The Influence of Oral Contraceptives on Athletic Performance in Female Athletes
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- Burrows, M. & Peters, C.E. Sports Med (2007) 37: 557. doi:10.2165/00007256-200737070-00001
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It is now estimated that the prevalence of oral contraceptive use in athletic women matches that of women in the general population. The oral contraceptive pill (OCP) reduces cycle-length variability and provides a consistent 28-day cycle by controlling concentrations of endogenous sex hormones. The OCP is administered in three different forms that differ widely in chemical constitution and concomitant effects on the human body. As fluctuation in sex steroids are believed to be a possible causal factor in performance and exercise capacity, it is imperative to understand the effect of administering the various types of OCP on women. However, the research into oral contraceptives and exercise performance is not consistent. The type of OCP administered (monophasic, biphasic or triphasic), as well as the type and dose of estrogen and progestogen within, will have varying effects on exercise. To date, research in the area of oral contraceptives and exercise capacity is sparse and much has been plagued by poor research design, methodology and small sample size. It is clear from the research to date that more randomised clinical trials are urgently required to assess the array of OCP formulations currently available to women and their concomitant effect on health and exercise capacity. Therefore, the purpose of this article is to critically appraise the literature to date and to provide a current review of the physiological scientific knowledge base in relation to the OCP and exercise performance. In addition, methodological control, design and conduct will be considered with future areas of research highlighted.
Oral contraceptives are the main form of birth control in the general population and with the introduction of low dose oral contraceptive preparations, their use has increased in athletic women. It is now estimated that oral contraceptive pill (OCP) use in athletic women matches the prevalence of use within the general community. The OCP reduces cycle-length variability and provides a consistent 28-day cycle[1,2] by systematically controlling concentrations of endogenous sex hormones, reducing the natural production of estrogens and progestogens through inhibition of the pituitary secretion of gonadotrophins (figure 1), thus inhibiting ovulation and preventing pregnancy. In addition, oral contraceptives increase cervical mucus production to reduce sperm mobility and reduce the endometrial lining to minimise the likelihood of implantation occurring. However, the OCP is not a single contraceptive agent; it comes in a variety of different types and formulations, which differ widely in their chemical make-up and thus effect on the human body. In addition, the varying doses of estrogen and progestogen in each OCP formulation confer distinct pharmacokinetic properties, which will result in substantial differences in expression. Thus, depending on the type of OCP administered, three to five times more exogenous estrogen and one to two times more exogenous progestogen than the endogenous levels can be provided. As the level and fluctuation of sex steroids are believed to be a possible causal factor in performance,[2,5] it is imperative to understand the effect of administering the various types and forms of OCP on female athletes.
1. The Oral Contraceptive Pill (OCP)
There are basically two main types of OCPs: (i) the combined OCP, which contains both estrogen and progestogen; and (ii) the mini pill, which contains progestogen alone. Most combined OCPs come in 21-day or 28-day pill packages. The 28-day pill pack usually consists of 21 tablets that contain hormones and 7 placebo tablets. However, the progestogen-only pill (POP) or mini pill contains smaller amounts of progestogen compared with the combination pill. The mini pill offers an alternative for women who cannot or do not want to use estrogen-containing oral contraceptives for medical reasons, or for those who are breastfeeding. Because the mini pill does not have estrogen, it tends to have milder adverse effects than combined OCPs.
The combined pill is the most commonly prescribed oral contraceptive and contains two hormones, namely, estrogen and progestogen. Only one synthetic estrogen (ethinylestradiol [EE]) is found in today’s OCPs, compared with one of six major progestogens (levonorgestrel, norethindrone [norethisterone] acetate, desogestrel, norgestimate, norgestrel or etynodiol). It is the EE component of the oral contraceptive that causes the undesirable adverse effects associated with OCP use such as tender breasts and nausea. Conversely, it is also the EE that supports the endometrium, resulting in less intermenstrual bleeding. The progestogens in the OCPs maintain the endometrial lining of the uterus and research indicates that progestogen in the OCP will also oppose the actions of estrogen.[9,10] The form of progestogen used in the OCP will oppose estrogen to varying levels depending on its potency and androgenocity. Potency refers to the power of the progestogen to produce its desired effects and is calculated by multiplying the progestogen dose within the OCP by its progestational activity. Androgenocity refers to the ability of the progestogen to produce masculine characteristics and is calculated by multiplying the progestogen dose within the OCP by its androgenic activity. Each progestogen has a different potency, milligram per milligram, but a higher potency progestogen may be used in a much smaller milligram dose and thus be equivalent to a larger milligram dose of a less potent progestogen (table I and table II). The androgenic relative binding affinity (RBA) of the progestogen is what causes the level of androgenocity. Those with higher androgen RBA lead to more negative adverse effects and counteract the positive estrogen effects to a larger extent. As the more androgenic progestogens oppose the estrogen effects, one would expect the OCPs containing progestogens with higher potency and androgenocity to have a more significant impact on performance then those OCPs containing progestogens with low potency and androgenocity (table I and table II).
The types and doses of steroids are administered to women through three different forms of OCP, namely, monophasic, biphasic and triphasic OCPs. These forms differ according to the steroid doses and timing of such doses across the pill cycle (figure 2). Monophasic pills provide the woman with fixed doses of estrogen and progestogen over 21 days, followed by 7 days of placebo (figure 2 a). Different monophasic formulations contain varying amounts of estrogen and progestogen (table I). In contrast, in a biphasic OCP, the dosage of the hormones is switched once during the 21-day cycle (figure 2 b). Biphasic OCPs have a fixed amount of estrogen, but two different strengths of progestogen between days 7–10 and days 11–14, with the last 7 days being placebos (table II). Triphasic pills contain three different doses of estrogen (or sometimes progestogen) that are increased throughout the cycle (figure 2 c). Depending on the brand, the amount of estrogen may change as well as the amount of progestogen (table II). Given that endogenous production of estrogen and progestogen are suppressed during OCP usage, the serum concentration of active sex steroids is directly related to the OCP dosage administered. Therefore, just as the hormone fluctuations of the menstrual cycle can affect women in different ways, there appears to be a large individual variability between these hormones administered through oral contraceptives and their effects on exercise performance.
2. The OCP and Exercise Performance
Today, mainly monophasic and triphasic OCPs are prescribed, with the use of biphasic OCPs decreasing. As such, only research on monophasic and triphasic OCPs will be presented in this article. The question of the potential effects of OCPs on athletic performance has not been answered conclusively with early controlled trials difficult to interpret because of the diversity in both estrogen and progestogen components of the OCPs used, as well as the range of fitness levels of participants involved (table III). However, given the common use of OCPs in athletes, there may be profound implications for training and competition.
2.1 Body Composition
Progestogen acts as a competitive antagonist at the aldosterone receptor site in the distal tubule of the kidney. During the luteal phase of the menstrual cycle, high concentrations of progestogen result in water and electrolyte loss that stimulates a concurrent increase in aldosterone concentration. Thus, the rapid decline of circulating progestogen on transition from the luteal to follicular phase results in excess aldosterone concentrations leading to the reported premenstrual water and electrolyte retention.
2.1.1 Monophasic Oral Contraceptive Effects
Rosenberg et al. found that fluid retention or the feeling of being bloated was a commonly reported adverse effect of monophasic OCP use containing desogestrel (0.150mg) or gestodene (0.075mg) in moderately active students as a result of the endogenous progestogen concentrations. Increases in water and electrolyte stores have been associated with improved plasma volume maintenance in healthy, inactive women using transdermal patches delivering 17β-oestradiol 0.2mg, in combination with oral ingestion of progestogen (Prometrium® 1) 200mg. Therefore, this could potentially promote buffering capacity and cellular alkalosis, influencing performance.
Notelovitz et al., in a prospective trial on low dose monophasic OCPs (EE 0.035mg + northinedrone 0.4mg), reported that 6 months administration of a monophasic OCP, with a low potency and androgenicity (0.4 + 0.4), increased body mass by 2kg in active women compared with active controls. Such an increase would be detrimental to exercise performance in sports where the extra bodyweight would need to be carried (e.g. running), in aesthetic events where body shape is imperative (e.g. gymnastics) and in weight-classification events where bodyweight determines the competition category (e.g. rowing and weightlifting). The body mass in the study by Notelovitz et al. returned to baseline after 1 month cessation of OCP use, suggesting a causal link between OCP administration and body-mass gain. However, Tantbirojn and Taneepanichskul studied 140 inactive, Thai women in a clinical comparative study of monophasic OCPs (EE 0.035mg + norgestimate 0.250mg, or EE 0.030mg + levonorgestrel 0.150mg), also with a low potency and androgenicity (0.33 + 0.48), and reported no significant difference in body mass over six pill cycles, with a trend for the women to experience a 1.5kg loss in body mass. These differences in findings may be due to the different progestogens in the OCP formulations; the OCPs in the Notelovitz et al. study contained norethindrone, whilst the OCPs in the Tantbirojn and Taneepanichskul study contained norgestimate. However, the potency and androgenicity of the OCP formulations were similar and thus the difference in findings may be more adequately explained by the trained status of the participants, with active women seeing an increase in body mass over 6 months OCP administration, whilst inactive women experience a 1.5kg loss. However, Coney et al., in a large, randomised, placebo-controlled trial on 349 inactive, monophasic OCP users (EE 0.020mg + levonorgestrel 0.10mg), with low potency and higher androgenicity than the previous studies (0.53, 0.83), reported a non-significant gain of ≥1kg in body mass across 6 months of pill use in 40% of women. Thus, in inactive women, the androgenicity of the OCP formulation may be linked with changes in body mass, with higher androgenicity increasing body mass. Yet, Tantbirojn and Taneepanichskul studied 140 inactive, Thai women in a clinical comparative study of monophasic OCPs (EE 0.035mg + norgestimate 0.250mg, or EE 0.030mg + levonorgestrel 0.150mg), with two different OCP formulations; one of a low potency and androgenicity (0.33 + 0.48), and one of a high potency and androgenicity (0.8 + 1.25). They reported non-significant decreases in body mass in both groups over six pill cycles in the order of 1.5kg and 1.1kg loss, respectively, which represents a meaningful difference in an athletic context. Therefore, these findings are varied and produce controversial results. It could be summarised that athletic women may experience increases in body mass due to monophasic OCP use that could be detrimental to performance, whilst inactive women could experience an increase or decrease in body mass due to monophasic OCP use.
2.1.2 Triphasic Oral Contraceptive Effects
The controversial findings are also seen in the triphasic literature. Casazza et al. studied eight active women using triphasic OCPs (EE 0.035mg + norgestimate 0.18/0.215/0.250mg) and found no significant increases in body mass or body fat after one to two cycles of OCP use; however, after 4 months of OCP use, body mass and fat mass significantly increased by 3% and 9%, respectively. This suggests that the OCP effects may not be evident in the short term and that the endogenous hormones may take time to produce the effect on body composition. However, this study used a small sample size, risking a type I error, but the repeated measures and controlled design increases power and, therefore, the results should be acknowledged. In a randomised clinical trial (RCT) by Lebrun et al., trained women using a different triphasic preparation (EE 0.035mg + northinedrone 0.5/1.0/0.5mg) were reported to show short-term effects (over two pill cycles), with significant increases in body mass and percentage of body fat. These results suggest that this triphasic OCP formulation has significant short-term effects on body composition. The differences in findings are probably due to the fact that the OCP preparation in the Casazza et al. study had less progestational and androgenic activity than the formulation utilised in the Lebrun et al., study (table I). This suggests that triphasic formulations with higher progestational and androgenic activity may exert their effect on body composition in the short term, while formulations with lower progestational and androgenic activity take time to exert their effects on body composition. The long-term effects of triphasic OCP have been supported by other studies, in particular, Suh et al. and Jacobs et al., who conducted RCTs on the same triphasic OCP as Casazza et al. (EE 0.035mg + norgestimate 0.18/0.215/0.250mg). Suh et al. and Jacobs et al., reported significant increases in body mass (1.7–2.5%) and percentage of body fat (5.6–10%) due to triphasic OCP use over 4 months and 6 months, respectively, in active women. Thus, triphasic OCPs may increase body mass and fat mass in women and, therefore, be detrimental to performance.
2.1.3 Overall Effect of OCPs on Body Composition
Even though the findings of some studies remain conspicuous as a result of the small sample size, present findings from RCTs suggest that body mass increases or decreases may be dependent not only on the OCP administered, but also on the potency and androgenicity of the progestogen within the OCP. Indeed, if progestogen has independent effects on water regulation via the osmotic regulation of arginine vasopressin, one may suggest that the higher potency and androgenicity of the OCP formulation, the more exacerbated the effects may be. However, more research is needed in this area to test such hypotheses. In addition, one needs to take care when only interpreting significant differences from these studies. This is because some studies report non-significant findings, which may be meaningful in an athletic situation where the athlete relies on minimising body mass (e.g. in gymnastics or distance running).
2.2 Core Body Temperature
2.2.1 Monophasic Oral Contraceptive Effects
It has been hypothesised that the exogenous forms of progestogen in monophasic OCPs can alter thermoregulation in young women by centrally regulating core body temperature and setting the internal threshold temperature at which peripheral heat loss mechanisms are activated. Charkoudian and Johnson reported that in young, inactive women, a range of OCPs formulations shifted baseline core body temperature and the threshold for the active vasodilator system to higher internal temperatures via the effects on central thermoregulatory function. Such shifts are consistent with the prevailing theory that progestogen dominates the effects of estrogen on central thermoregulatory mechanisms. Indeed, Salkeld et al. examined the effects of the OCP on thermoregulation in 18 young, inactive women and reported higher oral temperatures during the active pill days (high progestogen levels) compared with the non-active pill days (low progestogen levels). Taking the research further, Houghton et al. studied the influence of progestogen bioactivity on skin blood flow responses to passive heating in 14 inactive women using a range of monophasic progestogen preparations. Over 6 months of monophasic OCP use, oral temperature was significantly higher during the active pill phase for all participants compared with placebo, but was not affected by progestational bioactivity.
2.2.2 Triphasic Oral Contraceptive Effects
The studies assessing triphasic OCPs and their effect on core body temperature are very limited. Rogers and Baker studied the effects of a range of triphasic OCP formulations in inactive students on core body temperature. The authors found that synthetic progestogens provided by the OCP led to a higher core body temperature due to an increase in thermoregulatory threshold. However, this study had a small sample size of seven subjects, only five of whom were taking triphasic OCPs. Thus, the different hormone levels, potency and androgenicity make reliable conclusions difficult.
2.2.3 Overall Effect of OCPs on Core Body Temperature
No studies have examined the influence of progestogen androgenicity on core body temperature. Thus, so far, it seems that regardless of the progestogen bioactivity within the OCP formulation and the type of OCP used, core body temperature is affected. This is important as core body temperature is associated with performance, particularly in long duration (>60 minutes) events and, thus, any increase in core body temperature due to OCP administration could be detrimental for the athlete. Moreover, not only could it interfere with performance but it could predispose the athlete to an increased risk of heat illness. As such, further studies are needed in this area to clarify the exact OCP influence on core body temperature.
2.3 Metabolism and Substrate Utilisation
Oral contraceptive pills can alter resting lipid and carbohydrate metabolism depending on the ratio of estrogen and progestogen components. Using an animal model, Kendrick and Ellis found that estrogen decreased the amount of glycogen utilisation and increased the availability of lipids during exercise. These findings suggest that athletes could benefit from spared glycogen during performance, if they manage their sex steroid levels. However, studies in human models have produced variable results.[17,20,21,35,45]
2.3.1 Monophasic Oral Contraceptives Effects
The study by Prange-Hansen and Weeke into growth hormone (GH) responses to exercise in inactive women using a monophasic OCP containing norgestimate, found that GH responses to exercise were identical in women during ‘normal’ cycles and OCP cycles. This suggests that the OCP steroids may counterbalance each other resulting in no effect on GH and, thus, substrate metabolism during exercise. Indeed, the progestogen component of the OCP appears to reduce insulin binding and insulin receptor concentration, while the estrogenic component does not appear to have any significant effect. However, more recent studies indicate that inactive women taking monophasic OCPs (containing northinedrone or norgestrel) exhibit higher free fatty acid (FFA) concentrations during exercise and lower carbohydrate metabolism at rest and during exercise than control subjects, signifying increased FFA metabolism by the exercising muscle in those taking monophasic OCPs. This was supported by the McNeil and Mozingo study in inactive women using a monophasic OCP containing norelestrin, where a shift in the mixture of substrates utilised during submaximal work was found, with an increased reliance on triglycerides and a decreased reliance on glycolysis. Such changes in substrate utilisation could be a result of estrogen-GH stimulation of FFA mobilisation and utilisation, resulting in the sparing of muscle glycogen. However, Bemben et al. found no significant differences in fat utilisation in moderately active women using a monophasic OCP containing northinedrone or etynodiol, but a decrease in glucose and carbohydrate metabolism in monophasic OCP users during exercise. They attributed the changes to a stimulation of the hypothalamic glucose receptors by the lower blood glucose levels, or an interaction between the female sex steroids and endogenous opioids.
2.3.2 Triphasic Oral Contraceptive Effects
Jacobs et al. conducted an RCT in five active women using triphasic OCPs (EE 0.035mg + norgestimate 0.18/0.215/0.250mg) and found a significant increase in lipolytic rate but not fatty acid oxidation (resulting in a significant increase in plasma-derived fatty acid re-esterification) during exercise over four pill cycles of OCP use. Cassazza et al. also completed an RCT in eight active women using the same triphasic OCP and reported increased triglyceride mobilisation and plasma cortisol concentration in exercising women, with increased glycerol appearance rates by 20–24%. High concentrations of estrogen and progestogen, typical of the luteal phase, have been shown to induce a glycogen sparing effect,[47,48] both at rest and during exercise, with the concurrent inhibition of gluconeogenesis and glycogenolysis.[48,49] Thus, the decrease in plasma glucose and increase in plasma triglyceride concentrations observed could be due, in part, to a reduction in glucose formation, and increase in glycogen storage in the liver and muscle tissues and, hence, favoured lipid metabolism in OCP users. However, Lebrun et al. studied trained women using a different triphasic OCP formulation (EE 0.030–0.035mg + northinedrone 0.5/1.0/0.5mg) over two cycles and found no significant difference in maximal respiratory exchange ratio (RER) pre and post ovulation. One might suggest that the results may be due to the short-term nature of the study and/or the different OCP formulation used. However, Gillespy et al. studied 15 inactive women over 6–12 months using low-dose triphasic OCP (levonorgestrel and norethindrone) and reported no significant changes in glucose tolerance of insulin secretion. This finding was supported by Notelovitz et al., who found no significant difference in lipid metabolism in active women using triphasic OCPs containing levonorgestrel and northinedrone at varying quantities in a prospective, controlled, 12-month trial. In addition, Suh et al., in an RCT, studied eight moderately active women using the same triphasic OCP formulation as Jacobs et al. and Casazza et al. (EE 0.035mg + norgestimate 0.18/0.215/0.250mg) and found no significant differences in RER or substrate utilisation during exercise. However, they did report a significant decrease (11%) in glucose appearance and disappearance rate, suggesting that the OCPs decreased glucose flux during moderate intensity exercise, rather than carbohydrate or lipid oxidation.
2.3.3 Overall Effect of OCPs on Metabolism
The differences in findings in the studies discussed may be due to the varying progestogens and doses in the OCP altering substrate utilisation. Indeed, OCP formulations containing norgestimate, norethindrone or desogestrel, and estrogen have eliminated the adverse effect of OCP use on carbohydrate and lipid metabolism.[45,52] As such, it may be those OCPs containing concentrations of norgestimate or desogestrel, and estrogen that would be beneficial to athletes as they would ensure stable physiological responses across the pill cycle. However, OCPs containing norlestrin and some quantities of norgestimate (table I and table II) may have some sparing effects on muscle glycogen, which is important in long duration sporting events (e.g. marathon running and football matches), as muscle glycogen is the only fuel utilised in high intensity work. The fuel would be required during high intensity bouts, occurring at various points throughout the event for tactical reasons or for winning certain challenges, as well as towards the end of the event when the athlete is fatiguing. As muscle glycogen has limited stores within the body, any sparing of the fuel throughout the event would be beneficial for the athlete at these crucial times. In addition, the variability in results to date could be due to the status of the women prior to exercise. Campbell et al. reported that in endurance-trained women, glycogen sparing and increased lipid oxidation only occurred when glycogen levels were initially low, highlighting the importance of adequate carbohydrates prior to exercise in women. However, this study was limited because the levels of glycogen were not measured directly, so the results should be taken with caution until further RCTs are undertaken.
2.4 Aerobic Capacity
2.4.1 Monophasic Oral Contraceptive Effects
In untrained women, it has been suggested that there is a decrease in peak oxygen uptake (V-dotO2peak) in conjunction with a significant reduction in mitochondrial citrate and a significant increase in oxygen consumption for standardised workloads when using monophasic OCPs. Such ventilatory changes have been suggested to be similar to that seen in the luteal phase of the menstrual cycle, whilst in highly trained women, it has been suggested that there are no significant effects of OCPs on aerobic capacity. However, many of these studies are cross-sectional in nature and were not carried out with the OCPs currently in use today (i.e. low dose triphasic or monophasic formulations).
When looking at the studies utilising the newer, low dose monophasic OCPs and more sophisticated study designs, the evidence suggests that there is no effect of monophasic OCPs on aerobic capacity in untrained women. Lynch and Nimmo assessed monophasic OCP formulations containing levonorgestrel 0.15mg or northisterone 0.50mg in untrained women and found no significant difference in V-dotO2peak between days 5–8 and 19–21 of the pill cycle. Such findings have been supported by Ruzic et al., who assessed 50 recreationally active students on a monophasic OCP containing levonorgestrel 0.15mg and found no significant differences in V-dotO2peak across OCP cycles. However, the findings for active/trained women are not as clear.
Notelovitz et al. examined the effect of long-term (6 months) administration of a monophasic OCP (EE 0.035mg + norethindrone 0.4mg) in active women and found a 7–8% decrease in V-dotO2peak in the OCP users, while the control group had increased V-dotO2peak over the same time period. Giacomoni and Falgairette stated that one may expect lower V-dotO2peak, but enhanced running economy during pill-ingestion phases in active women in the short term (one pill cycle) [EE 0.035mg + desogestrel 0.150mg or gestodene 0.075mg]. However, Lynch and Nimmo assessed monophasic OCPs in active women (EE 0.030–0.035mg + norgestimate 0.150mg or 0.250mg) and found no significant difference for aerobic performance or V-dotO2peak for either 1 or 2 weeks of monophasic OCP use. This could be due to the different progestogens utilised and their associated progestational and androgenic activity (table I), or the fact that different progestogens take different lengths of time to exert their effect on aerobic capacity. However, the fact that monophasic formulations regulate the hormonal milieu to a steady state, decreasing hormonal fluctuations across the cycle, one would hypothesise that they could provide a controlled environment for an athlete and minimise any potential variations in physiological variables. Further research is necessary to elucidate the exact effects of the various monophasic OCPs on aerobic capacity.
2.4.2 Triphasic Oral Contraceptive Effects
There is a growing body of evidence in support of the notion that aerobic capacity is impaired by triphasic OCP use as a result of the blunting of the sympathetic nervous system by the high ovarian hormone concentrations of OCPs. Many triphasic OCP studies have reported a decrease in V-dotO2peak post ovulation compared with pre ovulation. Lebrun et al. conducted a prospective, randomised, double-blind study involving 14 trained athletes over two pill cycles, using a triphasic OCP containing EE 0.035mg + northinedrone 0.5mg/1.0mg/0.5mg and found a 4.7% decrease in V-dotO2peak, even after adjusting for body mass. There were no changes in endurance performance, haemoglobin levels, maximum heart rate, RER or ventilation to account for this effect, thereby suggesting some other cellular mechanisms may be in operation. When looking at the effect of triphasic OCPs over longer periods of time, the findings are similar. Suh et al. and Jacobs et al., both using a triphasic formulation of norgestimate 0.18mg/0.215mg/0.250mg, studied aerobic capacity over four and six OCP cycles, respectively, and found decreases in the range of 11–15% in V-dotO2peak, but no effect on ventilation in active women. Casazza et al., using the same OCP formulation in active women, also reported a significant decrease in V-dotO2peak in the order of 11% and carbon dioxide release by 15%, with no significant differences in maximal heart rate, ventilation of RER, over 4 months of OCP use. To date, there has been no research into the effect of triphasic OCPs on aerobic capacity in untrained women.
2.4.3 Overall Effect of OCPs on Aerobic Capacity
It seems that the effects of OCPs on aerobic capacity are more pronounced in triphasic OCP formulations than in monophasic OCP formulations. As such, athletes may be advised to use monophasic OCP formulations instead of triphasic OCP formulations in events where aerobic capacity is important. However, the total effect of hormones on performance is a combination of endogenous and exogenous hormones. The exogenous hormones will suppress the endogenous hormones, but the level of exogenous hormones can not be easily measured and thus results need to be viewed with caution.
2.5 Cardiovascular Responses
2.5.1 Monophasic Oral Contraceptive Effects
It has been postulated that the estrogen-induced increase in plasma volume by OCP administration could have a beneficial effect on performance by increasing preload and cardiac output. However, some studies have found no significant alterations in cardiac index, pulmonary artery distensibility, heart rate or blood pressure in inactive women on a variety of monophasic OCPs.[56,57] In contrast, Lehtovirta et al. have shown a higher cardiac output during exercise, as well as increases in plasma volume and stroke volume in inactive women on monophasic OCPs. Walters and Lim measured an increase in systolic blood pressure and cardiac output after 2–3 months administration of a monophasic OCP in inactive women, without any associated increase in heart rate. A higher cardiac output and blood volume could theoretically result in increased oxygen delivery to the tissues and is likely to be secondary to an increase in vascular volume, mediated through a hormonally induced increase in aldosterone secretion. However, these studies utilised the old generations of OCPs containing high levels of estrogen, which are now generally not in use.
Although there is not an abundance of research on the newer monophasic OCPs, those studies that have been completed are well controlled and designed. Lynch and Nimmo assessed active women using a new, low dose monophasic OCPs (EE 0.030–0.035mg + levonorgestrel 0.150mg or norgestimate 0.250mg) and reported no significant differences in heart rate responses between days 2–8 and 9–15 of the pill cycles. In 2001, the same authors reported identical findings in a group of untrained women using similar monophasic OCPs. Coney et al. studied 349 monophasic OCP users (EE 0.020mg + levonorgestrel 0.100mg) over 6 months of pill use and reported small, but significant increases in systolic blood pressure (1.05mm Hg), but no changes in diastolic blood pressure in untrained women. Tantbirojn and Taneepanichskul studied inactive women using monophasic OCPs and reported no significant difference in blood pressure between controls and the OCP groups. Thus, it appears there is no significant performance effect of monophasic OCPs on these cardiovascular responses to exercise.
2.5.2 Triphasic Oral Contraceptive Effects
The research on cardiovascular responses and triphasic OCP use is sparse, but those studies which have been completed are RCTs and, thus, offer valuable insights into the area. Casazza et al. assessed eight active women on a triphasic formulation of EE 0.035mg and norgestimate 0.18mg/0.215mg/0.250mg, and found that over one to four cycles of OCP use, there was no effect of the OCP on maximal heart rate. Such a finding was supported by Suh et al., who assessed eight active women using an identical triphasic OCP and reported no significant differences in heart rate or blood pressure across four pill cycles. Lastly, Lebrun et al. assessed trained women using a different triphasic OCP formulation of EE 0.035mg and northinedrone 0.5mg/1.0mg/0.5mg, and still reported no significant changes in maximal heart rate across two cycles of OCP use.
2.5.3 Overall Effect of OCPs on Cardiovascular Responses
Overall, it appears that although the research in this area is sparse, the well controlled studies that have been completed indicate that there are no significant effects of monophasic or triphasic OCP formulations on cardiovascular responses at rest or during exercise. Thus, the choice of OCP formulations is open to the athlete.
2.6 Anaerobic Capacity
It has been hypothesised that anaerobic performance would be altered in cyclic patterns throughout an OCP cycle, with the best performances observed when the levels of exogenous hormones administration were low (days 21–28), with such levels of sex steroids facilitating carbohydrate metabolism and improving buffering capacity. However, there is no consensus in the literature as to whether anaerobic performance is affected by the synthetic menstrual cycle of the OCP user.
2.6.1 Monophasic Oral Contraceptive Effects
In active women with administered monophasic OCPs, no significant difference in performance time or lactate accumulation has been found. This was replicated by Lynch and Nimmo in untrained, monophasic OCP users, where no significant differences in performance time over 20-second sprints or lactate accrued during the maximal test were found. In addition, De Bruyn-Prevost et al. found no significant difference in lactate levels or absolute strength across one pill cycle in seven untrained OCP users (OCP not reported). As monophasic pills do not fluctuate hormone levels, they seem to provide a controlled environment for an athlete and, therefore, may not affect strength performance to the same extent as triphasic OCPs.
2.6.2 Triphasic Oral Contraceptive Effects
Redman and Weatherby suggest that competitive rowers using a triphasic OCP show an increase in peak power and 1000-metre row time during days 26–28 of the pill cycle when estrogen and progestogen concentrations were low. Not only was anaerobic power and capacity improved at this time, but a 3-second improvement in the 1000-metre row time trial was reported. Therefore, given that some women are already using OCP to control menstrual bleeding, the OCP could also be utilised to ensure the hormonal milieu on the day of competition would foster an improvement in performance. Such improvements could be the result of secondary cellular effects of estrogen and progestogen equivalents on substrate utilisation and buffering capacity. Improved buffering capacity, thought to be a determinant of muscular fatigue, could enhance anaerobic capabilities during the late luteal phase and early follicular phase, and at the placebo stage of the triphasic OCP administration. Lebrun et al. conducted another study into triphasic OCPs and anaerobic capacity in trained women (EE 0.035mg + northinedrone 0.5mg/1.0mg/0.5mg) and found no significant differences in anaerobic performance, as judged by an anaerobic speed test, in the OCP users across two pill cycles. Such findings are similar for active women over a longer period of time, with Suh et al. reporting no significant differences in blood lactate responses during exercise at 45% and 65% V-dotO2peak, over four cycles (EE 0.035mg + norgestimate 0.18mg/0.215mg/0.25mg). However, Casazza et al. conducted another 4-month trial using the same triphasic formulation (EE 0.035mg + norgestimate 0.18mg/0.215mg/0.25mg) and found that after 4 months of OCP use, there was a significant decrease in peak power output (8%) and peak exercise capacity. Thus, the effects of the triphasic OCP may differ depending on the anaerobic variable measured, the intensity of the anaerobic exercise performed and the length of time the athlete has been taking the OCP formulation.
2.6.3 Overall Effect of OCPs on Anaerobic Capacity
The lack of significant difference found on anaerobic performance relating to OCPs could be due to the short duration of activity. The sex steroids exert their effect mainly on lipid and glycogen utilization, and it is this effect on substrate utilisation that is hypothesised to affect performance. Adenosine triphosphate and phosphocreatine are the main supplies of energy in short duration events, such as short-term anaerobic performance and strength. Estrogen and progestogen in such events will only have limited effect as glycogen and lipids are not utilised. In addition, the total effect of hormones on performance is a combination of endogenous and exogenous hormones. The exogenous hormones will suppress the endogenous hormones, but the level of exogenous hormones cannot be easily measured and, thus, results need to be viewed with caution. Therefore, the choice of OCP formulations is open to the athlete.
2.7 Muscle Strength
There have been few studies on the effects of OCP administration on muscle strength and the studies so far suffer from problems of design and small sample size. In terms of muscle strength, extrapolation from the known effects of anabolic steroids might suggest that androgenic components of OCPs could have some positive effects on strength. However, this is as a result of the findings that postmenopausal women on hormone replacement therapy during the menopause exhibit maximum voluntary forces and greater muscle cross-sectional area compared with age-matched controls, and similar to that of young women.The research into OCPs and the effect on strength is less than that of aerobic or anaerobic performance. In addition, estrogen has been researched to a greater extent than progestogen in terms of strength performance.
2.7.1 Monophasic Oral Contraceptive Effects
To date, the studies in this area show lower static handgrip strength endurance and no change in forearm maximal voluntary contraction (MVC) in inactive, OCP users compared with controls. Petrofsky et al. tested seven inactive women on a variety of OCPs and found no significant difference in static muscle strength in OCP users compared with controls. In fact, the controls experienced a decrease in forearm isometric endurance at 40% MVC during the luteal phase. Thus, the authors postulated that this decrease was due to an increase in deep muscle temperature in the control group that was not present in the OCP users. However, the study design and small sample size make these results difficult to interpret. As a result of the new, low-dose monophasic oral contraceptives providing the participant with a constant estrogen level, the fluctuation related increase in strength should not occur. Indeed, Elliot et al. studied 14 monophasic OCP users and found there was no significant difference in maximal force production of the dorsal interosseus muscle pre and post ovulation over a range of OCPs used. Ruzic et al. supported such findings in 26 sedentary OCP users participating in 16 weeks of strength training. However, Phillips et al. found a significant increase in maximal voluntary force by 10% of the adductor pollics muscle over 6 months in trained and untrained OCP users and controls, but the OCP formulation was not specified and, thus, the results are difficult to interpret.
2.7.2 Triphasic Oral Contraceptives Effects
One of the few prospective studies on isokinetic strength and oral contraceptives was conducted by Lebrun et al. on 14 trained women using triphasic OCPs (EE 0.035mg + northinedrone 0.5mg/1.0mg/0.5mg). No significant difference was found over two pill cycles in peak isokinetic strength measures.
2.7.3 Overall Effect of OCPs on Strength
It is the progestogen prescribed in the contraceptive that determines the effect of the estrogen.[9,10] The progestogen content of the OCP varies in potency and androgenocity and, therefore, the effect on estrogen also varies. However, it seems that OCP formulations do not provide a large enough androgenic component to influence strength, with the two most notable androgenic progestogens, levonorgestrel and norethindrone, also having anti-androgenic properties; therefore, the choice of OCP formulations is open to the athlete. However, more long-term controlled trials on the various OCP formulations and strengths are required before firm conclusions can be made.
Research has also focused on OCPs and the effect on muscle soreness and recovery; however, the research is very sparse and the OCP type and formulations used unclear. Thompson et al. found that there was no difference between active OCP users and eumenorrheic women with respect to muscle damage, but that OCP users perceived less muscle soreness following exercise. This led to the conclusion that OCP users may have a higher pain threshold due to the exogenous progestogen and estrogen, and this may influence the maximal force they can produce. This was disputed by Savage and Clarkson, who found that student OCP users had longer recovery periods following maximal strength testing and had no significant difference in soreness perception compared with controls. However, the OCP formulations were not reported in these studies and, thus, the results should be viewed with caution. Until further trials are conducted, the possibility that the various progestogens present in OCP preparations may affect recovery from exercise and training in women should remain.
Investigators are not in agreement as to the effects of OCP administration on many of the physiological factors related to performance. It is a complicated area due to the proliferation of OCP formulations currently on the market. Current OCP formulations contain less hormones and this can be expected to have less of a physiological impact on athletic performance than the older formulations used in earlier studies. However, investigators are not in agreement on either the quantitative or directional effects of OCP use on physiological variables and performance. Most of the inconsistencies between studies are likely to be the result of: (i) varied methods for determining choice of testing days through the OCP cycle; (ii) type of OCP utilised resulting in variations in potency and androgenicity of formulations; (iii) small sample sizes; and (iv) assessing women over a limited number of pill cycles. Further studies are required into the effects of monophasic and triphasic formulations, and their effects on athletic performance. These need to be appropriately randomised and controlled trials. Whatever the results of such trials, it is likely that there will be a large inter-individual variability in response to exogenous steroid hormones contained within OCPs. As such, it is prudent for a female athlete who is considering taking an OCP to consider, along with her general practitioner and coach, the formulation of the OCP and its potential effect on health and specific performance variables. An athlete should try as many formulations as it takes to find the ‘right’ OCP for her amongst the many that are currently on the market. The type of OCP (monophasic or triphasic), as well as the potency and androgenocity of the progestogen, may determine the OCP’s potential effect on performance and should therefore be considered.
4. Future Research
There is a need for more research to assess the effect of OCPs on the physiological variables of performance and the mechanisms behind any such effects that may be observed. To date, the majority of the studies have reported the effects of OCPs on body composition, metabolism, substrate utilisation and aerobic capacity, leaving a dearth of research into core body temperature, cardiovascular responses to exercise, anaerobic capacity, strength and recovery. All of these variables impact on female athletic performance and, thus, need to be examined with respect to the OCP. However, to conduct well controlled studies into this area, the following important issues need to be considered: (i) the trained status of participants; (ii) the sample size; (iii) the type of OCP to test; (iv) which days to test throughout the OCP cycle; (v) the number of OCP cycles to test; and (vi) the interpretation of data with respect to statistical and meaningful differences.
Future studies need to assess the effects of OCPs on performance across a variety of trained levels because the effects of the OCP on performance may be different in inactive, moderately active, trained and elite individuals. In addition, the resulting effects on performance may be more important in the elite athlete compared with the moderately active woman. As such, studies should ensure that participants are of a similar trained status and that study findings may not be generalisable to other women. Numerous studies have been conducted on small sample sizes, using cross-sectional designs with no randomisation and, as such, these results need to be viewed with caution. Future studies need to ensure that they are randomised appropriately for the study design and that they retain adequate power when assessing the effect of OCPs on performance in order to accurately report the OCP effects. Although such trials are arduous and costly, it is the only way to ensure reliable results.
The varying amounts of OCP formulations available today have resulted in much of the literature confusion regarding OCPs and performance. Future studies need to investigate one type of OCP formulation at a time, taking into consideration the exact type and amount of EE and progestogen within the OCP and, thus, its potency and androgenicity. Only then will this clarify the exact effect of varying OCP formulations on performance and allow comparisons between OCPs of varying potency and androgenicity. Regarding the type of OCP to test, future studies need to concentrate on the myriad of monophasic and triphasic OCPs now available. It is also important to test across these formulations, allowing for a wide range of information to be available to athletes and support staff so their decisions regarding which OCP to choose are founded on evidence.
The days of the OCP cycle on which to test are imperative to allow a clear picture of the effects of OCPs on performance. Looking at figure 2, one can see that monophasic OCPs have high EE and progestogen until day 21, at which time the hormones decrease due to 7 days of placebo pills being introduced. Thus, it would make sense to test during the high EE and progestogen doses, compared with the low EE and progestogen doses. With regard to triphasic OCPs, one would need to test during the ranges of days 2–8, 8–12, 12–21 and 22–28 to cover the varying doses of hormones (figure 2). Where possible, there should be 2–3 test days during each hormone level to ensure that any effects seen are consistent across the time span. For the monophasic OCP, there is time to achieve this; however, for the triphasic OCP this may prove difficult and, thus, would warrant additional OCP cycles to be tested to achieve the required two to three tests during each hormonal level. In conjunction with the testing days, one should take into consideration how long the woman has been using the OCP and test over a number of OCP cycles to ensure that any short-term effects are also long-term effects and vice-versa. Therefore, we suggest that at least six pill cycles should be tested.
Lastly, when interpreting data one needs to keep in mind that non-significant changes may be meaningful in an athletic context, particularly with regards to highly trained/elite female athletes. For example, a small change in body mass (1kg) may not be significant but would be meaningful to a female marathon runner who has to carry the extra body mass over 42.2km.
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No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.