Giorn. It. Ost. Gin. Giornale Italiano di Ostetricia e Ginecologia CIC Edizioni Internazionali 2014 March-April; 36(2): 317–321. ISSN: 0391-9013
Published online 2014 May 30.

Recommendations for contraception in women with diabetes. AMD-SIC position paper

P. BIANCHI

For the Woman Group of Diabetes Association (AMD)

A. CAGNACCI

For the Italian Society for Contraception (SIC)

 

In the last 35 years new contraceptive methods have been developed. In the field of hormonal contraception, evolution has led to the progressive reduction of oestrogen doses from over 50 mcg to 15 mcg of ethynyl-estradiol (EE) dose, and the substitution of EE with estradiol. A new route of administration, different regimens and progestin only contraception have been developed. Varied side effects, such as increase in body weight, water retention, nausea, vomiting, and an increased risk for cardiovascular and thrombo-embolic events were associated with the use of old oral hormonal contraceptives. These effects, that can be exacerbated by the woman’s lifestyle and by co-morbidities, have been progressively reduced by the use of oral hormonal contraceptives containing lower EE doses, or by progestin only contraception The Medical Eligibility Criteria for Contraceptive Use (MEC) (1) contains indications and contraindications for the use of the following methods of contraception:

  • Combined Oral Contraceptives with low hormonal doses
  • Copper intra-uterine device (cu-IUD)
  • Levonorgestrel intrauterine device (LNG-IUD)
  • Injectable Hormonal Contraceptives
  • Transdermal Patch contraceptive
  • Vaginal Ring Contraceptive
  • Progestin only contraception performed by either oral, injective or sub-cutaneous route.

In spite of the marked improvement in the hormonal contraceptive safety, some risks are still linked to the use of hormonal contraception (1). The “strenghts” of a contraceptive pertains not only to its efficacy and safety, but also to its acceptability, easy to use, reversibility and tolerability. Acceptability is a key factor for the use of a given method, for its continuation and ultimately for its real contraceptive efficacy. In addition, hormonal contraceptives provide numerous extra-contraceptive benefits (Table 1).

TABLE 1TABLE 1
NON-CONTRACEPTIVE BENEFITS OF HORMONAL CONTRACEPTIVES.

Planning a pregnancy in a diabetic woman

In diabetic women planning a pregnancy in a period of optimal metabolic control is critical in reducing foetus and newborn morbidity and mortality (2, 3). It seems that diabetic women are well aware of the risk associated with an unplanned pregnancy. In 2005 an Italian study performed in 667 diabetic women, revealed that 89.3% of them were actually using contraceptive methods (30.4% oral hormonal contraception; 12.0% IUD; 47.0% natural or barrier methods). These figures are much higher than those present in the general population of fertile women in Italy (4).

Safety parameters for hormonal contraception in women with diabetes

In order to define the safety of a hormonal contraceptive in a woman with diabetes it is mandatory to know the impact that hormonal contraceptive exerts on:

  • Coagulation and in particular the risk of thrombosis
  • Metabolism and in particular carbohydrate metabolism.

These aspects are critical because the hormonal contraceptive may impact on the course of diabetes, of its complications, and even accelerate metabolic abnormalities in women with a genetic predisposition of developing diabetes, such as those women having suffered from gestational diabetes (5, 6).

Metabolic modification and contraception

As expected the use of IUD or LNG-IUD does not impact on metabolism and coagulation. Accordingly, IUD and LNG-IUD can be safely used in women with diabetes. The use of these methods in women with diabetes is not associated with an increased risk of pelvic inflammatory disease, bleeding or other inconveniences. There is no restriction (category 1 of MEC) and advantages are superior to disadvantages (category 2 of MEC) for the use of IUD and LNG-IUD in diabetic women (Table 2). In some cases the use of progestin only contraceptives may lead to a subtle (7) clinically insignificant (8) reduction of insulin sensitivity. No major metabolic alteration nor and increased cardiovascular risk was evidenced during the 2 year use of the subdermal implant of etonorgestrel (9). Decreases of insulin sensitivity, even in the absence of fasting glucose modification, are associated with the use of combined hormonal contraceptives containing androgenic progestins. These effects are not evident with the use of compounds containing anti-androgenic progestins (10), or with the vaginal ring (11). A 2012 Cochrane Review (12) on the role exerted by hormonal contraceptives in the control of carbohydrate metabolism of non-diabetic women concluded by examining 16 adequate studies:

  • Overall, hormonal contraception has a low impact on carbohydrate metabolism
    TABLE 2TABLE 2
    WHO RECOMMENDATION FOR THE USE OF DIFFERENT CONTRACEPTIVES IN WOMEN WITH DIABETES.
  • Most of the effects are limited in time and comparable among the different formulations
  • Associations containing progestins derived by progesterone should be preferred for a potentially lower impact on carbohydrate metabolism.

The Wisconsin Epidemiological Study (13) reported that in diabetic women the risk of the onset and progression of diabetic retinopathy or hypertension is dependent on the oestrogen dose (high/low dose) and on the length of contraceptive use. In spite of this a Cochrane Review investigating the studies which were published up to 2013 (14), concluded that the evidence is insufficient to define whether or not in women with diabetes hormonal contraception with oestro-progestin or progestin alone has a different impact than non-hormonal contraception on glucose metabolism, lipid metabolism and/or progression of cardiovascular complications.

Prevention of thromboembolism

Deep-vein thrombosis (DVT) is the more relevant among the rare complications, associated with the use of hormonal contraception. This is a very rare event in fertile women. In spite of the absence of incontrovertible data, the rate of DVT in the general population of Italy is estimated to be in 4–7 cases for 10,000 women. Among these cases 1–2 are attributable to hormonal contraception use. Hormonal contraception accounts also for a slight increase in the rate of arterial thrombosis, with an increase of 0.06–0.4 cases/year for 10,000 women. The National Centre for Epidemiology, Surveillance and Promotion of Health, of the National Health Institute, published a document of consensus in 2008 with the aim of guiding counselling for the prescription of hormonal contraception (15). The document was mainly focused on the risk of thrombo-embolism associated with the use of hormonal contraception. It reported that the use of hormonal contraceptives containing third generation progestins (desogestrel or gestodene) had a risk of inducing DVT twice those of hormonal contraceptives containing second generation progestins (levonorgestrel). The document reported that the effect is limited to the first year of use. It was recommended that when a hormonal contraceptive is prescribed a compound with second generation progestin and 20–30 mcg of EE should be preferred. On the other hand, recent data indicate that in comparison to less androgenic progestins, the use of hormonal contraceptives containing levonorgestrel (second generation) is associated with a higher risk of stroke (16). Similarly, in diabetic women use of highly androgenic compounds containing levonorgestrel is associated with the development of microalbuminuria (17). This event does not occur with less androgenic compounds containing third generation progestins (gestodene or desogestrel). These effects on the arterial side are interesting and counteract the concept that second generation progestin should be preferentially prescribed.

It should be pointed out that progestin only contraception does not induce any increase of DVT. Accordingly to the WHO guidelines, progestin only contraception is considered between category 1 and 2 (possible utilization) in thrombophilic women, in individuals with cardiovascular risk factors, and in women with a previous DVT. Use of the progestin only pill, containing desogestrel, is not associated with an increased DVT risk. Indeed, the major risk of DVT with third generation progestin is present only in oestrogen-progestin associations (1, 18).

Contraception in diabetic women

Present recommendation
Presently, the criteria worldwide accepted for the use of a contraceptive in diabetic women are those published by WHO (1). The WHO guidelines define 4 categories of risk for the use of contraceptives in the general population:
  • No restriction of use
  • The advantages associated with the use are superior to the theoretical disadvantages or proven risks
  • This type of contraceptive is contraindicated unless proven advantages are superior to theoretical or proven risks in a given situation
  • Absolute contraindication of use.

Contraceptive indications for diabetic woman are grouped in Table 2.

Some pathologies such as obesity, hypertension, known cardiovascular disease, and dyslipidaemia represent adjunctive cardiovascular risk factor and are more prevalent in diabetic women (Table 3). In diabetic women a chronological age beyond 35 years is a contraindication for the use of oestrogen-progestin combinations, but not for progestin alone. Similarly, after 35 years of age smoking or hypertension are contraindications for the use of oestrogen-progestin combinations, but not for progestin alone. Obesity may decrease the efficacy of some contraceptives (transdermal patch), and may increase the risk of DVT. Accordingly to WHO guidelines, the increase of DVT associated with obesity does not represent a contraindication in the use of oestrogen-progestin combination. Similarly, obesity is not a contraindication for the use of progestin only contraceptives (19, 20).

TABLE 3TABLE 3
WHO RECOMMENDATION FOR THE USE OF DIFFERENT CONTRACEPTIVES IN WOMEN WITH CARDIOVASCULAR RISK FACTORS.

Recommendations for hormonal contraception for women with diabetes

Based on published data, the present recommendations follow the indications published by the WHO guidelines also accepted in the USA (21).

At the first check up of the woman with diabetes some information should be collected:

  • Personal medical history for evaluating absolute contraindication in the use of hormonal contraception
  • Family history of cardiovascular disease at an early age (prior to 50 years of age for both men and women)
  • Years since diabetes onset
  • Diabetic complications
  • Measurement of blood pressure
  • Evaluation of BMI.

Prescription of a hormonal contraceptive in a diabetic woman should follow the following indications:

  • Oestrogen-progestin combinations can be prescribed only in women with diabetes without any vascular complications
  • Progestin only contraception (POP, subcutaneous implant, LNG-IUD) can always be prescribed even in the presence of vascular complications
  • In the presence of comorbidities oestrogen-progestin contraceptives are almost always contraindicated
  • Progestin only contraception (POP, subcutaneous implant, LNG-IUD) can be prescribed even in the presence of comorbidities.

References
1.
World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 4th ed. World Health Organization; 2009. Available from: http://whqlibdoc.who.int/publications/2009.
2.
National Institute for Health and Clinical Excellence (NICE). Management of diabetes from preconception to the postnatal period: summary of NICE guidance. BMJ. 2008;336:714.
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Satpathy HK, Fleming A, Frey D, Barsoom M, Satpathy C, Khandalavala J. Maternal obesity and pregnancy. Postgrad Med. 2008;120:E01–9.
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Cagnacci A, Tirelli A, Cannoletta M, Pirillo D, Volpe A. Effect on insulin sensitivity of Implanon vs. GnRH agonist in women with endometriosis. Contraception. 2005;72:443–6.
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Biswas A, Viegas OA, Coeling Bennink HJ, Korver T, Ratnam SS. Implanon contraceptive implants: effects on carbohydrate metabolism. Contraception. 2001;63:137–41.
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Vicente L, Mendonça D, Dingle M, Duarte R, Boavida JM. Etonogestrel implant in women with diabetes mellitus. Eur J Contracept Reprod Health Care. 2008;13:387–95.
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Cagnacci A, Ferrari S, Tirelli A, Zanin R, Volpe A. Insulin sensitivity and lipid metabolism with oral contraceptives containing chlormadinone acetate or desogestrel: a randomized trial. Contraception. 2009a;79:111–6.
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Cagnacci A, Ferrari S, Tirelli A, Zanin R, Volpe A. Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study. Contraception. 2009b;80:34–9.
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Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. Cochrane Database Syst Rev. 2012;4:CD006133.
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Klein B EK, Klein R, Scot E. Moss Exogenous Estrogen Exposure And Changes In Diabetic Retinopathy: The Wisconsin Epidemiologic Study Of Diabetic Retinopathy. Diabetes Care. 1999;22:1984–7.
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Visser J, Snel M, Van Vliet HAAM. Hormonal versus non-hormonal contraceptives in women with diabetes mellitus type 1 and 2 (Review). Cochrane Database Syst Rev. 2013;3:CD003990.
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Conferenza nazionale di consenso. Prevenzione delle complicanze trombotiche associate all’uso di estro-progestinici in età riproduttiva; Roma. 18–19 Settembre 2008; 2008.
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Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257–66.
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Monster TB, Janssen WM, de Jong PE, de Jong-van den Berg LT, Prevention of Renal and Vascular End Stage Disease Study Group. Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria. Arch Intern Med. 2001;161:2000–5.
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U.S. Medical Eligibility Criteria for Contraceptive Use, 2010; Centers for Disease Control and Prevention (CDC). MMWR Recomm Rep. 2010;59:1–86.
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Society of Family Planning. Research, Research and Leadership; Clinical Guidelines: Contraceptive considerations in obese women Contraception. 2009;80:583–90.
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Lopez, LM.; Grimes, DA.; Chen-Mok, M.; Westhoff, C.; Edelman, A.; Helmerhorst, FM. Hormonal contraceptives for contraception in overweight or obese women (Review) a Cochrane review, by The Cochrane Collaboration and published in The Cochrane Library, by JohnWiley & Sons, Ltd, 2010; Issue 7 http://www.thecochranelibrary.com.
21.
Curtis, KM.; Jamieson, DJ.; Peterson, HB.; Marchbanks, PA. Adaptation of the World Health Organization’s Medical Eligibility Criteria for Contraceptive Use for use in the United States Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. kmc6@cdc.gov. Contraception. 2010. pp. 3–9.