer and ovarian cancer. This is particularly relevant for women with a family history of cancer, especially those with pathogenic variants in BRCA1

and BRCA2. Due to the genetic preload, some of the mutation carriers undertake a risk reducing salpingo-oophorectomy (RRSO) premenopausal to counteract the increased risk of

cancer. As a result, it becomes necessary for these patients to treat surgically entered menopause with HRT. The question arises of the correct choice of therapy, taking into account the genetic risks, the pre-existing diseases and the age of those affected.

Furthermore, the question arises to what extent hormonal contraception or IVF (in vitro fertilization) or assisted reproduction (due to hormone administration) influence the tumor risk in known tumor predisposition syndromes.

Therefore, the recommended therapeutic options regarding hormonal treatments (HRT, hormonal contraception, IVF) in women with tumor predisposition syndromes will be discussed in the context of this work.

Results: BRCA1/2 mutation carriers are advised to undergo RRSO between the ages of 35 and 40 (BRCA1) or 40 and 45 (BRCA2) after family planning has been completed. This

reduces the incidence of ovarian cancer by up to 96%. (1, 2) Short-term use of HRT for 3 to 5 years after RRSO does not increase the risk of BRCA1 mutation carriers.(2) A similar risk profile is assumed for BRCA2 mutation carriers. (3, 4) With regard to ovarian cancer risk, no increased risk from HRT was observed for BRCA1 mutation carriers. There was no

significant risk increase from estrogens use or risk reduction from progestogens. (5) The ESHRE Guidelines recommend short-term use of 17-beta estradiol or conjugated estrogens in combination with oral cyclic progesterone with intact uterus for BRCA mutation carriers.(6)

The use of oral contraception in BRCA mutation carriers appears to reduce the risk of ovarian cancer, with the protective effect increasing with long-term use and maintaining even 20 years after discontinuation of the OC. (7, 8) The maximum risk reduction was demonstrated when taking the OC for at least 5 years (BRCA1) and at least 3 years (BRCA2). (9) Combined OC reduces ovarian cancer risk. (10) Breast cancer risk in BRCA mutation carrier is significantly increased using OC, especially when starting combined OC before age 20. (8, 11) For patients with Lynch syndrome, there was no reduction in endometrial cancer risk

from OC use in a study published in 2024. A reduction in risk from long-term use of OC does not appear until age 45. (12)

Different types of fertility treatment do not result in an increased risk of breast cancer in BRCA1 and BRCA2 mutation carriers. (13, 14) A potential increased risk of ovarian cancer in BRCA mutation carriers has also not been demonstrated in this context. (15, 16) Based on the current state of research, a general exclusion of these patients from fertility treatments is not necessary. (17) In general, fertility treatment for BRCA mutation carriers is not

contraindicated, provided there is sufficient observation.(14)

For moderate and low-risk genes such as CHEK2, BRIP1, PALB2, ATM, CDH1, RAD51C/D, STK11, PTEN and Li-Fraumeni syndrome, little or no data on the safety of the use of hormonal therapies in mutation carriers can be demonstrated so far.

Conclusion: The data on hormonal therapy options for mutation carriers is mainly limited by the lack of long-term data. As diagnostic options progress, it is increasingly possible to

detect mutations that should be considered for HRT, OC or IVF. To date, except for BRCA mutations, no uniform therapeutic recommendations can be made for the use of HRT, OC and fertility treatments. Therefore, it will be necessary to conduct specific studies for those populations at risk and to collect long-term data on the safety of their use.  
   
 
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Autorinnen*Autoren / Co-Autorinnen*Co-Autoren
  Aschbacher, Sophie
Betreuende Einrichtung / Studium
  Diagnostik & Forschungsinstitut für Humangenetik
 UO 202 Humanmedizin  
Betreuung / Beurteilung
  Geigl, Jochen Bernd; Assoz. Prof. Priv.-Doz. Dr.med.
  Schreiner, Elisabeth; Dr.med.univ.