Today it is well known that CSP has a similar tolerability and rate of effects as oral contraceptives . For example, the CSP increases TC, HDL-C, TG, and decreases LDL-C . The CSP also induce non-adverse effects on the carbohydrate metabolism and liver function tests . Furthermore, it has been proven that the CSP may induce changes in the blood coagulation system [18, 19]. Other common adverse effects include skin reactions at the site of application, breast discomfort during the first two cycles, and dysmenorrhea . Nausea, emotional lability, headache, and occasional breakthrough bleeding are less frequently reported [21, 22]. Effects of the SCI on most metabolic variables and on the blood coagulation system do not seem relevant [23–27]. Headache and dyspnea are frequent complaints , and a low rate of anxiety/depression (1-9%) has been reported . Nausea, breast tenderness, lower abdominal pain, loss of libido, and fatigue are infrequent symptoms . Weight gain has not consistently been associated with either CSP or SCI.
One hundred Mexican women were screened prior to entering a contraception program. In the CSP group, women were students, professionals, and housewives, whereas in the SCI group all users were homemakers. Despite these differences, the clinical characteristics were homogeneous between groups except for age because users of the CSP were younger.
Almost 30% of women were excluded from this study. Most were enrolled in the CSP group. We do not have a clear explanation for this finding. Perhaps the younger age of women in this group or the ease for withdrawal from the method determined this fact. A relatively low number of women were screened at the end of the 4-month study period in the CSP group. In the SCI group we were able to complete the study with 80% of the women originally enrolled. In this last group, only one user required withdrawal of the device 2 months after starting the study due to severe hemorrhage. After the 4-month study period, 30% of women in the SCI group had secondary effects.
Regarding laboratory abnormalities, the CSP slightly modified the metabolic variables analyzed but most of these changes were not clinically significant. Among the SCI users, changes were more evident but in some cases could be considered as beneficial. We observed a decrease in glucose concentration, a fact without a clear explanation. We may hypothesize that the increase of IGF-1 may be responsible for this phenomenon as previously suggested . Indeed, in type 2 diabetic patients, IGF-1 glucose levels and insulin requirements are lower . Moreover, in nondiabetic patients, IGF-1 increases insulin sensitivity and glucose metabolism while suppressing lipolysis and postprandial lipemia . Although the increase in serum levels of IGF-1 may partially explain the changes in glucose metabolism, we must underline that this phenomenon does not appear to be a risk factor for contraceptive users.
On the other hand, the AI decreased and, of course, this is a finding that may suggest a positive relationship between the risk of atherothrombotic disease and the use of SCI. As described for the CSP, we also observed a significant decrease of IB. Previous studies evaluating the effects of SCI reported an increase of IB, hemoglobin, and hematocrit due to either the presence of amenorrhea or to the low frequency of hemorrhage [32–34]. In this study amenorrhea was infrequently observed but hemorrhage was a predominant symptom, a fact that may explain the decrease of IB levels. According to the thyroid and liver function tests, we observed minimal changes, only being significant for LDH, GGT, and TSH. These changes cannot be considered as adverse effects because the levels were always within normal ranges. Fortunately, this pattern of non-adverse effects remains similar when the SCI is used for longer periods of time .
Leptin and adiponectin, two cytokines that regulate metabolism, have gained attention in recent years due to their relation with other pathophysiological states. Low levels of adiponectin are associated with obesity, insulin resistance, and type 2 diabetes mellitus  as well as atherosclerosis, high blood pressure and coronary artery disease . Moreover, a low adiponectin level is a strong risk factor for the development of metabolic syndrome . On the other hand, leptin levels are not only associated with the amount of fat accumulated but also the energy balance of an individual. Abnormal leptin levels significantly influence the metabolic and hormonal processes in the organism . High plasma levels of this cytokine are associated with obesity, insulin resistance, and glucose intolerance. These last two entities are strongly associated with the development of diabetes . On these bases, we considered important to evaluate these cytokines before and after the treatment. However, we did not find significant changes in either CSI or CSP users. Adiponectin levels remained almost unchanged, whereas leptin showed minimal changes, especially in CSP users.
In order to determine if the metabolic changes may be related to the presence of an inflammatory state, we assayed the hsCRP, a very sensitive acute phase reactant for these purposes [41, 42]. After 4 months, levels of this protein significantly rose only in the CSP group, up to almost 50% compared to basal levels. These data differ from previous reports in which hsCRP rose 220% after 2 months of SP use , a fact that suggests that the CSP may be associated with an important pro-inflammatory state only during the beginning of contraceptive therapy.
Due to the high mestizage of our population, we attempted to present a representative sample of Mexican women and to determine their overall metabolic response to contraceptive therapy. Although with modern techniques it is possible to establish the genetic background of an individual, it is accepted that sociocultural criteria and the presence of blood group O have sensitivity and specificity levels high enough to consider an individual as indigenous . On the contrary, to identify a mestizo woman is quite simple after analyzing the phenotype of the individual and after interrogation about the origin of the user. To our knowledge, this is the first attempt to evaluate the metabolic effects of contraceptives in native-American populations. Eighteen indigenous women who were treated with SCI completed the study and the analysis of the metabolic changes induced by this contraceptive method showed that they had only slight differences as compared with mestizo women. Unfortunately, this analysis was not possible for the CSP group because none indigenous woman choose the CSP. Therefore, our results strongly suggest that at least the SCI does not induces clinical or biochemical relevant changes in either indigenous or mestizo Mexican women.
Of course, this study has some limitations. First, the non-randomized design of the research may be considered a major pitfall and a source of biased results however, considering that all around the world women chose the contraceptive method they desire to use, it was impossible to perform this study with a randomized design. Second, we are aware of our small sample a fact that may have some impact on the conclusions of the study. However, it must be stated that most of the literature addressing the secondary effects of contraceptive treatments include similar numbers of patients.