Introduction

Intracranial hemorrhage (ICH) is a rare, yet recognized cause of sudden death during and shortly after sexual activity [22, 30]. The majority of reported cases involve aneurysm rupture with subsequent subarachnoid hemorrhage (SAH) [7, 22, 29, 30, 34]. Hypothesized pathophysiologic mechanisms emphasize changes in transmural pressure across the aneurysm dome coincident with the physiologic changes that accompany the stages of the human sexual response [36]. While the role of sexual activity in aneurysm rupture has been explored, there is a paucity of data on sexual activity’s role in other forms of ICH.

Sexual intercourse is known to produce a hyperdynamic circulatory state in both men and women, manifested by increased heart rate and blood pressure [24, 36]. Long-standing hypertension is an established risk factor for hemorrhagic stroke [9, 18], and illicit drugs known to produce acute blood pressure elevations have also been identified as risk factors [35, 43]. Thus, the hyperdynamic circulatory state experienced during sexual activity has the potential to increase the risk of not only aneurysmal SAH, but ICH of all types.

A case-series of patients with ICH following sexual activity is presented to describe the clinical characteristics, raise awareness of this condition, and further elucidate the role of the physiologic sexual response as a trigger of ICH.

Methods

A retrospective review of the medical record was performed to identify patients presenting with non-traumatic ICH of any etiology related to sexual activity from 2007 to 2014 at Beth Israel Deaconess Medical Center (BIDMC). This protocol was approved by the Institutional Review Board.

All adult patients presenting with non-traumatic ICH, diagnosed by history and computed tomography (CT) or magnetic resonance imaging (MRI), were eligible for inclusion. Aneurysmal SAH is defined as non-traumatic SAH in the setting of an intradural aneurysm. Angiogram-negative SAH includes all non-traumatic cases of SAH where a diagnostic cerebral angiogram failed to identify a vascular malformation. Arteriovenous malformation (AVM)-related hemorrhages were defined as any hemorrhage that could be spatially attributed to an identified AVM. Intracerebral hemorrhages (ICHs) were defined as hemorrhages occurring within the brain parenchyma that could not be attributed to a vascular lesion—classically known as “hypertensive hemorrhages”. Admission notes were reviewed with particular attention to events preceding the onset of symptoms. If a history of sexual activity, including masturbation, was identified during or within 2 h of symptom onset, the ICH was deemed temporally related to sexual activity and the patient was included as a study subject.

Demographic information, including age, sex, history of hypertension, current use of illicit drugs, current use of antithrombotics and/or phosphodiestersase-5 (PDE-5) inhibitors, type of sexual activity preceding symptoms, presenting signs and symptoms, and diagnostic work-up, was recorded. Radiographic data, including initial non-invasive imaging and angiography results, were recorded. Data on therapeutic intervention were noted when performed.

Results

Sixteen patients were identified as presenting with non-traumatic ICH temporally related to sexual activity. Overall average age was 49.9 (range, 28–74) years, 13 (81.3 %) were male, and history of hypertension was present in 5 (31.3 %) patients. Two (12.5 %) patients were taking oral PDE-5 inhibitors, one (6.3 %) patient was taking aspirin, and one (6.3 %) was abusing cocaine. Presenting symptoms included headache in 13 (81.3 %) patients and seizure in 4 (25 %). Presenting exam included a new focal neurologic deficit in four (25 %) patients (Tables 1 and 2).

Table 1 Aneurysmal hemorrhages
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Table 2 Non-aneurysm-related hemorrhages
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Eight (50 %) patients presented with aneurysmal SAH with an average age of 43 years. Seven out of these eight (87.5 %) were men. Four (25 %) patients presented with angiogram-negative SAH with an average age was 58 years; all were men. Two (12.5 %) patients presented with a ruptured AVM with an average age of 54 years; one was male. Two (12.5 %) patients presented with an intracerebral basal ganglia hemorrhage with an average age of 54 years; one was male.

Sexual activity involved male–female intercourse in 14 (87.5 %) patients and masturbation in 2 (12.5 %) patients.

Discussion

Sexual activity induces a hyperdynamic circulatory state that is hypothesized to predispose at-risk patients to non-traumatic ICH primarily through elevations in arterial blood pressure. This sex-induced hyperdynamic physiologic state is supported by reports of iliac aneurysm rupture [20], aortic dissection [15, 28], and aortic aneurysm rupture [12]. While the pathophysiologic mechanisms of sex-induced intracranial aneurysm rupture are defined [36], little is known about the role of sexual activity in other forms of hemorrhagic stroke.

Aneurysmal SAH

Sexual activity is a recognized risk factor for intracranial aneurysm rupture [5, 40, 42]. The interplay between the physiologic sexual response and aneurysm rupture was eloquently stated by Reynolds et al. [36] In short, as humans enter the late plateau and orgasmic phases of the sexual response cycle, elevated muscle tone and mean arterial pressure (MAP) occur concomitantly with hyperventilation-induced decreases in intracranial pressure (ICP) [36]. This results in an increased cerebral perfusion pressure (CPP), thus an increased transmural pressure gradient across the aneurysm dome that predisposes to aneurysm rupture [36].

Interestingly, seven of the eight cases of aneurysmal SAH occurred in males. Despite the overall female predominance in aneurysmal SAH [25], the male-to-female ratio of aneurysmal SAH during coitus is less clear. A possible explanation for the unexpected male predominance centers on a greater overall increase in MAP during intercourse [24, 36]. Patients presenting with sexual-activity-related aneurysmal SAH also tended to be younger with an average age of 43 years, compared with 54 years reported in a large contemporary aneurysmal SAH trial [25]. The cause of this discrepancy is not known, and could simply represent sampling error due to small numbers.

ICH of other etiologies

Angiogram-negative SAH is an all-encompassing term that includes non-aneurysmal SAH and perimesencephalic SAH and is used in this study to indicate the absence of a vascular lesion in the setting of non-traumatic SAH. While venous anomalies are theorized as the source of SAH, the etiology of these hemorrhages is not known [19]. However, evidence suggests that non-aneurysmal perimesecephalic hemorrhages are more commonly associated with straining at the time of ictus than aneurysmal SAH [3, 19, 44], potentially explaining its occurrence during sexual activity.

The Valsalva maneuver has been implicated as a trigger for aneurysm rupture [38], non-aneurysmal perimesencephalic hemorrhage [44], and venous cerebral hemorrhage [2]. The maneuver increases intrathoracic pressure, which in turn decreases venous return to the heart leading to transient cerebral venous hypertension and elevated intracranial pressure [17, 33]. Transmission of intrathoracic pressure to cerebral venous circulation is hypothesized to underlie venous cerebral hemorrhage in some cases, particularly in the presence of jugular valve incompetence [1, 2]. While a similar mechanism is proposed for non-aneurysmal perimesencephalic hemorrhage [44], aneurysm rupture is likely precipitated at the end of the maneuver when elevated arterial blood pressure is met with a drop in venous and intracranial cerebrospinal fluid pressure, leading to increased transmural pressure across the aneurysm dome [36, 38].

Hypertension is an established risk factor for ICH [9]. Physical activity, including sexual intercourse, has been identified as a potential external trigger for ICH with an increase in blood pressure as the major contributing factor [32]. The role of physical activity as a trigger for ICH is further supported by the marked reduction in the incidence of ICH at night, when people are usually sleeping [31]. Mean arterial blood pressures during intercourse are estimated at 130–175 mm Hg in men and 125–160 mm Hg in women [36]. These values are nearly double normal MAPs and have the potential to outstrip cerebral autoregulation [36], increasing the risk of hemorrhage. Hypertension has also been identified as a risk factor for AVM rupture [21]. Extrapolation of the hypertensive risk of sexual activity to the rupture of brain AVMs appears reasonable.

Oral phosphodiesterase-5 inhibitors are commonly used for the treatment of erectile dysfunction (ED). Since the approval of these medications in 1998, several reports have tied their use to ICH [4, 8, 11, 23, 26, 37, 39]. Interestingly, not all adult cases were associated with sexual activity [26] and one case occurred in an infant being treated for pulmonary hypertension [37]. Two (12.5 %) patients in the current series reported use of oral PDE-5 inhibitors and both were associated with sexual activity. While PDE-5 inhibitors do not carry a warning specific to ICH, animal model and ex vivo data suggest that PDE-5 inhibitors can inhibit platelet aggregation [6, 10, 41]. Other side effects, including headache and flushing [16, 27], indicate that the vascular effects may not be limited to the corpus cavernosum of the penis. Further investigation is needed to determine the effect of PDE-5 inhibitors on ICH; it remains a potential contributor to the male predominance in the current series.

The role of sexual activity as a cause for ICH, other than aneurysmal SAH, is poorly defined. The body of literature on the topic is little more than a handful of case reports and small series [2, 13, 14, 32, 39]. While these reports bring attention to the topic, the small number of patients makes meaningful discussion and conclusion challenging. It is likely that the rarity of sexual-activity-related ICH is such that it will require multicenter collaboration. The current study combined nearly a decade worth of patients from a high-volume stroke center to present the largest series on the topic. Underreporting is another challenge associated with what might be regarded by patients as an embarrassing or taboo subject.

Recommendations

Given the lack of available data, evidence-based guidelines on sexual activity as it relates to ICH are not feasible. While appropriate primary and secondary prevention strategies are uncertain, it seems intuitive to avoid the use of PDE-5 inhibitors if they were implicated in the initial hemorrhage. For hemorrhages related to underlying etiologies that have been successfully treated, it seems reasonable for patients to resume sexual activity. In the case of spontaneous hemorrhages, there are no data to support the recommendation of indefinite abstinence.

With regard to the workup for patients presenting with coital headache, formal recommendations cannot be made due to a paucity of data. In cases presenting with focal neurologic deficits or altered level of consciousness, cranial imaging is reasonable. For cases presenting with only a headache, the physician’s clinical acumen should guide the diagnostic workup.

Limitations

Data collection was performed in a retrospective fashion. This limits the available data to those items routinely collected on admission and during the hospital stay. There is a significant risk of underreporting. Patients present in a stressful situation and are subject to recall bias. Additionally, the sensitive nature of a sexual history may limit voluntary reporting and physician inquisition. It is possible that a gender difference exists in the reporting of sexual activity, another potential explanation for the male predominance in this series. Small numbers of study subjects limit analysis and conclusion; this is inherent to rare diseases, or in this case, rare circumstances in which disease occurs.

Conclusions

Sexual-activity-related ICH is rare and includes aneurysmal SAH, angiogram-negative SAH, AVM rupture, and intracerebral hemorrhage. The human sexual response is associated with dramatic increases in arterial blood pressure. This acutely induced state of hypertension is likely responsible for sexual-activity-induced ICH.