Teleconferencia con Ginebra
Q: Third versus first generation progestogens for contraception
Few data from randomised controlled trials are available
Venous thromboembolic disease (DVT; Pulmonary
embolism)[1]:
case-control, multicentric study (Africa, Europe, Latin America):
Table 1: Adjusted odds ratios of venous thromboembolism in relation to current use of combined OCs by progestagen type and estrogen dose
| Progestagen | E<50mcg | E>/=50mcg |
| First generation | 3.37 (1.44-7.93) | 4.05 (1.92-8.54) |
| Second generation | 3.61 (2.53-5.13) | 3.83 (2.44-6.02) |
| Third generation | 7.36 (4.20-12.90) | N/A |
ORs relative to non-users in Europe
adapted from: Venous thromboembolic disease
and combined oral contraceptives: results of international multicentre
case-control study. World Health Organization Collaborative Study of
Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995 Dec
16;346(8990):1575-82.
Thromboembolic stroke
220 cases/775 controls; OC associated risk was slightly higher for first generation than for second or third generation progestogens [2]
Ischaemic stroke
RATIO-study [3]
large case - control study; multicentric; (Netherlands)
(a) first-generation oral contraceptives, containing lynestrenol or norethindrone; (b) second-generation oral contraceptives, containing norgestrel or levonorgestrel; (c) third-generation oral contraceptives, containing desogestrel or gestodene; and (d) oral contraceptives containing other types of progestogens (ie, norgestimate, cyproterone acetate, and medroxyprogesterone acetate [used in progestogen-only preparations]
Table2: ORs (95% CI) for Ischemic Stroke in Relation to Different Types of Progestogens*
| OR* (95% CI) | Adjusted OR**(95% CI) | |
| Any current OC use | 2.3 (1.6–3.3) | 2.1 (1.5–3.1) |
| First-generation OC use (lynestrenol of norethindrone) | 1.7 (0.7–4.4) | 1.8 (0.7–4.7) |
| Second-generation OC use (levonorgestrel) | 2.4 (1.6–3.7) | 2.1 (1.3–3.3) |
| Third-generation OC use (desogestrel or gestodene) | 2.0 (1.2–3.5) | 2.3 (1.3–4.2) |
| Other+ | 2.0 (0.8–4.8) | 1.5 (0.6–4.0) |
ORs are relative to nonusers: 101 patients and 568 control women
*Adjusted for stratification factors (age, area of residence, and calendar
year).
**Adjusted for stratification factors, hypertension, diabetes mellitus,
hypercholesterolemia, smoking, and alcohol use.
+Including OCs containing cyproterone, norgestimate, and progestogen only.
source: Kemmeren JM, Tanis BC, van den Bosch MA, Bollen EL, Helmerhorst FM, van der Graaf Y, Rosendaal FR, Algra A. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Study. Oral contraceptives and the risk of ischaemic stroke. Stroke. 2002 May;33(5):1202-8.
Acceptability: Cochrane systematic review
discontinuation, side effects similar both groups for mono-and multiphasic
preparations [3]
References:
1)[No authors listed]. Venous thromboembolic disease
and combined oral contraceptives: results of international multicentre
case-control study. World Health Organization Collaborative Study of
Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995 Dec
16;346(8990):1575-82.
[PubMed]
2)Heinemann LA, Lewis MA, Spitzer WO, Thorogood M,
Guggenmoos-Holzmann I, Bruppacher. Thromboembolic stroke in young
women. A European case-control study on oral contraceptives. Transnational
Research Group on Oral Contraceptives and the Health of Young Women.
Contraception. 1998 Jan;57(1):29-37 [PubMed]
3) Kemmeren JM, Tanis BC, van den Bosch MA, Bollen EL, Helmerhorst FM, van
der Graaf Y, Rosendaal FR, Algra A. Risk of Arterial Thrombosis in Relation
to Oral Contraceptives (RATIO) Study. Oral contraceptives and the risk of
ischaemic stroke. Stroke. 2002 May;33(5):1202-8. [PubMed]
4)Kulier R, Helmerhorst FM, Maitra N,Gülmezoglu AM.
Effectiveness and acceptability of progestogens in combined oral
contraceptives - a systematic review. Reprod Health. 2004 Jun 3;1(1):1[PubMed]
Q: Combined oral contraceptives and breast cancer
An increased relative risk (RR) of 1.24 of having breast cancer diagnosed whilst on any COC decreasing during the 10 years after stopping.
The disappearance of any increased risk, compared to non-users, 10 years after stopping the COC.
Cancers in users were less clinically advanced, but there was no data on mortality.
A family history of breast cancer, duration of use, age at first use and the dose and type of hormone had no additional effect on the risk of having breast cancer once length of time since last use had been taken into account.
Table 3: The relative risk of having breast cancer diagnosed in relation to COC use
| COC Usage | Relative Risk | Significance |
| Current users | 1.24 | p<0.00001 |
| 1-4 years after stopping | 1.16 | p<0.00001 |
| 5-9 years after stopping | 1.07 | p<0.009 |
| 10+ years after stopping | 1.01 | Non significant |
Source: Faculty of Family Planning Statement on Breast Cancer, 1996, adapted from: Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives. Lancet 1996; 347: 1713-27.
References:
Faculty of Family Planning
and Reproductive Health Care of the RCOG:
Combined
oral contraception and cancer - review
Other useful sites:
PGC 2004 - Oral Contraceptives
WHO - Medical Eligibility Criteria for Contraceptive Use
PGC 2004 - Emergency contraception
Cochrane systematic review: Cheng L,
Gülmezoglu AM, Van Oel CJ, Piaggio G, Ezcurra E, Van Look PFA. Interventions
for emergency contraception (Cochrane Review). In: The Cochrane Library,
Issue 4, 2004. Chichester, UK: John Wiley & Sons, Ltd. [PubMed]
Reference:
Peter Jüni, Linda Nartey, Stephan Reichenbach, Rebekka Sterchi, Paul A Dieppe, Matthias Egger. Risk of cardiovascular events and rofexcoxib: cumulative meta-analysis. Lancet. November 5th 2004. Published online at http://www.lancet.com
Edited by Aldo Campana,