Prevention of osteoporosis in normogonadotropic anovulatory women

ISRCTN	ISRCTN55207514
DOI	https://doi.org/10.1186/ISRCTN55207514
Secondary identifying numbers	CRE-2009.385-T

Submission date: 22/08/2012
Registration date: 31/08/2012
Last edited: 07/02/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
Anovulation is a condition where the ovary does not release an egg each month as part of a woman's normal cycle in her reproductive years. Anovulatory women usually have oligomenorrhoea or amenorrhoea (irregular or absent menstruation). Anovulatory women of reproductive age need to be protected against bone loss and osteoporosis, a condition that weakens bones, making them fragile and more likely to break. Women with chronic (long-term) anovulation are usually hypoestrogenic (lower than normal level of estrogen), and it is not known whether oral contraceptives or hormone replacement therapy (HRT) have a protective effect on bone loss and the development of osteoporosis. The aim of this study is to compare the effects of oestrogen combined with a progestogen in the form of either an oral contraceptive or HRT on the bone mineral density of anovulatory women.

Who can participate?
Women aged 20-45 with anovulation (either 12 months of amenorrhoea or a menstrual cycle of average length 35 days or longer in the previous 12 months)

What does the study involve?
Participants are randomly allocated to be treated with either the Microgynon oral contraceptive pill or Femoston HRT tablets daily for a period of 12 months. All participants visit the clinic four times during the study for medical tests. Bone mineral density is measured in either the spine or femoral neck (thigh bone) using an x-ray scan. Blood samples are taken at two of these visits.

What are the possible benefits and risks of participating?
The results will help improve medical knowledge. Participants get two free measurements of their bone mineral density, which may help them decide whether to use the treatment long term. Participants also get information from the additional blood tests. All drugs have the potential to cause side effects in some patients. Many women worldwide use either oral contraceptives or HRT. Serious side effects are most commonly found in older women who have underlying health problems, who therefore won’t be included in the study. The most common side effects of both medications are nausea and breast tenderness. During every visit, the investigator closely monitors participants for side effects. The risks of blood drawing are minimal but include the temporary pain of the needle stick, occasional bruising and rarely inflammation of the vein. The study is stopped if participants have unacceptable side effects or adverse reactions. Any significant findings discovered during this study will be provided to participants. Both preparations to be used in this study are commonly prescribed already. They are not new drugs. Both preparations have a low risk of venous thrombosis (blood clots) and breast cancer with long-term use. Venous thrombosis is more common in women at risk, who are usually older and not healthy, not like the women in this study. The researchers believe it is unethical not to treat these women, as if left untreated, they risk endometrial hyperplasia (where the lining of the womb becomes thicker) and premature osteoporosis, with associated fractures, illness and possible death.

Where is the study run from?
The Li Ka Shing O&G clinic (Hong Kong)

When is the study starting and how long is it expected to run for?
September 2009 to September 2012

Who is funding the study?
The Chinese University of Hong Kong

Who is the main contact?
Cindy Law
cindylaw@cuhk.edu.hk

Contact information

Prof Christopher Haines
Scientific

The Chinese University of Hong Kong
Prince of Wales Hospital
Shatin
-
Hong Kong

Study information

Study design	Prospective randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A pilot study to compare the effect of oestrogen combined with a progestogen in the form of either an oral contraceptive (OC) or hormone replacement therapy (HRT) on bone mineral density (BMD) in normogonadotropic hypoestrogenic anovulatory women
Study hypothesis	That oral contraceptives and hormone replacement therapy are equally effective in preventing osteoporosis in normogonadotropic anovulatory women.
Ethics approval(s)	Clinical Research Ethics Committee of the Chinese University of Hong Kong, 23/08/2009, ref: CRE-2009.385-T
Condition	Osteoporosis
Intervention	Randomization to treatment with either: 1. Microgynon 30 ED OC (ethinylestradiol 0.03 mg, levonorgestrel 0.15 mg daily for 21 days with 7 days lactose tablet) 2. Femoston (oestradiol 2 mg daily for 14 days, oestradiol 2 mg daily plus dydrogesterone 10 mg daily for 14 days)
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ethinylestradiol, levonorgestrel, oestradiol, dydrogesterone
Primary outcome measure	BMD in either spine or femoral neck, measured using dual-energy x-ray absorptiometry (DEXA)
Secondary outcome measures	1. Estimate of bone formation by measurement of serum bone-specific alkaline phosphatase (sBSAP) 2. Estimate of bone resorption by measurement of serum degradation products of C-terminal telopeptides of type 1 collagen (sCTX) 3. Well-being, measured using the Women's Health Questionnaire (WHQ)
Overall study start date	16/09/2009
Overall study end date	30/09/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	100
Participant inclusion criteria	1. Women aged 20-45 years 2. Either 12 months of amenorrhoea or a menstrual cycle of average length 35 days or longer in the previous 12 months 3. At baseline Follicle-stimulating hormone (FSH) > 3.5 IU/L, < 10 IU/L 4. Luteinizing hormone (LH) > 2.4 IU/L, < 12.6 IU/L 5. E2 < 201 pmol/L 6. PRL < 496 mIU/L
Participant exclusion criteria	1. On exogenous hormones within previous 3 months 2. Any contraindication to the use of female hormones 3. Any condition making it likely that they cannot complete the study 4. Hypergonadotropic or hypogonadotropic hypogonadism or hyperprolactinaemia as defined by abnormal FSH, LH or Prolactin concentrations 5. Any personal or strong family history of breast cancer or endometrial cancer 6. History of pulmonary or venous thromboembolism
Recruitment start date	16/09/2009
Recruitment end date	30/09/2012

Locations

Countries of recruitment

Hong Kong

Study participating centre

The Chinese University of Hong Kong

Shatin
-
Hong Kong

Sponsor information

The Chinese University of Hong Kong (Hong Kong)
University/education

Direct Grant for Research
Medicine Panel
Shatin
-
Hong Kong

Website	http://www.cuhk.edu.hk/english/
"ROR"	https://ror.org/00t33hh48

Funders

Funder type

University/education

Chinese University of Hong Kong (ref: 2041471)
Government organisation / Universities (academic only)

Alternative name(s): The Chinese University of Hong Kong, 香港中文大学, CUHK
Location: Hong Kong

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

07/02/2017: Plain English summary added.