Progestogens of varying androgenicity and cardiovascular risk factors in postmenopausal women receiving oestrogen replacement therapy.
OBJECTIVE
Medroxyprogesterone (MP) was used as the progestogen in randomized clinical trials of postmenopausal hormone replacement on cardiovascular risk. To attempt to understand the lack of benefit in these trials, we have examined the effects of MP and two other progestogens, the less androgenic desogestrel (DG) and the more androgenic norethisterone (NE), on cardiovascular risk factors against a background of oestrogen therapy.


METHODS
Thirty-four women were treated with conjugated equine oestrogens (CEE) 0.625 mg daily alone for 12 weeks, followed in random order by each of the three progestogens (DG 75 microg, MP 10 mg and NE 1 mg daily) given sequentially for three 12-week cycles while maintaining the same CEE treatment. We measured serum lipoproteins, paraoxonase activity, C-reactive protein (CRP), fibrinogen, fasting glucose and insulin levels at baseline, at the end of the oestrogen-only phase and at the end of each of the combined oestrogen and progestogen phases.


RESULTS
The addition of progestogens to CEE maintained the oestrogen-induced reduction in apolipoprotein B (apo B) and lipoprotein (a) [Lp(a)], and further lowered total cholesterol (P < 0.01) and fibrinogen (P < 0.001). CEE raised serum triglyceride (P < 0.001) and CRP (P < 0.01) concentrations, which reverted towards pre-oestrogen levels with progestogens. Progestogens significantly reduced high density lipoprotein (HDL) cholesterol (P < 0.05). NE was associated with the greatest reduction in HDL cholesterol and apo A1, but was most effective in preserving paraoxonase activity and reducing the potentially unfavourable oestrogen-induced increases in triglycerides and CRP.


CONCLUSIONS
Preconceptions that more androgenic progestogens necessarily have more unfavourable effects on cardiovascular risk factors may require revision.
Kwok
See
S
Barlow Medical Center, Manchester, UK. sk7@doctors.org.uk
Selby
Peter L
PL
McElduff
Patrick
P
Laing
Ian
I
Mackness
Bharti
B
Mackness
Michael I
MI
Prais
Hilary
H
Morgan
Janet
J
Yates
Allen P
AP
Durrington
Paul N
PN
Sci
F Med
FM
D043303:Aryldialkylphosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D017135:Desogestrel / Q000627:therapeutic use; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008525:Medroxyprogesterone / Q000627:therapeutic use; D008875:Middle Aged; D009640:Norethindrone / Q000627:therapeutic use; D017698:Postmenopause / Q000097:blood*; D011372:Progestins / Q000627:therapeutic use*; D012307:Risk Factors; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D011372:Progestins; D014280:Triglycerides; D017135:Desogestrel; D005340:Fibrinogen; D002097:C-Reactive Protein; D043303:Aryldialkylphosphatase; D008525:Medroxyprogesterone; D009640:Norethindrone