Hormone replacement therapy (HRT) is the recommended treatment for premature ovarian failure (POF) to replace the hormones lost due to the condition. HRT should be started at diagnosis and continued until natural menopause age to mimic the natural hormone levels. Full dose long-term HRT has not shown long-term ill effects unlike extended therapy that increases estrogen years. The type of HRT should be tailored to the type of POF, whether prepubertal, spontaneous ovulation may resume for some, or iatrogenic from sudden hormone drop requiring early high dose HRT. Options include oral and transdermal estrogen preparations with progestin.

1. Hormone Replacement Therapy in Premature Ovarian Failure Amita Suneja Professor UCMS & GTBH

2. HRT in POF Vs Natural Menopause True example of replacement therapy Vs extension therapy Started at time of diagnosis AND continued till natural age of menopause No long-term ill effects (WHI study) as estrogen years are not increased Full dose long-term Vs low dose short-term 5-10% will resume spontaneous ovulation & menstruation

3. Tailor HRT According to Type of POF

4. Type I POF - Prepubertal

5. Individualize the Treatment

7. 14 years Turner’s mosaic

8. Counseling of the girl & parents COC pills Occasionally can conceive

10. Types of HRT Regimens

11. Estrogen Preparations- Indian Market Market name Molecule Strength Prep Dose Evalon Estriol succinate 1.0mg Tab 8-16mg/day Premarin CEE 0.625mg Tab 0.625mg/day Progynova Esradiol valerate 1.0mg/2mg Tab 2mg/day Estraderm patch Or Susten 50 Estradiol 25/50/100 ц g patch 1 every 4 days 50 ц g E 2 Gel Or Sandrena gel Estradiol 1.5mg/2.5g 1mg/gm Dermal gel Once a day Estaspray Estradiol 0.375mg Dermal spray 1-3 accutations/day Premarine gel CEE 0.625mg/gm Daily x 2weeks Vaginal gel then twice a week Evalon gel Estriol 1mg/gm E 2 Gel Estradiol 0.025mg/gm

12. Transdermal Estrogens Estragel 1.5mg/2.5g OD EstaSpray 0.375mg BD

13. Currently there appears to be no clear advantage of the transdermal over the oral route Oral estrogens Blood levels Lipoproteins LDL ↓ HDL ↑ Lpa ↓ Prevent oxidation yes TGL ↑ CRP ↑ SHBG, TBHG ↑ Coagulation factors ↑ Transdermal more stable, square dose curve ↓ or same same ↓ or same yes same No effect No effect less effect

14. Progesterone preparations-Indian Market Drug Route Sequential (10-14 days) continuous MPA Oral 5mg daily 2.5mg daily Norethisterone Oral 1mg daily 0.3 mg daily Norethindrone Oral 2.5mg daily 0.5mg daily Dydrogesterone Oral 10mg daily 5mg daily Drospirenone Oral - 2mg daily Natural progesterone Oral 300mg daily 200mg daily Natural progesterone Vaginal 200mg daily 100mg daily Natural progesterone Vaginal gel 45mg daily 45mg daily LNG-IUS Intra-uterine _ 20mcg daily

15. Various options Tibolone Steroid Metabolites are active Mildly estrogenic progestogenic androgenic Amenorrhoea Good for VMS, libido, bones No change in breast density Endometrial bleeding -5% 0.625 mg premarin + MPA 5mg 12 days Estragel/estaSpray + LNG IUS or MPA Angeliq 1 OD

16. Type III POF - Iatrogenic Sudden & precipitous fall of estrogens – severe symptoms VMS, risk of CHD, osteoporosis, suicidal depression Lack of androgens – lack of energy & libido Need to start ET early while in the hospital & full dose or may be higher dose

17. HRT in Surgical Menopause

18. HRT in Cancer Survivors

19. Stem Cell Transplant - POF

20. HRT - POF

21. Premature ovarian failure Not your failure