Climagest Review Article
Climagest (Estradiol Valerate and Norethisterone). Climagest is a hormonal replacement therapy drug approved for the treatment of menopausal and premenopausal syndromes. It is a combination drug which contains Estradiol Valerate (C18H24O2) and Norethisterone (C20H26O2).
Climagest generic (generic - what is it?)
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Among the three, estradiol is the most potent and most dominant naturally occurring estrogen. It is about ten times more potent than estrone and about eighty times more potent than estriol. Estradiol is active during the premenopausal years (the reproductive years), after which is replaced by estrone once menopause is reached. Estriol is most abundant during pregnancy.
As a woman progresses in life, the ovaries gradually decrease its production of estrogenic compounds. As a result, several changes occur – irregular periods, mood swings, hot flushes, night sweats, vaginal dryness and itching. Once menopause is reached, estrogen levels in the body have significantly declined, and development of menopausal syndromes occur, which includes vasomotor symptoms, vaginal dryness and urogenital atrophy, and certain disease states related to estrogen like osteoporosis and cardiovascular diseases. Estradiol is used to replenish the decreasing amounts of estrogen in the body, especially during menopause. It acts as a supplement in the body, alleviating the menopausal syndromes.
Use of Estradiol as Menopausal Hormone Therapy
Osteoporosis is a progressive bone disease that is characterized by a continuous decrease in bone mass. This bone deterioration predisposes a patient to an increased risk for bone fractures, which are sometimes lethal. Estrogen plays a vital role in this disease - this compound promotes bone formation and decrease bone resorption - counteracting bone deterioration (Prince et al., 1991; Belchetz, 1994). Osteoblasts (bone cells responsible for bone formation) are stimulated by estrogen, while osteoclasts (responsible for bone resorption) are inhibited.
Due to the decrease of estrogen levels during menopause, females become highly susceptible to osteoporosis. As such, estrogen replacement therapy with Estradiol is instituted. In fact, according to the studies of Rossouw et al. (2002) and Anderson et al. (2004), it is the most effective agent for prevention of bone fractures in women who have no history of osteoporosis.
Estrogen plays an important role in the vagina – keeps it moist. During menopause, women experiences loss of tissue lining the vagina and bladder, causing symptoms like dryness, itching, swelling of genital tissues, painful urination, urinary incontinence and dyspareunia (Robinson & Cardozo, 2003). Replenishment of estrogen levels with Estrdaiol is the best treatment for these symptoms.
There is an increased incidence of cardiovascular diseases in menopausal women. However, the role of estrogen in the treatment of this disease is still not certain. Though estrogen is known to have good lipoprotein profile (Darko, et al., 2000), promotes vasodilation (Sudhir, et al., 1995) and reduces atherosclerosis formation, its effectiveness is still not yet well established. In fact, studies made by Rossouw et al. (2002) and Grady et al. (2002) revealed that there is an increase in cardiovascular incidence; opposite to the claims of Labo (1990) that it has cardioprotective properties. It is thus not recommended to use estrogen to prevent and treat cardiovascular diseases associated with menopause.
According to Belchetz (1994), estrogen replenishment (for example, Estradiol) is the most efficacious treatment for hot flushes, cold sweats, sweating and paresthesias associated with vasomotor symptoms.
A progestogen is a class of hormones important in menstruation (by promoting growth of uterine lining), pregnancy and embryogenesis (prevents the embryo from being “aborted”). There are several kinds of progestogen; in humans, the most abundant type is progesterone.
Progesterone is the most abundant type of progestogen in humans. It is secreted by the corpus luteum in the ovaries. Progesterone structure contains 4 cyclic hydrocarbons, with an attached ketone at Carbon 3 and 20 and methyl group at Carbon 20. It has several functions in the body, which includes promotion of the growth of uterine lining for menstruation, helps the embryo implant in the uterus during pregnancy, and prepares the breast tissue for lactation. Other functions include increasing good lipoprotein in the body (Farish, 1991) and improve glycemic control (Darko, et al, 2000). Progesterone antagonizes the effects of estrogen in the endometrial lining. Estrogen, when left alone, promotes the growth of the endometrium; when left unchecked, may lead to endometrial cancer. Progesterone regulates this growth, reducing the risk of formation of cancer. Medically speaking, this is the reason for the combined use of estrogen and progesterone, which is referred to as combined hormone replacement therapy.
Norethisterone is the first orally active synthetic progesterone made. Though rarely used as a monotherapy, it has several medically approved uses: premenstrual and menopausal syndromes, irregular or painful menstruation, and prevention of uterine bleeding during surgical procedures.
Combined Hormonal Therapy
As mentioned, a progestogen like Norethisterone is added to an estrogen like Estradiol to prevent endometrial carcinoma. Aside from that, the combination of these two has been found to be highly effective due to their synergistic effects. In fact, combination therapy is recommended to treat menopausal syndrome (Belchetz, 1994).
Though Climagest is recommended because of its combination, estrogen-alone preparations may be sufficient for patients who have had a hysterectomy. Hysterectomy is a procedure in which the uterus has been removed. Thus, if there is no uterus, there will be no endometrium in which estrogen will stimulate; therefore, no risk of endometrial cancer.
There are several studies being conducted to determine if hormonal therapy using estradiol and norethisterone, such as Climagest, can be used to treat premenstrual syndromes. One study, made by Magos et al. (1986), proposed a model for the use of such combination. It was determined that postmenopausal symptoms were similar to premenstrual symptoms. If combination hormonal therapy can treat postmenopausal symptoms, these drugs can also treat premenstrual symptoms. In their study, they subjected postmenopausal women to norethisterone. They found that norethisterone was able to satisfactorily treat the symptoms of pain, concentration loss, behavioural changes, water retention, and negative effect, which could very well be a good foundation for the use hormonal therapy for premenstrual symptoms.
Health Concerns: Updates
Ovarian and Breast Cancer
Many studies are still on going to provide concrete evidence that there is a reason for concern regarding the use of hormone replacement therapy (HRT) such as Climagest and cancer, particularly breast and ovarian cancer. There are several studies have been released though, each with their own data to prove their claim.
In a review made by Bluming and Tavris (2009), they assessed several reports and studies regarding the risks of breast cancer and HRT use - National Institute of Health (2002) states a relative risk of 1.26; Women’s Healh Initiative reports of 1.24 risk (2003), and no risk (2004 and 2006); Swedish report (1989) of 4.4 risk (that was not statistically significant); Japanese study (2006) found that HRT lowers risks; and many more. After presenting all the studies, their conclusion was that the there is a valid risk for breast cancer with HRT, however these risks are very minimal.
With respect to ovarian cancer, the use of a HRT is considered a risk factor for this disease. In a meta analysis done by Greiser C., Greiser E. and Doren (2007), they found that estrogen and progestin combination like Climagest induces a 1.11 increased risk for ovarian cancer.
A common concern for hormonal therapy – whether for contraception or for menopause – is weight gain. Many women believe that they will gain weight after using such drug, and such choose other therapeutic options just to avoid of the said adverse effect.
In a systematic review made by Norman, Flight and Rees (1999), they have provided evidence that there is no weight gain with the use of a combination HRT such as Climagest. There is also no increase in the BMI associated with the use of such drug during menopause.
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Menopause and Premenstrual Syndrome relief agents
Climagest Review Article