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Menstrual bleeding, puberty and Menopause
Nadeem Kasmanion 13 September 2011
Transcript of Menstrual bleeding, puberty and Menopause
> Tranformation of a girl
into a fertile women.
> Puberty when Normal, comprises
- an adolescent growth spur
- the acquistion of secondary sexual characters
- the onset of menstruation (menarche)
- the establishment of ovulatory function. Endocrine changes during Puberty
Reactivation of the HPO axis > Puberty Begins
HPO axis awakens after being dormant through childhood
>In childhood, the Hypothalamus and the Pituitary are extremely senstitive to suppression by the gonadal steroids. When puberty begins, this sensitivity is lost.
Sleep related, pulsatile release of gonadotropins is the first recognised endocrine event.
With the progression of Puberty, the pulsatile release converts to a continous release 24 hrs a day.
The gonadotropins that are released, lead to the production of ovarian estrogen, which initiates the physical changes of puberty.
Ovarian changes are evident at a very early age. Signs of puberty
Growth Spurt is an early feature
Subareolar breast bud appears (thelarche)
Breast development is primarily under the control of ovarian estrogen
After the development of the breast bud, the formation of pubic and axillary hair growth occurs. This is mainly under the influence of ovarian and adrenal androgens
Menarche is a late feature in the course of puberty B1 Pre Pubertal B2 Breast Bud B3 Juvenile Smooth Contour B4 Areola and papilla project above breast B5 Adult Tanner stages of breast development Tanner stages of pubic hair development Progression through Puberty
95% of the normal girls will attain stage 2 breast development by the age of 13.2 years.
50% will complete all stages of puberty within 2-3 years
97% will complete all stages of puberty within 5 years
-Bone age is an index of physiological maturation and it correlates closely with the menarche.
80% of the girls begin to menstruate at a bone age of 13-14 years
- After Menarche, Menstrual cycles tend to be irregular as ovulation is initially infrequent. Its takes several months for most girls to have a regualr cycle
Menopause > 'last menstrual period'
Avg age of Menopause in the UK is 50.8 years
a women undergoes 400 cycles during an average lifetime
a newborn girl will have half a million oocytes in her ovaries > one third of these are lost during puberty and the remainder are lost in the reproductive life
Hormonal Changes in Menopause
In premenopausal women, estradiol is produced by the granulosa cells of the developing follicle
As menopause approaches, the production of estradiol becomes variable > the proportion of anovualatory menstrual cycles increases and the progesterone production declines > There is a rise in pituitary production of LH and FSH becasue of diminished negative feedback from estrogen and other ovarian hormones such as inhibin > Serum levels of FSH above 30 IU/I can be used clinically to clarify the diagnosis of menopause. Anti-Mullerian hormone is a better marker of follicular reserve as compared to FSH.
After Menopause, the predominant circulating estrogen estrone (less potent form of estrogen than estradiol) Signs and Symptoms Of Menopause
Vaginal Bleed: Menopause can be recognised after a period of 6 mnths to a year of amenorrhoea. Irregular periods before menstruation are beacuse of anovulatory cycles. Incase if the irregular bleeding continues, endometrial assesment to exclude endometrial carcinoma may be required.Post menopausal bleeding also requires endometrial assesment.
Hot Flushes: It is an uncomfortable subjective feeling of warmth in the upper part of the body, usually lasting around 3 mins. They are sometimes accompanied by nausea, palpitation and sweating.Exogenous estrogen administration, in the form of HRT is effective in relieving these symptoms in about 90% of cases.
Genitourinary atrophy: The genital system, urethr and bladder trigone are estrogen dependent and undergo gradual atrophy after menopause. Thinning of the vaginal skin may cause dyspareunia and bleeding. Loss of vaginal Glycogen causes a rise in pH which can predispose to local infection. The atrophic changes in the trigone may respond very well to a short course of local or systemic estrogen Long-term effects of Menopause
Breast cancer: The risk of BC increases with incerease in age and slows after menopause. A women who attains menopause late has double the risk of having BC as compared to a women who attains Menopause early.
Osteoporosis: Menopause increases the osteoclastic activity.
>> In the first 4 years after the menopause there is an annual loss of 1-3% of bone mass, falling to 0.6% per year after that >> due to this there is an increase rate of fractures, particularly to the distal radius, the vertebral body and the upper femur.
>> Wedge compression fractures of the spine leads to Dowager;s hump.
HRT has a very significant benefit in reducing the incidence of osteoporosis and osteoporotic fractures. Diagnosis
Menopause may be confused with premenstrual syndrome (PMS), depression, thyroid dysfunction, pregnancy, etc.
The Diagnosis of menopause is usually clinical and can only be made in retrospect after 6-12 months of amenorrhoea.
If there is confusion regarding the diagnosis then serum FSH should be checked. If it is >30IU/I postmenopausally. Hormonal Therapy
Estrogen supplementation is the basis of replacement therapy. Progesttogens may have a small role in relieving vasomotor symptoms, they are added to estrogen to protect the endometrium and reduce the hyperplasia.
Estrogen can be administered as - daily oral tablet daily - twice weekly - or weekly transdermal patches - Subcutaneous implants every 6-8 months - Daily nasla sprays and skin creams - 3 monthly vaginal rings.
Women who have not undergone hysterectomy or women who have undergone hysterectomy should be placed on a regimen which includes a progestogen to minimise the risk of endometrial cancer associated with unoppposed estrogen therapy. Oral preparations
Oral route has a good impact on lipid profile, leading to higher HDL and lower LDL, but it is potentially more thrombotic
Estrogen only tablets
Estrogen - Progestogen tablets > admin cyclically or continously
Tibolone and Raloxifene are alternatives to the estrogen - progesterone preparation.
Tibolone is a synthetic steroid with weak estrogenic, progestogenic and androgenic effetcs, which may be started 2 years after periods have ceased
Raloxifene is a synthetic selective estrogen receptor modulator (SERM), has estrogenic effects on bone and lipid metabolism but has minimal effects on uterine and breast tissue. It is beneficial in protecting againts osteoporosis and it does not cause vaginal bleeding
Menopause Transcutaneous Administration
Transdermal patches are available as unopposed estrogen form or as cyclical or continous estrogen progestogen combinations.
Advantage: no gastrointestinal side-effects, and minimize the effects on hepatic production of both lipoproteins and coagulation factors.
Estradiol may be implanted in subcutaneous fat, usually in the lower abdomen, at interval of no less than 5-6 months.
include estradiol tablets, low dose eatradiol-releasing silastic ring pessaries, and estriol vaginal pessaries and vaginal cream. They are all useful in the treatment of atrophic vaginitis Risk and Side Effects
General: Nausea,Brest Tenderness, irregular bleeds, cholelithiasis, glucose tolerance impairment
Endometrial Carcinoma: Estrogen only therapy increases the risk of endometrial cancer by fourfold and should be used for women who have had hysterectomy (the risk is reduced to less than 1 with opposing therapy).The levonorgestrel-releasing intrauterine system (Mirena) protects the endometrium effectively when used in conjunction with estrogen only HRT in PMW. Risk and Side Effects
Breast Cancer: small increase in likelihood of having breast cancer with combined HRT after 5 years of use.
Venous Thromboembolic disease: Increased risk in the first year of HRT treatment. No risk after one year of use
Stroke: Significant increase in the likelihood of stroke in all age groups, although the impact is small in younger menopausal women as the baseline risk is very low.
Contraindications of Hormone treatment
Pregnancy, Thromboembolic disease, H/O recurrent venous thromboembolism, liver disease, undiagnosed vaginal bleed are all CI to HRT
Use of estrogen-containing HRT is widely considered to be CI following Breast Cancer, adv endometrial carcinoma.
Non hormonal drugs
> Vasomotor symptoms can be reduced by clonidine, which acts directly on the hypothalamus.
> Palpitations and tachycardia may be improved by beta-blockers
> sedatives, hypnotics and antidepressants may be helpful in the treatment of non-vasomotor symptoms
> Osteoporosis: First line treatment is bisphosphonate, and estrogen is used only for those where this is inappropriate
> In elderly women, supplemetation with Calcium, Calcitonin and Vit D reduces the risk of Hip fractures.