Efficacy, Safety, and Tolerability of Higher Doses Estrogen Therapy in Women With Premature Ovarian Insufficiency

Browse trials for

• Menopause, Premature 128
• Primary Ovarian Insufficiency 172

Study arms

• Other
  Transdermal estradiol gel 0.1% 1.5mg/ day

  Patient will be given Hormone Replacement Therapy (HRT) in the form of: Transdermal estradiol gel 0.1% 1.5mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.

  Drug: Transdermal estradiol gel 0.1% 1.5mg/ day · Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

• Other
  Transdermal estradiol gel 0.1% 2.0mg/ day

  Patient with insufficient effect from previous treatment estradiol gel 0.1% 1.5mg will be given HRT in the form of: Transdermal estradiol gel 0.1% 2.0mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.

  Drug: Transdermal estradiol gel 0.1% 1.5mg/ day · Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

Interventions

• DrugTransdermal estradiol gel 0.1% 1.5mg/ day

  Estradiol gel 0.1% 1.5mg/ daily + Micronized Progesterone 200mg

• DrugTransdermal estradiol gel 0.1% 2.0mg/ day

  Estradiol gel 0.1% 2.0mg/ daily + Micronized Progesterone 200mg

Primary outcomes

1. Evaluation of the severity of estrogen deficiency symptoms

   The Green scale questionnaire was used initially and after 3 months against the background of HRT. The questionnaire includes 21 questions from 0 to 3 points, where a lower score means a better result.

   Time frame: 3 months

2. Changing the assessment of quality of life using the Short Form Health Survey-36 (SF-36)

   The SF-36 is a generic QoL instrument. It consists of 36 items organized into eight domains: Physical Function (AF), Physical Role Function (RF), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Emotional Role Function (RE), and Mental Health (SM) as well as an item on the change of General Health. The scores of each domain have been converted into a scale from 0 to 100. Lower scores are indicative of worse conditions.

   Time frame: 3 months

3. Changing the assessment of menopause-related quality of life measured using the Menopause-Specific Quality of Life (MENQOL) questionnaire.

   The MENQOL questionnaire is a self-administered instrument. This validated questionnaire (range 1-8) assesses four quality of life domains; physical (16 items), vasomotor (3 items), psychosocial (7 items) and sexual (3 items). Scoring generates 4 domain scores and a total score, the mean of the 4 domain scores. Identical scoring for each of the four MENQOL domains is used. A "0" is identical that the woman has not experienced this specific symptom in the previous month; Score "1" demonstrates that the woman experienced the symptom, but it did not bother her; Scores "2" through "7" demonstrate an increasing level of the bothering symptom, so that these scores indicate increasing levels of bother experienced from the symptom and correspond to the ''1'' through ''6'' checkboxes on the MENQOL. With increasing MENQOL scores, levels of bother experienced from the symptom are increased as well.

   Time frame: 3 months

Secondary outcomes

1. Сhanges in the level of sex hormones after using higher doses estrogen therapy

   Assessment of changes in the level of sex hormone in peripheral blood: estradiol (pmol/l). Reference values: 150 - 450 pmol/l. Blood sampling is performed at baseline and after 3 months.

   Time frame: Assessment of changes in the level of sex hormone in peripheral blood: testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.

2. Сhanges in the level of sex hormones after using higher doses estrogen therapy

   Assessment of changes in the level of sex hormone in peripheral blood: total testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.

   Time frame: 3 months

3. Сhanges in the level of FSH after using higher doses estrogen therapy

   Time frame: 3 months

4. Сhanges in the level of E1 after using higher doses estrogen therapy

   Time frame: 3 months

5. Сhanges in the level of E1S after using higher doses estrogen therapy

   Time frame: 3 months

6. Сhanges in the level of SHBG after using higher doses estrogen therapy

   Time frame: 3 months

7. Bone mineral density (BMD) response to using higher doses estrogen therapy for 12 Months

   Time frame: 12 Months