Progestogen-only hormonal contraception linked to metabolic problems in HIV-positive women

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HIV-positive women using progestogen-only hormonal contraception may be at increased risk for negative metabolic outcomes, warned researchers in a recent article in the Journal of Acquired Immune Deficiency Syndromes.

Their longitudinal study of an ethnically diverse United States cohort found that HIV-positive women who took progestogen-only hormonal contraception (HC) had lower fasting high-density lipoprotein (HDL) and higher levels of insulin resistance than HIV-positive women who took the combined contraceptive pill.

This finding is of particular concern because women using progestogen-only contracaptive methods may have chosen this option because they already have risk factors for heart disease.

Glossary

insulin

A hormone produced by the pancreas that helps regulate the amount of sugar (glucose) in the blood.

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

hormone

A chemical messenger which stimulates or suppresses cell and tissue activity. Hormones control most bodily functions, from simple basic needs like hunger to complex systems like reproduction, and even the emotions and mood.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

lipoprotein

Any member of a group of substances containing both lipid (fat) and protein. Lipoproteins are found in both blood plasma and cell membranes. They are the mode of transport for cholesterol through the bloodstream and lymphatic fluid. 

Progestogen-only contraceptive methods may be chosen by women for whom combined contraceptive pills containing both oestrogen and progestogen (also known as progestin in the US) might not be suitable. These include women with a history of blood clots, smokers aged over 35, women with high blood pressure, breastfeeding women and migraine sufferers.

But hormonal contraception is already known to have undesirable metabolic effects in the general population. However, HIV-positive women’s metabolic responses to hormonal contraception have not been closely studied, despite the fact that untreated HIV infection is associated with lower level of 'good' HDL cholesterol, the high rates of raised lipids, diabetes and insulin resistance in people with HIV and the indications of elevated cardiovascular risk in people with HIV.

An additional concern is that two contraceptive methods that lack interactions with antiretrovirals from the non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor drug classes are progestogen-only products, and therefore more likely to be considered suitable for women with HIV.

The study population, which included both HIV-positive and HIV-negative women, was drawn from the multi-city Women’s Interagency HIV Study (WHIS) cohort in the United States.

Researchers looked at five markers of metabolic functioning: fasting HDL, low-density lipoprotein (LDL), triglycerides, glucose and insulin resistance.

The HIV-positive study arm included 86 women using progestogen-only contraceptives; 54 women using combined contraceptives; and 735 women either using non-hormonal contraception or not using contraception.

There are multiple delivery options for progestogen-only and combined contraceptives. HIV-positive study participants using progestogen-only contraception received either levonorgestrel implants (widely known as Norplant) or injections of depot medroxyprogesterone acetate (DMPA, widely known as Depo-Provera). HIV-positive women in the combined HC group used either a pill or patch containing oestrogen and progestogen.

The progestogen-only group had lower HDL levels than either of the other two groups. HDL ('good' cholesterol) helps the body manage LDL ('bad' cholesterol). When the HDL level is too low to offset the LDL level, a buildup of LDL may lead to heart disease.

The progestogen-only group also had higher insulin resistance than the other groups, according to an index known as the homeostasis model assessment estimate of insulin resistance (HOMA-IR).

Insulin is a hormone that breaks down blood sugars. When the blood sugars are not being absorbed properly, the body attempts to compensate by generating more insulin. The term 'insulin resistance' describes this condition, which can be a precursor to diabetes.

Similar patterns were seen for HDL and HOMA-IR in the HIV-negative study arm, which was comprised of 402 women who had similar sociodemographic characteristics and were taking the same types of progestogen-only and combined HC.

The WIHS cohort findings are especially notable because, as the authors say, “HIV disease has been associated with a similar pattern of metabolic dysregulation, and specific antiretroviral drugs may further worsen hypertriglyceridemia, insulin resistance and glucose tolerance”.

In both the HIV-positive and HIV-negative arms of the WIHS study, women taking combination hormonal contraceptives had higher HDL than the other two groups, and their HOMA-IR levels did not vary from those of the others.

While it is recognised that HIV-positive women may have different needs than HIV-negative women in regard to various forms of contraception, the paucity of information about this issue makes it difficult to evaluate HIV-positive women’s contraceptive choices.

The researchers say that more evidence is needed about how progestogen-only contraceptives influence metabolic outcomes in women with HIV, and whether the levonorgestrel-releasing intrauterine device Mirena has less of an impact on metabolic outcomes due to its local, non-systemic mode of action.

References

Womack JA et al. Hormonal contraception and metabolic outcomes in women with or at risk for HIV infection. J Acquir Immune Defic Syndr 52: 581-7, 2009.