Balancing Catamenial Pneumothorax Management with Fertility: Insights from GnRH Agonist Use

Introduction

Endometriosis is a chronic, non-malignant disorder characterized by abdominal pain during menstruation, driven by a combination of genetic, hormonal, and immunological factors that enhance endometrial cell invasion and angiogenesis impairment [1,2]. It affects approximately 5% to 15% of reproductive-aged women and, although primarily pelvic, it can manifest in extrapelvic locations such as the thoracic cavity [3]. Thoracic endometriosis (TE) is a rare but notable form, in which endometrial tissue grows in the pleura, lungs, diaphragm, or airways [3,4].

The most frequent clinical presentation of TE is catamenial pneumothorax (CP), a spontaneous lung collapse that occurs during or within 72 hours of menstruation onset [5]. CP is marked by chest pain and respiratory distress, and can coexist with pelvic endometriosis, infertility, or other thoracic symptoms like hemothorax or hemoptysis [5,6]. Due to its overlapping features with primary spontaneous pneumothorax and low awareness, CP often remains underdiagnosed or misdiagnosed [7,8].

Accurate diagnosis requires a high index of suspicion in women with recurrent pneumothorax and a history of endometriosis [9]. Diagnostic tools include chest imaging, video-assisted thoracoscopy (VATS), and histological confirmation through biopsy, with immunohistochemical markers like cytokeratin-7 and hormone receptors aiding detection [6]. Notable findings can include diaphragmatic fenestrations or pigmented lesions. Histopathology often reveals eosinophilic infiltration and macrophage dominance [9].

The management of CP primarily focuses on treating the pneumothorax and minimizing the risk of recurrence [10]. Hormonal therapy, often used to suppress ectopic endometrial activity, is a mainstay of treatment [11]. However, it poses significant challenges for women seeking to conceive, as it can interfere with ovulation and delay fertility plans [12]. The absence of standardized clinical guidelines for the management of CP in infertile women necessitates an individualized, multidisciplinary approach. This case report explores the management of catamenial pneumothorax (CP) in a woman desiring pregnancy. After receiving a gonadotropin-releasing hormone (GnRH) agonist for intrauterine insemination but no other hormonal therapy, she developed progressive CP over 10 years. This report shows the clinical complexity of CP in the context of infertility, illustrating the critical need to balance effective symptom control with strategies aimed at preserving reproductive potential. Unlike conventional treatment approaches that prioritize hormonal suppression, this case underscores the need for individualized strategies that balance CP control with fertility preservation.

Case Report

POSTOPERATIVE FOLLOW-UP:

The patient’s postoperative status was satisfactory and she expressed a persistent desire to proceed with her pregnancy planning strategy. The doctor decided to proceed with the IUI plan and administered 2 shots after the procedure. The follow-up examination at the polyclinic revealed that the patient did not report any shortness of breath. The chest X-ray result showed a normal bronchovascular pattern (Figure 10).

Discussion

The management of CP has 2 unique objectives: primary and secondary. The primary objective is to evacuate pleural air using aspiration and insert a tube. Secondary objective is administration of hormones after the procedure to suppress secretion of growth hormone. Effective surgical intervention entails blebectomy of all bullae, pleurodesis, pleurectomy, and suturing the diaphragm after excision of all suspected endometriosis lesions [13].

Endometriosis, characterized by development of endometrial glands and stroma outside the uterus, is the most common pathological condition associated with catamenial pneumothorax, but the exact cause is unknown. Endometriosis typically presents as a pelvic cul-de-sac, resulting in various pelvic pain symptoms and reproductive complications. It can present in 4 specific forms within the thoracic cavity: catamenial hemoptysis, endometrial stromal nodules in the visceral pleura or lung tissue, and catamenial hemothorax [10]. The exact mechanism by which ectopic endometrial tissue infiltrates the thorax remains unclear and there are several competing theories. The first theory was proposed by Sampson, who documented the first case in 1927, describing retrograde menstruation with implantation in the peritoneum and transdiaphragmatic migration through fenestrations induced by endometriosis [13]. The second theory involves metastatic spread of endometrial tissue through the venous or lymphatic system to implant elsewhere in the body [8,14]. The third involves coelomic metaplasia of undifferentiated stem cells into endometrial tissue, since both the abdominal and thoracic cavity are covered by the coelomic membrane [14]. The precise etiology of catamenial pneumothorax remains unclear, perhaps because, similar to its intrauterine equivalent, ectopic endometrial tissue is affected by the various phases of the menstrual cycle and can discharge air or blood into the pleural cavity, which can cause recurrent spontaneous hemothorax or pneumothorax. Further influencing factors may include the abrupt rupture of small sacs, the breakage of pulmonary air sacs resulting from the constriction of minor airways due to prostaglandins, and the absence of a protective barrier in the cervix, which permits air to pass from the reproductive system through minute apertures in the diaphragm [6].

Several hypotheses explain the pathogenesis of thoracic endometriosis, including retrograde menstruation, coelomic metaplasia, lymphovascular embolization, and direct transdiaphragmatic migration of endometrial cells [10]. The migration hypothesis suggests that clockwise peritoneal fluid flow directs endometrial cells toward the right hemidiaphragm, where they implant and form lesions [15]. The predominance of right-sided thoracic endometriosis and diaphragmatic involvement in chronic pain support this hypothesis [11]. This is consistent with our case, in which the patient exhibited right-sided pneumothorax with diaphragmatic involvement, supporting the concept of direct transdiaphragmatic migration. Table 1 summarizes selected case reports on catamenial pneumothorax and thoracic endometriosis related to our case.

Similar findings have been reported in a case series published by Marshall et al, in which diaphragmatic implants were observed in 5 out of 8 patients, and diaphragmatic fenestrations were present in 50% of cases [16]. All patients with fenestrations also had diaphragmatic endometrial implants, suggesting that the implants contribute to the development of defects [7]. Furthermore, CP has been reported to occur almost exclusively on the right side, with a prevalence of 100% in a case series by Visouli et al [17] and approximately 90% in other studies [6,18,19]. The preference for the right hemidiaphragm has been attributed to the ‘piston effect’ of the liver, which can create negative pressure that facilitates endometrial migration [16].

Recurrence of CP is a well-documented challenge, with surgical recurrence rates reported to range from 8% to 40% [11]. Pelvic endometriosis often precedes thoracic endometriosis, with studies indicating an interval of up to 5 years before thoracic involvement develops [11]. Our patient had pelvic endometriosis for 10 years and had declined hormonal therapy due to her desire for pregnancy. This prolonged course without hormonal suppression may have contributed to the eventual development of CP, consistent with previous reports showing higher recurrence in patients who did not receive hormonal therapy [20].

Our patient had a long-standing history of pelvic endometriosis, supporting the hypothesis that untreated pelvic disease can eventually progress to thoracic involvement. Clinically, CP is characterized by recurrent pleuritic chest pain, dyspnea, fatigue, and cough, which are strongly linked to menstruation [15]. Spontaneous pneumothorax typically occurs 24–72 hours before or after the onset of menstruation [8]. Endometrial implants are predominantly located in the right hemithorax (87.5–100% in documented cases), but left-sided and bilateral cases have also been reported [15]. Additionally, 18.8–51% of CP cases are associated with concurrent pelvic endometriosis [15,20].

The diagnosis of catamenial pneumothorax (CP) is often delayed due to low clinical suspicion. Women of reproductive age presenting with recurrent spontaneous pneumothorax should be evaluated for CP. High-resolution CT scans may reveal pleural or parenchymal nodules, pneumothorax, pleural effusions, cavitation, or bullae, but endometrial implants are more frequently identified during thoracoscopic assessment [5]. Histological confirmation of endometrial glands and stroma occurs in 53–75% of clinically suspected CP cases [8,21,22]. Additional evidence of the inconsistent findings of endometrial tissue in the thorax is provided by a 2016 report, which indicated the absence of histologic confirmation in all clinically diagnosed cases, despite the presence of morphologic features (nodular deposits and diaphragmatic fenestrations) observed during surgical examination [23].

CP management typically involves a combination of surgical intervention and hormonal therapy. VATS is both a diagnostic and therapeutic procedure, enabling direct visualization of the thoracic cavity, lung parenchyma, and diaphragm for characteristic brown/blue endometrial implants or parenchymal blebs. Surgical interventions include bleb resection and mechanical pleurodesis to prevent recurrence [24]. In our case, pleurodesis surgery was performed to reduce the risk of recurrence, with successful postoperative outcomes.

Hormonal therapy plays a crucial role in long-term recurrence prevention. GnRH agonists, oral contraceptives, and progestins are the primary medical options. GnRH agonists induce a hypoestrogenic state, reducing ectopic endometrial activity, whereas oral contraceptives and progestins maintain hormonal suppression [25]. However, the choice of therapy must be tailored to the patient’s reproductive goals. Studies have shown that hormonal therapy following surgery reduces recurrence, yet recurrence rates remain high, reaching up to 32% after 2 years of follow-up [8]. This case is unique because, due to her desire for pregnancy, the patient did not receive hormonal contraception for endometriosis. However, despite this, her CP progression was delayed for 10 years following a single administration of a GnRH agonist. This is a possible alternative approach for women prioritizing fertility while managing CP.

It is recommended to implement multimodal management and administer gonadotrophin-releasing hormone (GnRH) analog therapy for 6–12 months [25]. GnRH analogs cause hypogonadotropic hypogonadism and amenorrhea to achieve ovarian rest and decrease ectopic endometrial activity [7,8,10,26]. Alifano et al emphasised the necessity of inducing amenorrhea promptly after surgery, as the formation of effective pleural adhesions takes time, and cyclic hormonal fluctuations prior to achieving successful pleurodesis can lead to recurrence [8].

Although significant progress has been made in CP management, infertility remains a challenge for affected women because hormonal therapy, which is typically required to prevent recurrence, can postpone pregnancy attempts. Studies have reported successful IVF outcomes in CP patients receiving GnRH antagonist protocols [11]. However, the impact of ovarian stimulation on CP recurrence remains unclear, as evidence on whether ovulation induction increases CP risk is still inconclusive [29]. Our patient had undergone GnRH agonist treatment for intrauterine insemination (IUI), yet CP progression was significantly delayed, suggesting that short-term hormonal suppression can provide temporary CP control without compromising fertility [27]. During surgery, there were no difficulties removing the endometriosis implant within a diaphragm. A postoperative follow-up chest X-ray showed a satisfactory result, with no evidence of recurrent catamenial pneumothorax.

Future research should focus on comparing different hormonal therapy protocols, including GnRH agonists, GnRH antagonists, and progestins, to determine the most effective approach for managing CP in infertile patients. Additionally, studies should assess the impact of ovarian stimulation on CP recurrence rates to identify safer fertility treatment strategies. Furthermore, the development of surgical techniques specifically tailored for reproductive-aged women is essential to optimize CP treatment while preserving fertility.

Conclusions

In the management of catamenial pneumothorax, clinicians should use a comprehensive approach that incorporates both surgical intervention and tailored hormonal therapy. In patients with diaphragmatic involvement, addressing structural abnormalities through surgical repair can enhance the effectiveness of pleurodesis and reduce recurrence risks. Administering a short course (under 6 months) of a GnRH agonist is recommended for preoperative patients not undergoing surgery during their menstrual cycle, as well as for early postoperative patients, to improve pleurodesis success. In this case, the use of a GnRH agonist contributed to delaying CP progression for 10 years without the need for continuous hormonal suppression. Surgical removal of the endometriosis implant from the diaphragm was successfully performed without complications, and postoperative imaging confirmed the absence of recurrence. These findings suggest that short-term GnRH agonist therapy can be a fertility-preserving alternative for CP management in women prioritizing pregnancy. Further research is needed to determine the optimal duration and timing of GnRH agonist therapy, assess its long-term impact on fertility outcomes, and evaluate the comparative effectiveness of different hormonal and surgical strategies for CP management in infertile women.