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Niedrigdosierte transdermale Östradiol-Antiandrogen-Therapie

Primärprävention des Diabetes mellitus Typ II in der Postmenopause

Low-dose transdermal therapy with estradiol and anti-androgen

Primary prevention of diabetes mellitus type 2 in the menopause

  • Arzneimitteltherapie
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

In der Postmenopause (PM) kommt es häufig zu einem negativen Circulus vitiosus aus Gewichtszunahmen, relativer Hyperandrogenämie, Dyslipidämie, Hypertonus, Insulinresistenz und schließlich Diabetes mellitus Typ II (DM) sowie schweren Herz-Kreislauf-Erkrankungen. Bei 474 postmenopausalen Frauen unter niedrig dosierter Hormonersatztherapie (HET) mit bioidentischen Hormonen sowie 1073 prämenopausalen unbehandelten Frauen wurde ein oraler Glukosetoleranztest mit Bestimmung von Insulin und Glukose in 5 verschiedenen Gewichtsgruppen durchgeführt. Zusätzlich wurden weitere Parameter des Stoffwechsels bzw. der klinischen Chemie überprüft. Eine solche HET kann den negativen Circulus vitiosus unterbrechen: Der postmenopausale Glukoseanstieg wird durch eine verbesserte Insulinsensitivität kompensiert, die Östrogenwerte in der PM liegen im Bereich der frühen Follikelphase, während die Konzentrationen von Dehydroepiandrosteronsulfat und Androstendion deutlich abfallen. Die kontrollierte, niedrig dosierte HET mit bioidentischem Östradiol in Kombination mit einem niedrig dosierten Antiandrogen verhindert die Entwicklung schwerer Volkskrankheiten wie Insulinresistenz und Diabetes mellitus und ist als eine wesentliche primärpräventive Maßnahme in der Postmenopause anzusehen, die allen postmenopausalen Frauen zur Verfügung stehen sollte.

Abstract

The vicious circle of increased body weight (BW), relative hyperandrogenemia (HA), dyslipidemia (DL), hypertension (H), insulin resistance (IR) and ultimately type 2 diabetes mellitus (DM) and severe cardiovascular disease (CVD) often affects postmenopausal women (PM). A total of 474 postmenopausal women on low-dose hormone replacement therapy (HRT) were compared to 1,073 premenopausal women receiving no therapy. An oral glucose tolerance test (OGTT) with measurement of insulin (I) and glucose (G) was carried out in women in five different body weight groups. Additionally, parameters of metabolism and other clinical chemistry measurements were carried out. Low-dose HRT can effectively halt this vicious circle. The increase in glucose levels in postmenopausal women is compensated by better insulin sensitivity. The production of insulin was not increased in comparison with premenopausal women and free insulin-like growth factor 1 (IGF-1) was even shown to decrease. The estrogen and androgen values in PM are comparable to that of premenopausal women in the early follicular phase. Controlled, low-dose HRT with bioidentical natural estrogen in combination with low dose antiandrogen can prevent the development of severe common diseases, such as IR and DM and is therefore an important method of primary prevention in postmenopausal women which should be made readily available.

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Abb. 1

Abbreviations

Δ4A:

Androstendion

A1, A2, A3:

Adipositas unterschiedlichen Ausmaßes

ADA:

„American Diabetes Association“

ADMA:

Asymetrisches Dimethylarginin (Vasodilatator)

AUC:

„Area under the curve“

BMI:

Body-Mass-Index

CPA:

Cyproteronazetat (Antiandrogen)

CRP:

C-reaktives Protein

DHEA:

Dehydroepiandrosteron

DHEAS:

Dehydroepiandrosteronsulfat

DHT:

Dihydrotestosteron

DM:

Diabetes mellitus Typ II

E1:

Östron

E2:

Östradiol

F:

Kortisol

FIBR:

Fibrinogen

fT:

Freies Testosteron

fT3:

Freies Trijodthyronin

fT4:

Freies Thyroxin

G0 :

Nüchternglukosekonzentration

G60 :

Glukosekonzentration nach 60 min im oGTT

G120 :

Glukosekonzentration nach 120 min im oGTT

GC:

Gesamtcholesterin

GLUT4:

Glukosetransporter 4

HA:

Hyperandrogenämie

HbA1c :

Glykohämoglobin

HDL:

High-Density-Lipoprotein

HET:

Hormonersatztherapie

HKE :

Herz-Kreislauf-Erkrankung

HOM:

Homocystein

HOMA:

„Homeostasis model assessment“

HS:

Harnsäure

I0 :

Nüchterninsulinwert

I60 :

Insulinkonzentration nach 60 min im oGTT

I120 :

Insulinkonzentration nach 120 min im oGTT

IGF:

„Insulin-like growth factor“

IGFBP3:

„Insulin-like growth factor binding protein 3“

IL:

Interleukin

IR:

Insulinresistenz

IS:

Insulinsensitivität

KG:

Körpergewicht

LDL:

Low-Density-Lipoprotein

Lp(a):

Lipoprotein (a)

NFκB:

Nukleärer Faktor kappa B

NPL:

Neoplasma

n.s.:

Nicht signifikant

oGTT:

Oraler Glukosetoleranztest

PAI-1:

Plasminogenaktivatorinhibitor

PCO:

Polyzystische Ovarien

pIR:

Primäre Insulinresistenz

SHBG:

Sexualhormon bindendes Globulin

sIR:

Sekundäre Insulinresistenz

T:

Testosteron

TG:

Triglyzeride

TNF-α:

Tumornekrosefaktor α

TSH:

Thyroidea stimulierendes Hormon

WHO:

Weltgesundheitsorganisation

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Authors and Affiliations

  1. Institut für Präventive Medizin, Uhlandstraße 19, 10623, Berlin, Deutschland

    L. Moltz

  2. Abteilung für Epidemiologie, Medizinische Fakultät, Universität Ulm, Ulm, Deutschland

    R.W. Holl

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Correspondence to L. Moltz.

Anhang

Anhang

Kürzel (s. Tab. 3, Tab. 4, Tab. 5 und Tab. 6) und Normalbereiche der Analytik sind für metabolische Parameter und für Hormone in Tab. 8 aufgeführt.

Tab. 8 Normalbereiche der Analytik
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Moltz, L., Holl, R. Niedrigdosierte transdermale Östradiol-Antiandrogen-Therapie. Gynäkologische Endokrinologie 10, 281–288 (2012). https://doi.org/10.1007/s10304-012-0510-x

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