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Transgender in Gynaecology: Counselling, Management, and Fertility Preservation Options

1. Definitions and Terminology

• Campbell Walsh Wein Urology, p. 2180
• Tietz Textbook of Laboratory Medicine 7th Ed, p. 2377

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2. Counselling Principles in Gynaecological Practice

A. Creating an Inclusive Environment

• Use the patient's preferred pronouns and name at every encounter - incorrect gendered language is a major driver of health disparities and avoidance of care
• Nearly 20% of transgender patients have been refused care and 23% avoid necessary care (including cervical cancer screening) due to fear of discrimination
• A non-judgmental approach and affirming environment reduce these barriers
• Collect accurate sexual orientation and gender identity (SOGI) data in the medical history

B. WPATH Standards of Care (SOC v8) Framework

1. Reversible steps first: Social transition (name, pronouns, clothing)
2. Partially reversible: Gender-affirming hormone therapy (GAHT)
3. Irreversible: Surgical procedures (gonadectomy, vaginoplasty, hysterectomy, phalloplasty)

• 1 year of continuous gender-affirming hormone therapy (unless contraindicated)
• Two referral letters from qualified mental health or healthcare professionals documenting:
  • Persistent gender incongruence
  • Capacity to give fully informed consent
  • Any medical/mental health concerns are addressed
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry, p. 6322

C. Multidisciplinary Team

• Gynaecologist/obstetrician - reproductive health, cancer screening, hormones
• Endocrinologist - hormone management
• Mental health professional - psychological evaluation and support
• Urologist - lower urinary tract and genital surgery
• Fertility specialist - gamete/tissue preservation counselling

D. Psychological Counselling

• Address body dysmorphia, depression, anxiety - significantly elevated in transgender individuals
• Suicidality rates are markedly higher in the transgender population compared to cisgender peers
• Psychotherapy prior to transition is associated with improved outcomes
• Safer sex counselling and STI/HIV risk reduction should be provided

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3. Gynaecological Management of Transgender Men (FtM/Assigned Female at Birth - AFAB)

A. Preventive Care (often missed due to care avoidance)

• Cervical cancer screening (Pap smear): Transgender men with a cervix remain at risk for cervical cancer (especially if HPV-positive or history of WSW/MSM sexual activity). There is a mistaken belief that transgender men are not at risk. Pap smears should continue per standard guidelines as long as the cervix is present.
• Breast/chest cancer screening: Risk exists if mastectomy has not been performed; mammography recommendations apply
• Bone health: Testosterone therapy and/or oophorectomy increase osteoporosis risk; DEXA screening indicated

B. Gender-Affirming Hormone Therapy (Testosterone)

• Cessation of menses (usually within 6-9 months)
• Clitoromegaly (may make metoidioplasty feasible)
• Deepening of voice (permanent after 1-2 years)
• Increased muscle mass, facial/body hair, acne
• Male-pattern hair loss (in genetically predisposed individuals)
• Decreased fertility (may be temporary or permanent)

• Target: serum testosterone 320-1000 ng/dL (normal male range)

• Testosterone, LH (HPG axis suppression), estradiol, CBC every 3-4 months in the first year
• Annual monitoring thereafter including lipid panel
• Note: hemoglobin rises (erythrocytosis is the most common adverse effect); check for sleep apnea/smoking if polycythemia occurs
• Serum creatinine will increase (mirrors increased muscle mass) - interpret with male reference ranges

C. Gender-Affirming Surgical Options (AFAB)

• "Top" surgery: Mastectomy and male chest construction (can be done before hormones)
• "Bottom" surgery:
  • Metoidioplasty: Release of hypertrophied clitoris to create a neophallus
  • Phalloplasty: Construction of a larger phallus with grafted tissue + urethral extension + scrotoplasty + vaginectomy
  • Hysterectomy and bilateral salpingo-oophorectomy: Usually performed as part of lower surgery, or as a standalone gender-affirming procedure
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry, p. 6330
• Campbell Walsh Wein Urology, p. 2180

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4. Gynaecological Management of Transgender Women (MtF/Assigned Male at Birth - AMAB)

A. Preventive Care

• Prostate screening: Remains indicated - prostate is retained unless removed; estrogen therapy and androgen suppression may lower PSA but prostate cancer risk persists
• Breast cancer screening: After years of estrogen therapy, breast cancer risk increases; mammography should be offered per guidelines
• Thromboembolic risk: Elevated with estradiol use; prefer transdermal over oral formulations to reduce first-pass hepatic clotting factor stimulation

B. Gender-Affirming Hormone Therapy (Estradiol + Anti-androgen)

• Breast development, feminization of fat distribution, skin softening
• Risks: VTE, hypertriglyceridemia, cholelithiasis
• Transdermal patch carries lower VTE risk than oral (avoids first-pass metabolism)

• Spironolactone (most common in US): Androgen receptor antagonist + mineralocorticoid effect
• Bicalutamide: Androgen receptor blocker
• Leuprolide depot: Suppresses gonadotropin production (GnRH agonist)
• Cyproterone acetate: Available outside US
• Micronized progesterone: Suppresses testosterone; may augment breast development (given at bedtime due to mild sedation)

• Estradiol, total testosterone every 3-4 months initially
• Lipid panel, CBC, hepatic function annually
• Transgender women on estrogen: hemoglobin falls - interpret using female reference intervals to avoid false diagnosis of anemia

C. Gender-Affirming Surgical Options (AMAB)

• "Top" surgery: Breast augmentation (if insufficient breast development with hormones alone)
• "Bottom" surgery (penile inversion vaginoplasty): Penectomy + orchiectomy + vaginoplasty + clitoroplasty + labiaplasty
• After orchiectomy: anti-androgen therapy can be discontinued; lower estradiol dose may suffice
• Facial feminization surgery, voice training (pitch, intonation, articulation, resonance)

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5. Fertility Preservation - The Key Counselling Priority

• Goldman-Cecil Medicine, p. 2529

A. Fertility Preservation in Transgender Women (AMAB)

B. Fertility Preservation in Transgender Men (AFAB)

C. Key Counselling Points for Fertility

1. Timing: Fertility preservation must be discussed at the first clinical contact, before initiating any GAHT
2. Reversibility uncertainty: Testosterone-induced amenorrhoea may be reversible on stopping, but long-term effects on ovarian reserve are uncertain; some degree of subfertility may persist
3. Gestational options if uterus is retained: transgender men can carry pregnancies after stopping testosterone
4. Third-party reproduction: Surrogacy (for transgender women who have stored sperm) or gestational carrier options
5. Legal and ethical counselling: Parentage laws vary; recommend consultation with a reproductive lawyer
6. Psychological impact: Fertility counselling may trigger significant gender dysphoria (e.g., discussing egg retrieval or pregnancy in a transgender man); sensitive, individualized counselling is essential
7. Cost and access barriers: Fertility preservation is expensive and not universally covered by insurance

• Goldman-Cecil Medicine
• Ausavarungnirun C & Orwig KE. Gonadal tissue cryopreservation in transgender and gender-diverse people. Reproduction, 2024 [PMID: 39331789]
• Minnihan A et al. Fertility Preservation for Transgender and Gender-diverse Individuals. Clin Obstet Gynecol, 2025 [PMID: 40804762]

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6. Health Disparities and Special Considerations

• Rosen's Emergency Medicine, p. 3545

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7. Summary: Gynecologist's Role at a Glance

1. Affirm identity - use correct name/pronouns; create a safe environment
2. Assess for gender dysphoria with multidisciplinary team
3. Counsel on GAHT - risks, benefits, monitoring, effects on reproductive organs
4. Fertility preservation discussion - mandatory before any GAHT/surgery
5. Continue cancer screening - cervix, breast, prostate as anatomically indicated
6. Manage GAHT complications - VTE, polycythemia, metabolic changes
7. Coordinate surgery - hysterectomy, oophorectomy, vaginoplasty as needed per WPATH SOC v8 criteria
8. Provide ongoing psychological support throughout transition

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• Goldman-Cecil Medicine International Edition, Vol. 2
• Tietz Textbook of Laboratory Medicine, 7th Ed.
• Campbell Walsh Wein Urology, 3-Volume Set
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry
• Rosen's Emergency Medicine, Concepts and Clinical Practice
• Minnihan A et al. Fertility Preservation for Transgender and Gender-diverse Individuals. Clin Obstet Gynecol, 2025 [PMID: 40804762]
• Ausavarungnirun C, Orwig KE. Gonadal tissue cryopreservation in transgender and gender-diverse people. Reproduction, 2024 [PMID: 39331789]
• Serra P et al. From Transition to Reproduction: A Narrative Review of Evolving Evidence in Transgender Obstetrics and Gynecology. Gynecol Obstet Invest, 2026 [PMID: 41961737]

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Recent Advances in PCOS (Polycystic Ovary Syndrome)

1. Updated Diagnostic Criteria - 2023 International Evidence-Based Guideline

Anti-Müllerian Hormone (AMH) as a Diagnostic Criterion

• AMH has been added as a surrogate for polycystic ovarian morphology (PCOM) on ultrasound
• Diagnosis in adults still requires 2 of 3 features: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and PCOM/elevated AMH
• This is particularly useful when transvaginal ultrasound is not feasible or acceptable (e.g., adolescents, nulliparous women)

Revised Ultrasound Threshold

• Updated follicle count threshold raised to ≥20 follicles in either ovary (previously ≥12) using modern high-frequency probes
• Ovarian volume >10 mL remains a criterion on older equipment

Adolescent Diagnosis

• Stricter in adolescents: requires both persistent anovulation AND clinical/biochemical hyperandrogenism
• Ovarian morphology and AMH are NOT used in adolescents (<8 years post-menarche) to avoid over-diagnosis
• Berek & Novak's Gynecology, p. 1919
• Stener-Victorin et al. Nat Rev Dis Primers 2024 [PMID: 38637590]

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2. New Pathophysiological Insights

A. AMH as a Neuroactive Hormone

• Emerging evidence shows AMH is not just a marker of ovarian reserve but may directly act on GnRH neurons in the hypothalamus
• Elevated AMH in PCOS stimulates GnRH hyperpulsatility → elevated LH → androgen excess
• This "AMH-GnRH-LH" axis represents a fundamentally new understanding of PCOS pathogenesis
• Dokras A. Fertil Steril 2025 [PMID: 40992713]

B. Neurokinin-Kisspeptin (NKB) Axis

• Hyperactivation of the KNDy neurons (kisspeptin/neurokinin B/dynorphin neurons in the hypothalamus) drives increased GnRH pulsatility
• This is upstream of the entire reproductive axis
• Neurokinin-3 receptor (NK3R) antagonists (e.g., fezolinetant, ESN364) are in clinical trials - they reduce LH pulsatility and testosterone without suppressing the axis entirely
• Dong J, Rees DA. BMJ Med 2023 [PMID: 37859784]

C. 11-Oxygenated Androgens

• Beyond the classic androgens (testosterone, DHEAS), women with PCOS have high levels of 11-oxygenated androgens (11-ketotestosterone, 11-ketodihydrotestosterone) produced by the adrenal gland
• These have high androgenic potency and may better explain metabolic risk than serum testosterone alone
• Current testosterone assays miss these - mass spectrometry-based testing may be needed for accurate phenotyping

D. Gut Microbiome Dysbiosis

• Growing evidence links altered gut microbiota in PCOS to:
  • Increased intestinal permeability → endotoxemia → chronic low-grade inflammation
  • Impaired short-chain fatty acid (SCFA) production → worsened insulin resistance
  • Possible link to mood disorders and depression via the gut-brain axis (gut dysbiosis may partly explain the high rates of anxiety and depression in PCOS)
• Butyrate-producing interventions (dietary fiber, prebiotics, probiotics) are emerging as adjunct strategies
• Dokras A. Fertil Steril 2025 [PMID: 40992713]

E. Epigenetic and In Utero Programming

• PCOS is now considered partly an epigenetic disorder
• Prenatal androgen exposure in animal models causes PCOS-like phenotype in offspring
• DNA methylation and histone modification changes in granulosa cells and adipose tissue are active research areas
• Dong J & Rees DA. BMJ Med 2023 [PMID: 37859784]

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3. Advances in Pharmacological Treatment

A. GLP-1 Receptor Agonists (GLP-1 RAs) - The Biggest Advance

• Multiple systematic reviews and meta-analyses (2024-2026) confirm efficacy:
  • Zhou et al. BMC Endocr Disord 2023 - GLP-1 RAs improved pregnancy rate and menstrual cyclicity [PMID: 37940910]
  • Forslund et al. Eur J Endocrinol 2026 - most recent systematic review confirms benefit [PMID: 41701618]
  • Lin et al. Sci Rep 2025 - meta-analysis confirms weight and metabolic parameter improvement [PMID: 40360648]
  • An RCT (Chen et al. 2025) showed combined semaglutide + metformin outperformed either alone for weight, metabolic, and reproductive outcomes in obese PCOS women [PMID: 40713699]
• Not yet formally licensed for PCOS specifically but widely used off-label; expected to feature in updated guidelines

B. Inositols - Expanded Evidence

• myo-Ins: Enhances FSH receptor and aromatase expression → supports folliculogenesis and estrogen synthesis
• DCI: At high levels, stimulates androgen synthesis in theca cells and downregulates aromatase - actually worsens hyperandrogenism
• Optimal ratio: myo-Ins : DCI = 40:1 (mirrors the physiological plasma ratio) - this combination improves reproductive outcomes even in women without insulin resistance
• α-Lactalbumin co-administration significantly improves inositol intestinal absorption
• Inositols are gaining recognition as safer than metformin with comparable efficacy in certain phenotypes
• Lentini et al. Drug Des Devel Ther 2025 [PMID: 40420946]

C. SGLT2 Inhibitors (Sodium-Glucose Co-transporter 2 Inhibitors)

• Reduction in insulin resistance and body weight
• Improvement in testosterone levels and menstrual regularity
• Reduction in hyperinsulinemia independent of weight loss
• Synergistic effect when combined with metformin
• Still largely based on small RCTs and pilot studies; larger trials ongoing

D. NK3R Antagonists (Neurokinin-3 Receptor Blockers)

• Fezolinetant (approved for menopausal hot flashes) and related compounds act upstream on KNDy neurons
• In Phase 2 PCOS trials, they reduced LH pulsatility and serum testosterone without hypoestrogenic side effects
• Represent a potentially targeted, mechanism-based treatment - not yet approved for PCOS

E. Updated Role of Letrozole

• Letrozole (aromatase inhibitor) is now firmly first-line for ovulation induction over clomiphene citrate, confirmed by multiple guidelines including WHO and NICE
• Higher live birth rates and lower multiple pregnancy rates than clomiphene
• Harrison's Principles of Internal Medicine 22E, p. 3178

F. Anti-Androgens - New Options

• Flutamide and bicalutamide: Non-steroidal androgen receptor blockers, effective for hirsutism with a favorable profile
• Clascoterone (topical androgen receptor antagonist): Emerging for acne in PCOS
• Society for Endocrinology 2025 Guideline now recommends systematic evaluation for combined oral contraceptive (COC) failure before adding anti-androgens [PMID: 40364581]

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4. Cardiovascular Risk - New Recognition

• Women with PCOS have a 7-fold increased risk of myocardial infarction and elevated stroke risk even in reproductive years
• Elevated PAI-1 (impaired fibrinolysis), dyslipidemia (low HDL2α, high triglycerides), and hypertension (reaching 40% by perimenopause) are key contributors
• Cardiometabolic screening is now recommended at diagnosis and at regular intervals thereafter
• Berek & Novak's Gynecology, p. 1922

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5. PCOS and Mental Health - New Emphasis

• High prevalence of depression, anxiety, eating disorders, and negative body image is now formally part of the PCOS burden
• The 2023 Guideline mandates screening for mental health disorders at diagnosis and follow-up
• Emerging neuroimaging data show differences in cognitive function and brain structure in PCOS vs. controls
• Gut dysbiosis may partly mediate the mental health burden (gut-brain-ovary axis)

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6. PCOS in Pregnancy - Recent Evidence

• Increased risk: early miscarriage, gestational diabetes (3-fold), gestational hypertension, preeclampsia, preterm birth
• Letrozole preconception and lifestyle optimization reduce pregnancy complications
• Metformin in pregnancy: Does NOT prevent gestational diabetes or pregnancy loss in PCOS per recent RCTs - not recommended for this purpose
• AMH monitoring during ovarian stimulation helps titrate gonadotropin doses and predict OHSS risk

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7. Emerging/Future Directions

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Summary Table: Key Recent Advances

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• Stener-Victorin E et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2024 [PMID: 38637590]
• Dokras A. PCOS in 2025 - insights and innovations. Fertil Steril 2025 [PMID: 40992713]
• Dong J & Rees DA. PCOS: pathophysiology and therapeutic opportunities. BMJ Med 2023 [PMID: 37859784]
• Lentini G et al. PCOS and Inositols. Drug Des Devel Ther 2025 [PMID: 40420946]
• Forslund M et al. GLP-1 RA in PCOS. Eur J Endocrinol 2026 [PMID: 41701618]
• Harrison's Principles of Internal Medicine 22E, p. 3178
• Berek & Novak's Gynecology, pp. 1919-1922