What is the management approach for Swyer syndrome?

Management of Swyer Syndrome

Bilateral prophylactic gonadectomy should be performed as soon as the diagnosis is established, followed by lifelong hormone replacement therapy to induce and maintain pubertal development and optimize bone health. 1, 2

Immediate Surgical Management

The cornerstone of management is early bilateral gonadectomy due to the 30-35% risk of malignant germ cell tumor development in dysgenetic gonads. 1, 2

• Laparoscopic bilateral gonadectomy is the preferred surgical approach for streak gonad removal, offering minimally invasive definitive treatment 3
• Surgery should be performed promptly after diagnosis confirmation, ideally before malignant transformation occurs 1, 2
• The most common malignancies include gonadoblastoma, dysgerminoma, and rarely choriocarcinoma, with choriocarcinoma carrying particularly poor prognosis 4
• If adnexal masses are already present at diagnosis (suggesting possible malignancy), exploratory laparotomy may be necessary instead of laparoscopy 3
• When neoplasm precedes the diagnosis of gonadal dysgenesis, oncological treatment should be introduced with parallel gonadectomy 4

Diagnostic Confirmation

Before proceeding with gonadectomy, confirm the diagnosis through:

• Karyotype analysis demonstrating 46,XY chromosomal constitution (or mosaic patterns like 46,XY/45,X) 3
• Hormonal evaluation showing hypergonadotropic hypogonadism with elevated FSH (mean ~96 mIU/L) and LH (mean ~24 mIU/L), with low estradiol, testosterone, and anti-Mullerian hormone levels 2, 3
• Pelvic imaging (ultrasound initially, MRI for problem-solving) demonstrating hypoplastic uterus, absent ovaries, and streak gonads or dysplastic cystic structures 2
• Rule out testes or testes-like structures in abdomen, pelvis, or inguinal regions 2

Hormone Replacement Therapy

Initiate estrogen replacement therapy immediately after gonadectomy (or at diagnosis if surgery is delayed) to induce puberty and prevent osteoporosis. 1

• Begin hormone replacement early to achieve optimal bone mineral accumulation during the critical adolescent years 1
• Therapy is required lifelong to maintain secondary sexual characteristics and bone health 1
• The goal is to induce and maintain typical pubertal development in phenotypically female patients 1

Fertility Counseling and Options

• Pregnancy is achievable through oocyte donation with outcomes similar to women with 46,XX ovarian failure 1
• Patients should receive counseling about fertility options early in their care 1
• The uterus, though hypoplastic, can support pregnancy with appropriate hormonal support 2

Long-Term Follow-Up

• Patients require lifelong follow-up in specialist centers with multidisciplinary teams including endocrinology, gynecology, genetics, and mental health support 1
• Monitor bone mineral density regularly given the risk of osteoporosis without adequate hormone replacement 1
• Provide psychological support for issues related to diagnosis disclosure, gender identity, and infertility 1

Critical Pitfalls to Avoid

• Delayed gonadectomy significantly increases malignancy risk—do not postpone surgery once diagnosis is confirmed 1, 2
• Inadequate or delayed hormone replacement leads to poor bone health and incomplete pubertal development—start therapy early 1
• Missing the diagnosis during initial workup for primary amenorrhea or delayed puberty, allowing patients to present later with adnexal masses representing advanced malignancy 3
• Failing to screen siblings, as familial cases occur 3