Primary Amenorrhoea - Causes
- Chromosomal 50%
- Hypothalamic 20%
- Mullarian 15%
- Anatomic 5%
- Pituitary 5%
- Other 5%
Primary amenorrhoea - Definition
- No menses by 15 with normal secondary sex characteristics
- No menses by 13 without secondary sex characteristics
Hypergonadotrophic primary amenorrhoea - Causes
Turner’s syndrome Structurally abnormal X chromosome Pure gonadal dysgenesis Enzyme deficiencies Mosaicism
Hypogonadotrophic primary amenorrhoea - Causes
Physiological delay
Kallmans syndrome
CNS tumours
Chronic disease
Amenorrhoea with secondary sex characteristics
ANATOMIC: - Hymen - AIS -True Hermaphrodite NON-ANATOMIC - Ovarian insufficiency - Iatrogenic - Autoimmune - Glalactoaemia - Savage syndrome (Gonadotrophin resistant ovary)
Secondary amenorrhoea - Causes
- Pregnancy
- Ovarian 40% (PCOS, prem insufficiency [chemorad/turners/autoimmune/fragile x premutation])
- Hypothalamic 35% (functional, infiltrative)
- Pituitary 20% (prolactinoma, sella mass, sheehans, radiation)
- Uterine 5%
- Thyroid dx
Delayed puberty
- Anatomic - Rokitanski, obstruction
- Hypergonadotropic
- Gonadal dysgenesis (turner’s, 46XX, 46 XY)
- Early gonadal failure - Hypogonadotrophic
- Constitutional
- infiltrative lesion
- Kallmans (anosmia and colour blindness)
- chemorad
- hypothyroidism
- drugs
- Chronic disease
Precocious puberty - Causes
- CENTRAL
- Idiopathic
- Tumours
- Infection
- Trauma
- Congenital abn e.g. hydrocephalus - PERIPHERAL
- HYPOgonadotrophic
* isosexual = oestrogenic neoplasm (e.g. McCune albright [fibrous dysplsia, cafe au lait patches and hyperfunctioning endocrinopathies])
* heterosexual = androgenic tumour or CAH
- HYPERgonadotropic
* GnRH or BHCG [similar to LH] secreting tumour
*** Premature adrenarche may be the first sign of PCOS
Precocious puberty - Definition
Development of secondary sex characteristics earlier than expected i.e. 2SD < mean. Usually 8 in girls and 9 in boys.
Endometriosis - Level A evidence for Infertility
- Rx grade I/II with excision or ablation
- No role for hormonal therapy (either primary or adjunct to surgery)
- Endometriomas:
- no benefit to remove if >3cm in ART context
- if removing cystectomy is better than drainage
Endometriosis - Other levels of evidence for Infertility
B:
- GnRH for 3-6/12 prior to ART improves clinical pregnancy
C:
- Stage III/IV laser coat better than monopolar in sport pre rates
- IUI and ovarian hyperstim increases live birth rates )Stage I/II)
- Recurrence not increased by IVF/ICSI
Endometriosis - Level A evidence for Pain
- Progestagens and antoprogestagens effective
- GnRH antagonists (Groerelin) + add back effective
- Endometrioma:
- COCP for secondary prevention
- cystectomy > drainage
- Surgery:
- No role for preop or post op hormonal Rx
- DO NOT use LUNA
- Mirena 1-2y secondary prevention dysmenorrhoea
- Presacral neurotomy is difficult but effective
Endometriosis - Other levels of evidence for Pain
B:
- COCP
- Mirena IUD
- Surgery for deep end, but 2% intro complication rate
- Aromatoase inhibitors (w Prog, COCP or GnRH ant)
- Endometrioma - excision lower recurrence rate
C:
- Ring or patch
GPP:
- Hysterectomy for those who’ve completed their family and have failed medical therapy
Components of the prognostic scoring system for persistent trophoblastic disease
- Age = old worse
- BHCG level = higher worse
- Outcome of index pregnancy = term worse than MC worse than molar preg
- Time from index pregnancy = longer has worse outcome
- Size of residual tissue = bigger is worse
- Metastatic disease = liver/brain worse than GIT worse than spleen/kidneys worse than lungs
- Previous CTX (double agent worse than single)
Will guide decision of MTX or EMA-CA or EMA-EP +/- RTx.
XY Females
- AIS (no androgen receptors so no hair)
- Gonadal dysgenesis (NO secondary sex characteristics)
- 5 alpha reductase deficiency (No DHT so no prostate/penis, but male secondary sex characteristics)
Requirements for Gillick Competence
- Unable to convince parents
- Likely to engage in sexual activity regardless of contraception
- Able to understand advice given
- Contraception required for physical or mental health
- In the patients best interest
- No lower age limit
PCOS - Rotterdam Criteria
2/3: *need all 3 in adolescents
- Polycystic ovaries (>11 follicles in EACH ovary, 2-9mm, OR >10mL)
- Hyperangrogenism (clinical or biochemical)
- Oligoamenorrhoea
Present in 15% of women.
PCOS - Pathogenesis
Incompletely understood
Complex hormonal and biochemical alterations
- Genetics (70%) and environmental
- Increased LH and LH pulse frequency, and enhanced ovarian sensitivity to LH
- Increased insulin resistance > increased androgens and decreased SHBG
Pregnancy risks of PCOS
GDM (~50%)
Miscarriage (mostly secondary to obesity)
PIH
SGA
Long term risks of PCOS
- Endometrial cancer RR 2.7
- Type II DM RR 4
- CV disease
- OSA
- Anxiety/depression
Differential diagnoses for PCOS
- Hyperprolactinaemia
- Cushings disease
- late onset CAH
- Hypothyroidism
- Androgen secreting adrenal tumour
Congenital Adrenal Hyperplasia - Presentation
- Classical
- Virilised female baby
- Hyponaturamia and hyperkalaemia secondary to aldosterone deficiency - Non-classical
- Precocious or normally times heterosexual puberty
- PCOS like syndrome
Congenital adrenal hyperplasia - Mechanism
21-hydroxylase is the most commonly affected enzyme
Usually converts 17-OH-progesterone to 11-deoxycortisol > cortisol (and aldosterone). (17-OH-P is also the substrate for androstenedione).
Without cortisol no negative feedback, so higher ACTH and more substrates into androstenedione.
Congenital adrenal hyperplasia - Rx
Dexamethasone/Prednisone for pathway supression
COCP
Ovulation induction if required
