THE LANCET – Vol 358 Sep 8, 2001

GABA - Rezeptor

Progesteron GABA

Dia

ze

pa

m

Barbiturate

Pro

ge

ste

ron

-M

eta

bo

l ite

n

GABA

Dia

ze

pa

m

Barbiturate

Pro

ge

ste

ron

-M

eta

bo

l ite

n

Psychopharmaka

unter 30 J.

7%30-39 J.

11%

40-54 J.

24%

55-64 J.

21%

65+ J.

37%

Alterstruktur Männer

(11 Mio. Verordnungen) Alterstruktur Frauen

(24 Mio. Verordnungen)

40-54 J.

21%

55-64 J.

19%

65+ J.

49%

unter 30 J.

3%30-39 J.

8%

Quelle: IMS Health, VIP

58%

42%

68%

32%

bis 54 ab 54 bis 54

ab 54

11% bis zum

40.Lebensjahr

Verordnungsrate

Psychopharmaka

400

300

200

100

0 <35 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 >60

pro 1000 Frauen bzw. Männer Frauen Männer

One-year prevalence of phobia by

age and gender (ECA)

Goldman M., Women and Health, Academic Press 2000

One-year prevalence of panic by

age and gender (ECA)

Goldman M., Women and Health, Academic Press 2000

inhibierender GABA Neurotransmittor hemmt

präpuberträre GnRH-Freisetzung

Endocrine Reviews 22,111(2001)

Endocrine Reviews 22, 135

Cohort differences in the cumulative age of onset

of major depressive episode in females

Schizophrenie beginnt oft in peripubertärem Lebensabschnitt

Neuropharmacology 16,385

Präfontale GABA Neurone subunits bei Schizophrenie verändert

Proc Natl Acad S 95,5341

Epilepsiebeginn in Adoleszens

Clin Nruophysiol 28,642

Management of extremely preterm infant: is the replacement of estradiol and

progesterone beneficial?

Trotter A., Maier L, Pohlandt F.

Section of Neonatology and Peadiactric Critical Care Medicine, Children´s Hospital,

University of Ulm, Germany

GABA - Rezeptor

Progesteron GABA

Dia

ze

pa

m

Barbiturate

Pro

ge

ste

ron

-M

eta

bo

l ite

n

GABA

Dia

ze

pa

m

Barbiturate

Pro

ge

ste

ron

-M

eta

bo

l ite

n

GABA

Rezeptor

Gehirn – Lunge Konnex

Gammaaminobuttersäure (GABA)

Progesteronmetabolite

GABA

Rezeptor

Anxiolyse Schleimsekretion

Nat Med. 2007 Jul;13(7):777-8.

Corry DB et al. Nat Med. 2007 Jul;13(7):777-8.

Regulation of goblet cell metaplasia during

allergic airway inflammation

Östrogene vermehren

die LDL Rezeptoren und

Verbessern damit die

Lipidaufnahme in die

Zelle - damit sinkt der

Periphere Cholesterinspiegel.

Die Östrogenbehandlung der

menopausalen Hyper-

cholesterinämie stellt eine

kausale Therapie da.

Bei einer problematischen

Polymorphismuskonstellation

erweist sich ein Umsteigen auf

Statine sinnvoll.

Lipidsenker

unter 40 J.

4% 40-54 J.

20%

55-64 J.

34%

65+ J.

42%

Alterstruktur Männer

(7,3 Mio. Verordnungen) unter 40 J.

2%

40-54 J.

9%

55-64 J.

27%

65+ J.

62%

Alterstruktur Frauen

(7,2 Mio. Verordnungen)

Quelle: IMS Health, VIP

76%

24%

89%

11%

bis 54

ab 54

bis 54

ab 54

% o

f P

op

ula

tio

n

0

20

100

40

60

80

20-29 30-39 40-49 50-59 60-69 Ages (years)

6 6

13 8

29

17

45 45

59 58

Males

Females

Estimated US prevalence of cardiovascular diseases by age

and sex

Peter W.F.Wilson et al Am J Kidney Dis, Vol 32, 5, 56 1998

LDL Rezeptor Expression nimmt im Alter ab

Lee HC, Paz MA, Gallop PM.

Low density lipoprotein receptor ibnding in aging human diploid fibroblasts in

culture.

J Biol Chem 1982 Aug 10;257(15):8912-8

Field PA, Gibbons GF.

Decreased hepatic expression of the low-density lipoprotein (LDL) receptor

and LDL receptor-related protein in aging rats is associated with delayed

clearance of chylomicrones from the circulation

Metabolism 2000 Apr;49(4):492-8

Women and cardiovascular risk.

Welty FK. Beth Israel Deaconess Medical Center, Boston, USA

Am J Cardiol 2001 Oct 11;88(7 Suppl 2):48-52

„Menopause is associated with significant elevations in serum cholesterol levels and a

3-fold increase in the risk of CAD.“

NITROPRÄPARATE SIND

NO DONOREN

ÖSTRADIOL IST EIN

NO INDUKTOR

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

Während der Schwangerschaft Unter den Wehen

Während der Schwangerschaft Unter den Wehen

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

NO

Während der Schwangerschaft Unter den Wehen

Endotheliale Stickstoff Synthase (NOS3)

5'

+1

T>C pos-786

ATG

Translation

Promoter 3'

Glu>Asp Codon 298

Exon 7Promoter Intron 4

Ins>Del

polymorphic 287 bp insertion/deletion sequence

5‘ 3‘

INTRON 16 of the ACE gene

Angiotensin I-Converting Enzym (ACE)

Polymorphism: Ins/Del (287bp) in Intron 16

Angiotensin converting enzyme (ACE) plays an

important role in blood pressure regulation and

electrolyte balance by hydrolyzing angiotensin I into

angiotensin II. Angiotensin II is a potent vasopressor,

and aldosterone-stimulating peptide, maintaining

cardiovascular homeostasis. The human ACE

geneharbors an insertion (I) / deletion (D) polymorphism.

The D/D genotype is associated with high plasma levels

of ACE leading to increased angiotensin

IIconcentrations. This is reflected in higher genetic

predisposition for hypertension.

polymorphic 287 bp insertion/deletion sequence

INTRON 16 of the ACE gene

Renin-Angiotensin-Aldosteron-System

• Plasmavolumen

•Sympath. Nervensystem

•Blutdrucksenkung

•Natriumentzug

EE/E2

Östrogene Cortisol, Cortison

• Glatte Gefäß-

muskulatur

- Vasokonstriktion

- Blutdruckerhöhung

• Erhöhung der Nor-

adrenalinfreisetzung

• Wirkung auf ZNS

zentrale

Blutdruckerhöhung

• Metabolische Effekte

Leber

Pro-Renin

Renin

Niere

ACTH

Angiotensinase

Prog.

Wasser- und

Natriumretention

Angiotensinogen

Angiotensin

I ACE II

Nebennierenrinde Aldosteron

Antirheumatika

unter 30 J.

12%

30-39 J.

14%

40-54 J.

24%55-64 J.

21%

65+ J.

29%

Alterstruktur Männer

(22 Mio. Verordnungen)

Alterstruktur Frauen

(32 Mio. Verordnungen) unter 30 J.

9%

30-39 J.

9%

40-54 J.

19%

55-64 J.

18%

65+ J.

45%

Quelle: IMS Health, VIP

50%50%

63%

37%bis 54 ab 54 bis 54

ab 54

Gender-spezifische Erkrankungen Antigene

Addison´s disease 21-hydroxylase

Coeliac disease Tissue transglutaminase

Type 1 diabetes GAD-65, insulin, IA-2A

Graves´hyperthyroidism Thyroid-stimulating-

hormone receptor

Hashimoto´s thyroiditis Thyroid peroxidase,

thyroglobulin

Myasthenia gravis Acetylcholine receptor

Goodpasture´s syndrome TypeIV collagen

Pemphigus vulgaris Desmoglein 3

Pernicious anaemia H/KATPase, intrinsic factor

Primary biliary cirrhosis E2 PDC

Vitiligo Tyrosinase, SOX-10

Multiple sclerosis Myelin basic protein, myelin

oligodendritic glycoprotein

REZ I Bk a

I Bk a

I Bk a

NF Bk

NF Bk NF Bk

REZ

REZ

DIAMINOXYDASE IN

EXTRAUTERINEN ORGANEN

DURCH ÖSTROGEN GEHEMMT:

URTIKARIA

RHINITIS

LIDÖDEM

REIZDARM

DYSMENORRHOE

E2

Coll Antropol 1998 Dec;22(2):393-402

Body composition characteristics after menopause.

Kirchengast S, Grossschmidt K, Huber J, Hauser G

Maturitas 1996 Feb;23(1):63-71

Decreased sexual interest and its relationship to body build in postmenopausal women.

Kirchengast S, Hartmann B, Gruber D, Huber J

Maturitas 1998 Jun 17;29(3):253-9

Effect of percutaneous androgen replacement therapy on body composition and body weight in

postmenopausal women.

Gruber DM, Sator MO, Kirchengast S, Joura EA, Huber JC

TESTOSTERONE, SEX HORMONE-BINDING GLOBULIN, AND THE

DEVELOPMENT OF TYPE 2 DIABETES IN MIDDLE-AGED MEN:

PROSPECTIVE RESULTS FROM THE MASSACHUSETTS MALE AGING

STUDY.

Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB.

New England Research Institutes, Watertown, Massachusetts, USA.

Diabetes Care 2000 Apr; 23(4):490-4

Menopause Int. 2010 Dec;16(4):162-8.

Menopause and sexual desire: the role of testosterone.

Nappi RE, Albani

Preclinical data obtained in experimental rats show that androgens made

from DHEA in the vagina are beneficial to collagen formation in

the 3 layers of the vagina namely the epithelial layers, the lamina

propria and muscularis

Menopause. 2009 Sep-Oct;16(5):907-22. doi

:

Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly

efficient treatment of vaginal atrophy.

Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez JL, Girard G,

Baron M, Ayotte N, Moreau M, Dubé R, Côté I, Labrie C, Lavoie L, Berger L,

Gilbert L, Martel C, Balser J.

OBJECTIVE:

Because the secretion of dehydroepiandrosterone (DHEA), the exclusive

source of sex steroids in postmenopausal women, is already decreased by

60% and continues to decline at the time of menopause, the objective of this

study was to examine the effect of intravaginal DHEA on the symptoms and

signs of vaginal atrophy.

METHODS:

This prospective, randomized, double-blind and placebo-controlled phase III

clinical trial studied the effect of Prasterone (DHEA) applied locally in the

vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal

women.

Labrie and colleagues reported no change

in atrophic endometrium at the end of their

12 week randomised trial of DHEA

administered intravaginally The lack of

effect of DHEA on the endometrium is

thought to be due to the absence of the

enzymes required to convert DHEA to

estrogens in the endometrium itself.

Women were randomised to placebo, 0.25% (3.25

mg), 0.5% (6.5 mg) or 1.0% (13 mg) vaginal cream

daily. Vaginal atrophy was reversed with minimal

changes in serum steroid hormone levels, which

remained within the normal postmenopausal range .

Beneficial effects on four aspects of sexual

dysfunction, desire/interest, arousal, orgasm, and

dyspareunia were reported for this study. These data

suggest that local combined androgenic/estrogenic

stimulation in the vagina may exert favourable effects

on vaginal atrophy and hence improved sexual

function. The data from thisstudy were re-analysed

separately for each of the 7 centres involved

in demonstrating a consistent beneficial effect of

treatment on vaginal atrophy between all centres

The exceptionally high consistency between all

sites in this phase III study and high potency of

the compound permit to obtain a clinically and

statistically significant to highly significant

effect of treatment on all parameters of vaginal

atrophy with the 0.5% DHEA daily intravaginal

dose which does not significantly affect the

serum levels of oestrogens, thus avoiding

systemic risks.

In OVX animals, the lamina propria area was decreased to 44%, an effect

which was reversed by DHEA to 69% of the intact value. OVX also caused a

59% decrease in the area of PGP 9.5 fibers, an effect which was prevented

by DHEA, thus showing a 68% stimulatory effect of DHEA on the density of

PGP 9.5 fibers in the lamina propria compared to OVX animals. Following

OVX, the muscular layer area was decreased by 61%. DHEA treatment

induced 118% and 71% increases in TH fiber area compared to OVX and

intact animals, respectively. The density of TH fibers was 182% increased

over intact controls by DHEA treatment of OVX animals.

Conclusions. The relatively potent stimulatory

effect of DHEA on intravaginal nerve fiber density

provides a possible explanation for the beneficial

effects of intravaginal DHEA on sexual dysfunction

observed in postmenopausal women.

Pelletier G, Ouellet J, Martel C, and Labrie F. Effects of ovariectomy and

dehydroepiandrosterone (DHEA) on vaginal wall thickness and innervation.

J Sex Med 2012;9:2525–2533

A synthetic form of OT used to facilitate

breastfeeding was linked to increased sexual

desire and vaginal lubrication ( [Anderson-

Hunt and Dennerstein, 1994] and [Anderson-

Hunt and Dennerstein, 1995]). Indeed, these

authors reported the case of a woman who

about 2 h after the use of a synthetic OT

spray noticed copious vaginal transudate and

a subsequent intense sexual desire.

Furthermore, in the same woman, a higher

amount and intensity of uterine and vaginal

contractions were intensified at orgasm along

with heightened subjective pleasure

(Anderson-Hunt and Dennerstein, 1994).

These observations seem to suggest that OT

can produce some effects due to its ability to

stimulate the contraction of smooth muscles

in the genital-pelvic area.

Anderson-Hunt and Dennerstein, Increased female sexual response after

oxytocin BMJ, 309 (1994), pp. 309–929

In a double-blind, randomized, placebo-controlled, between-subject

design, we tracked the eye movements of 52 healthy male volunteers

who were presented with 24 neutral human faces after intranasal

administration of 24 IU oxytocin or placebo.

Results

Participants given oxytocin showed an increased number of fixations and

total gaze time toward the eye region compared with placebo

participants.

With regard to steroid hormone levels, we observed an increase of

testosterone plasma levels 3.5 h after OXT administration.

The data may help to gain a better understanding of the

pharmacokinetics of OXT in humans, and bring attention the possible

role of testosterone as indirect modulator of behavior after

OXT administration.

Results. Oxytocin positively impacted a number of components of

sexual function, including libido, erection, and orgasm, and was well

tolerated

In conclusion, these results indicate that OT treatment evokes

MSCprotectionthroughbothintrinsicpathwaysandsecretion of

cytoprotective factors.Exvivo cellular treatment with OT represents an

attractive strategy aimed to maximize the biological and functional

properties of effector cells. (Endocrinology 153: 5361–5372, 2012)

100

140

180

220

260

2 4 6 8 10 12 14 16

Jahre nach der Menopause

unter Östrogentherapie

ohne Behandlung

Kolla

ge

ngeh

alt

der

Ha

ut

Maturitas. 1987 Apr;9(1):1-5.

Skin collagen changes in post-menopausal

women receiving oestradiol gel.

Brincat M, Versi E, O'Dowd T, Moniz CF, Magos A, Kabalan S, Studd JW.

100

140

180

220

260

2 4 6 8 10 12 14 16

Jahre nach der Menopause

unter Östrogentherapie

ohne Behandlung

Kolla

ge

ngeh

alt

der

Ha

ut

estrogen

Lancet. 1999 Jul 17;354(9174):224

Lancet. 1999 Jul 17;354(9174):224

The number of people aged 60 years and older is growing rapidly worldwide. So

keeping the elderly healthy has to be high on the list of priorities. Ageing research is

clearly gaining momentum, as the reviews in this Insight testify, bringing hope that at

some time in the future we will be able to keep age-related diseases at bay by

suppressing ageing itself. As ageing will affect us all sooner or later, we hope that you

will find this collection informative and stimulating.

Gynecol Endocrinol. 2002 Dec;16(6):431-41 .

Current concepts in aesthetic

endocrinology.

Gruber CJ, Wieser F, Gruber IM, Ferlitsch K, Gruber DM,

Huber JC.

Ann Chir Gynaecol Suppl. 1987;202:39-41.

Local oestriol treatment improves the

structure of elastic fibers in the skin of

postmenopausal women.

Punnonen R, Vaajalahti P, Teisala K.

Br J Obstet Gynaecol. 1995 Dec;102(12):985-9.

The effect of topical oestradiol on skin

collagen of postmenopausal women.

Varila E, Rantala I, Oikarinen A, Risteli J, Reunala T, Oksanen H, Punnonen R.

100

140

180

220

260

2 4 6 8 10 12 14 16

Jahre nach der Menopause

unter Östrogentherapie

ohne Behandlung

Kolla

ge

ngeh

alt

der

Ha

ut

J Am Acad Dermatol 2005;53:555-68

Maturitas. 1994 Nov;20(1):25-30.

Treatment of skin ageing symptoms in

perimenopausal females with estrogen

compounds. A pilot study.

Schmidt JB, Binder M, Macheiner W, Kainz C, Gitsch G, Bieglmayer C.

Gynecol Endocrinol. 2001 Dec;15 Suppl 6:18-21.

Immunological and dermatological impact of

progesterone.

Huber J, Gruber C.

Ann NY Acad Sci 548:66-84

J Invest Dernatol 103:60-64

J Invest Dermatol 99:415-

421

J Invest Dermatol 98 (6):895-

901