Hormonal Contraceptives and Travel to High Altitude

Types of Hormonal Contraception

Hormonal contraception is available as oral contraceptive pills (OC), injectable and implantable forms, a hormonal patch or vaginal ring, and via intrauterine device (IUD). OCs come in various formulations of combined estrogen and progestin or progestin only. Detailed discussion about individual formulations is beyond the scope of this review. Table 1 lists the major types of HC, efficacy, and risks and benefits related to high altitude travel with condoms as a comparison.

Control of Menstruation

The stresses of travel and high altitude may disrupt the normal pattern of menses. Women report changes in the timing and quantity of bleeding, as well as missed periods during high altitude sojourns (Miller, 1999). Menstrual irregularity has also been observed in space travel (Jennings and Baker, 2000) and in flight attendants (Radowicka et al., 2013), though this is thought to be primarily due to chrono-biological disruptions or other stresses, and not hypoxia per se.

Besides preventing pregnancy, an additional benefit of HC is the ability to control the timing of menses and thereby avoid uncertainty about pregnancy versus travel-related changes to the normal cycle. Furthermore, for convenience and hygiene, mountaineers and those traveling in remote environments may wish to suppress menstrual bleeding. Combined OCs are safe and effective for this purpose without altering their contraceptive efficacy (Anderson and Hait, 2003), and many women report doing this on high altitude treks (Miller, 1999). There are no risks associated with delaying or suppressing menstrual bleeding for up to one year (Wright and Johnson, 2008). In women taking traditional OCs, menstrual suppression is achieved by skipping the placebo pills or “off week”, and instead starting the next pill pack. Some combination pill formulations are specifically designed for continuous use for up to 3 months (Seasonale ^® , Seasonique ^® ) or 1 year (Lybrel ^® ) without withdrawal bleeding. A woman wishing to suppress menstrual bleeding with OCs should start a few months in advance of planned travel, as breakthrough bleeding may occur in the first few cycles of use (Wright and Johnson, 2008).

Likewise, injectable HC, implantable HC, and hormone-releasing patches, rings, and IUDs also eliminate monthly bleeding. These methods, however, may be associated with spotting or unscheduled bleeding. With IUDs, most bleeding occurs in the first 3 months of use and within the first year with implants (Centers fo Disease Control and Prevention, 2013). Nonsteroidal anti-inflammatory drugs (NSAIDs) may be effective to stop breakthrough bleeding (Centers fo Disease Control and Prevention, 2013). A woman wishing to suppress menses with these types of HC should begin well in advance of travel to learn how her body will respond and carry a supply of NSAIDs.

Acclimatization and Exercise Performance

In theory, hormonal changes related to the menstrual cycle or HC could affect acclimatization to high altitude. Progesterone is a well-known respiratory stimulant (Skatrud et al., 1978) and also has beneficial effects on respiratory musculature (Brenner et al., 2005). Nonetheless, most studies have shown no influence of the menstrual cycle on short-term adaptation to high altitude, including exercise performance (Mazzeo et al., 2001, Takase et al., 2002), or cardiovascular function. (Mazzeo et al., 1998). Nor have HCs been shown to influence exercise performance at high altitude (Sandoval et al., 2001, Sandoval and Matt, 2003).

Sandoval and colleagues compared ventilatory and catecholamine responses to exercise in hypoxia in eight women on OCs in the hormonal versus the placebo phase of the pill cycle (Sandoval and Matt, 2003). Intriguingly, in this small study, lactate was lower and glucose was higher during the recovery phase of hypoxic (but not normoxic) exercise during the hormonal phase of OCs, suggesting that women may have better endurance for hypoxic exercise during the hormonal phase of their pill cycle. This could be a theoretical advantage to HC for women performing endurance activities at high altitude, but this observation has not yet been confirmed in other studies.

Acute Mountain Sickness (AMS)

The incidence of AMS does not differ by gender (Hackett and Roach, 2001; Bartsch and Swenson, 2013) and the phase of the menstrual cycle does not influence the incidence of AMS in women (Rock, 2001). However, healthy pre-menopausal women have fewer apneic-hypopneic events during sleep than healthy men at high altitude (Caravita et al., 2014). Some authors have argued that because HC suppresses ovulation and thereby prevents progesterone secretion from the corpus luteum, theoretically, progesterone suppression could be a detriment to respiratory acclimatization, and might increase the risk of sleep disturbance or altitude illness (Wright et al., 2004). On the other hand, taking synthetic progesterone in the form of HC could have beneficial effects due to its respiratory stimulatory properties (Skatrud et al., 1978). Evidence is conflicting for which theory is correct.

Sandoval et al. (2001) found that in seven women on OCs, the incidence of AMS after 9 hours at simulated altitude of 4572 m was lower than expected, lower than in men who underwent a similar protocol, and was not increased with exercise as it was in men. These results support the idea that the respiratory stimulating effects of exogenous progesterone are beneficial at high altitude. The small number of participants and the relatively short altitude exposure, however, limit the ability to draw firm conclusions from this study.

On the other hand, in a study of predominantly men at 4680 m and 5200 m, supplemental medroxyprogesterone did not prevent AMS and had no effect on end-tidal CO₂ or peripheral oxygen saturation compared to placebo or acetazolamide (Wright et al., 2004). Furthermore, a recent study of fifty women traveling rapidly to the physiologic equivalent of 3800 m in Antarctica found a higher incidence of AMS in women taking OCs compared to those who were not (Harrison et al., 2013). These authors also found that acetazolamide did not prevent AMS in women taking OCs, whereas it did prevent AMS in half of the women who were not (Harrison et al., 2013) The observational design (nonrandomized) and the relatively small number of subjects on OCs (n=13) limit broad clinical application of these surprising findings. Nonetheless, the results are of potential concern to women on OCs wishing to use acetazolamide for prevention of AMS and require verification. It is unknown whether other forms of HC may also increase or decrease the risk of AMS.

Thrombosis

A primary concern for women taking HC at high altitude has been the associated risk of thromboembolic disease. Although the risk of thrombosis is increased in women on OC compared to women not taking OC, the absolute risk remains lower than the risk of venothromboembolism (VTE) in pregnancy (ACOG Committee on Practice Bulletins-Gynecology, 2006; reaffirmed, 2013). In smokers, the risk of arterial clots (i.e., myocardial infarction and stroke) is increased with OC, particularly in women older than 35 years (ACOG Committee on Practice Bulletins-Gynecology, 2006; reaffirmed, 2013; Centers fo Disease Control and Prevention, 2013). Depot injected forms of HC are also associated with an absolute increase in thrombotic risk, but progestin-secreting IUDs are not (van Hylckama Vlieg et al., 2010) and progestin-only pills have a lower risk of thrombosis than forms of combined OC (ACOG Committee on Practice Bulletins-Gynecology, 2006; reaffirmed, 2013). Combined OC and the hormonal patch and ring are not recommended for women who smoke and are over age 35 years, have known clotting disorders, or a history of VTE, whether or not they are traveling to high altitude (Centers fo Disease Control and Prevention, 2013).

It is unclear if the combination of high altitude and HC leads to an unacceptable risk of thrombosis in otherwise low-risk women. High altitude exposure alone may be an independent risk factor for thrombosis (Anand, 2001; Segler, 2001). Many case reports document thromboembolic events occurring at high altitude, but the mechanism and the role of hypobaric hypoxia in these events remains uncertain (reviewed in Gupta and Ashraf, 2012). No systematic data on the combined risk of altitude and HC exist. I am aware of one case of a nonsmoking woman taking OC who had a stroke while trekking above 4000 m with a negative hypercoagulability work-up (D. Shlim, MD, oral and written communication, 2010). A single published report documents cerebral venous sinus thrombosis in a woman taking OCs and working as an instructor in a hypobaric chamber (Torgovicky et al., 2005). The patient was a nonsmoker and had no other risk factors for hypercoagulation. The authors postulate that a combination of hypobaric hypoxia and OCs played a role in the development of clot in this patient (Torgovicky et al., 2005).

A prudent approach would be to advise women that OCs may pose a greater risk for thromboemobolism at high altitude than they do at sea level due the potential for multiple combined risk factors. These include dehydration, immobility in mountaineers who may be stranded in tents for long periods due to weather, cold effects on peripheral perfusion, hemo-concentration, thrombocytosis, and possibly other effects of hypoxia (Gupta and Ashraf, 2012).

Other Concerns with HC

OCs have some practical disadvantages when traveling. Pills need to be taken at the same time every day, which may be difficult when changing time zones and moving daily. Disruptions in the timing may lead to decreased efficacy and breakthrough bleeding. In the event of loss or separation from her belongings, a woman would be without her medication. Women are advised to carry a supply of back up pills (Hillebrandt, 2009).

The concomitant use of HC and antibiotics has been raised as a potential concern for travelers (Hillebrandt, 2009). A recent comprehensive review of this question concludes, however, that only rifampin substantially decreases hormone levels (ACOG Committee on Practice Bulletins-Gynecology, 2006; reaffirmed, 2013). Other antibiotics commonly used during travel such as quinolones, azithromycin, penicillins, tetracycline, and metronidazole do not lower steroid hormone levels or decrease the efficacy of OC (ACOG Committee on Practice Bulletins-Gynecology, 2006; reaffirmed, 2013).

Guidelines

The UIAA published two consensus statements that address the issue of contraception use at high altitude (Jean, 2008; Hillebrandt, 2009), and the issue of HC at high altitude is addressed in the British Faculty of Sexual and Reproductive Healthcare Clinical Guidance (Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit, 2011). The findings and conclusions of the present article are largely in line with the recommendations in these white papers. FSRH guidelines recommend that women traveling to altitudes over 4500 m for more than 1 week not use HC, but rather choose another form of contraception (Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit, 2011). The Guidelines provide no rationale for these cut-offs, though the caution may be due to the theoretical concern of thrombosis. Evidence to support these limits on altitude and time is lacking.

Conclusions

For women traveling to high altitude, HC has some potential risks and inconveniences, but in most women already using HC these risks are low, and probably do not outweigh the advantage of continuing their current form contraception. Any woman starting a new form of hormonal contraception should be encouraged to do so several months in advance of travel. More research is needed on the relationship between HC and AMS. For women starting a new form of contraception and for whom high altitude travel is a factor, I recommend progestin-secreting IUD as the first line form of contraception for its several advantages compared to other forms of HC (Table 1). The progestin-secreting IUD has a lower risk of thrombosis,(van Hylckama Vlieg et al., 2010) is more effective at preventing pregnancy, will suppress menses, and is safe in nulliparous women (Centers fo Disease Control and Prevention, 2013), with the caveat that condoms should be used to prevent sexually transmitted diseases.